Good lag screw holding power in trabecular bone of the femoral head is a requisite to achieve stability in the management of proximal femoral fractures. It has been demonstrated that insertion torque and pullout strength of lag screw are linearly correlated. Therefore, insertion torque measurement could be a method to estimate the achieved screw purchase. Manual perception is not reliable [1], but the use of an instrumented screwdriver would make the procedure feasible.

The aim of this study was to assess the accuracy achievable using the insertion torque as predictor of lag screw purchase.

Four different screw designs (two cannulated and two solid-core screws) were investigated in this study. Each screw was inserted into a block of trabecular bone tissue following a standardised procedure designed to maximise the experimental repeatability. The blocks of trabecular tissue were extracted from human as well as bovine femora to increase the range of bone mineral density.

The prediction accuracy was evaluated by plotting pullout strength versus insertion torque, performing a linear regression analysis and calculating the difference (as percentage) between predicted and measured values.

Insertion torque showed a strong linear correlation (coefficient of determination R²: 0.95–0.99) with the pullout strength of lag screw. However the prediction error in pullout strength estimation was greater than 40% for small values of insertion torque, decreasing down to 15% when the lag screw was driven into good quality bone tissue.

Measuring insertion torque can supply quantitative information about the achieved lag screw purchase. Since screw design and insertion procedure have been shown to affect both the insertion torque and the pullout strength [2], the prediction model must be screw-specific and determined, closely simulating the clinical procedure defined by the screw manufacturer. However, the surgeon must be aware that, even under highly repeatable experimental conditions, the prediction error was found to be high when small insertion torque was measured, i.e. when the screw was driven in low quality bone tissue. Therefore, insertion torque is not reliable in evaluating lag screw purchase in the management of proximal femur fracture of osteoporotic patients.

Tranexamic acid (TXA) is an antifibrinolytic that can prevent clot breakdown. Trauma patients often have coagulopathy which can cause mortality due to bleeding. The purpose of this review is to investigate the efficacy of TXA in reducing mortality in major trauma and secondly to look at patient's outcomes when using TXA in trauma.

Searches were performed in PUBMED, EMBASE and other databases for randomised controlled trials (RCT) and observational studies. The author searched for all relevant evidence on the use of TXA in major trauma. Relevant studies were assessed for quality using the Cochrane's Collaboration's tool for assessing risk of bias.

Eight relevant studies were identified from the search, 3 randomised controlled trials (RCTs) and 5 observational studies were identified. Five of the 8 studies found a significance in mortality with TXA use. Three showed TXA reduced mortality including the high quality level I evidence, CRASH 2 study. Three studies found no significance on mortality. There appears to be no increased risk of VOE with TXA however results from the studies varied. No study reported any adverse events due to TXA use. There does not appear to be any significant benefit of TXA use in TBI but a trend towards lower mortality. There is a role in paediatric trauma despite evidence from only 2 observational studies.

There is a high quality RCT to suggest the use of TXA in trauma patients with supporting evidence from observational studies. The outcomes in TBI are unclear. It may be beneficial in paediatric use but there is currently no level 1 evidence in paediatrics to support this. Further prospective studies looking specifically at role in TBI and paediatric trauma are required to support routine use in these specific populations.

Most of researches related to osteoporosis emphasized on trabecular bone loss. However, cortical bone has a prominent role on bone strength determined by bone quality, such as 2D or 3D geometry and microstructure of bone, not only density.[1] The focal thinning of cortical bone associated with aging in post-menopausal osteoporotic bone in the proximal femur may predispose a hip to fracture.[2, 3] As the trabecular bone is lost with progression of osteoporosis, the remaining cortical bone take more predominant role on bone strength.[4] To date, no effective osteoporotic agent was demonstrated to enhance both cortical geometric change and bone strength. Herein, we investigate the effect of Teriparatide (rhPTH(1–34)) on cortical bone at femoral diaphysis in OVX rat model.

Twenty 12-week-old, female Sprague Dawley rats were used in this study. Bilateral ovariectomies were performed in 16 animals and randomly divided to three groups as control (N=6), OVX (N=6) and treatment group after OVX (OVX+F) by teriparatide (N=8). After twelve weeks of intervention, all rats were euthanized and right femurs and L5 vertebrae were extracted for further tests. All bone specimens were subjected to dual-energy X-ray absorptiometer (DXA) to evaluate areal bone mineral density (aBMD) of L5 vertebrae and femurs, micro-computed tomography (micro-CT) to analyze cortical bone parameters of femoral diaphysis, including cortical cross section area (CSA), cortical thickness and cross-sectional moment of inertia (CSMI). A three-point bending test was applied to determine fracture load of each femurs.

Compare to OVX group, increase of aBMD by 14.6 % at L5 vertebrae and 13.3% at femoral diahpysis in treatment group. The cortical parameters of femoral diaphysis, CSA and cortical thickness, analyzed by micro-CT were significantly increased but the increasing tendency of CSMI did not have significant changes statistically after teriparatide intervention for 3 months duration. The increase of cortical bone strength (OVX vs OVX+F group, 120.72±2.72 vs 137.93±5.02, p < 0.05) at femoral diaphysis after treatment were also noticed.

This study has point out a deeper look at geometric change of cortical bone after teriparatide treatment. This finding imply teirparatide has the ability to change the geometry of cortical bone and increase bone strength at femoral diaphysis.

Three Cannulated Screws (3CS), Dynamic Hip Screw (DHS) with antirotation screw (DHS–Screw) or with a Blade (DHS–Blade) are the gold standards for fixation of unstable femoral neck fractures. Compared to 3CS, both DHS systems require larger skin incision with more extensive soft tissue dissection while providing the benefit of superior stability. The newly designed Femoral Neck System (FNS) for dynamic fixation combines the advantages of angular stability with a less invasive surgical technique. The aim of this study is to evaluate the biomechanical performance of FNS in comparison to established methods for fixation of the femoral neck in a human cadaveric model.

Twenty pairs of fresh–frozen human cadaveric femora were instrumented with either DHS–Screw, DHS–Blade, 3CS or FNS. A reduced unstable femoral neck fracture 70° Pauwels III, AO/OTA31–B2.3 was simulated with 30° distal and 15° posterior wedges. Cyclic axial loading was applied in 16° adduction, starting at 500N and with progressive peak force increase of 0.1N/cycle until construct failure. Relative interfragmentary movements were evaluated with motion tracking.

Highest axial stiffness was observed for FNS (748.9 ± 66.8 N/mm), followed by DHS–Screw (688.8 ± 44.2 N/mm), DHS–Blade (629.1 ± 31.4 N/mm) and 3CS (584.1 ± 47.2 N/mm) with no statistical significances between the implant constructs. Cycles until 15 mm leg shortening were comparable for DHS–Screw (20542 ± 2488), DHS–Blade (19161 ± 1264) and FNS (17372 ± 947), and significantly higher than 3CS (7293 ± 850), p<0.001. Similarly, cycles until 15 mm femoral neck shortening were comparable between DHS–Screw (20846 ± 2446), DHS–Blade (18974 ± 1344) and FNS (18171 ± 818), and significantly higher than 3CS (8039 ± 838), p<0.001.

From a biomechanical point of view, the Femoral Neck System is a valid alternative to treat unstable femoral neck fractures, representing the advantages of a minimal invasive angle–stable implant for dynamic fixation with comparable stability to the two DHS systems with blade or screw, and superior to Three Cannulated Screws.

Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. Although age, blood pressure and infection are each considered to be prognostic factors in patients with SCI, exacerbating factors that are amenable to treatment remain to be elucidated.

Microglial cells, the resident immune cell in the CNS, form the first line of defense after being stimulated by exposure to invading pathogens or tissue injury. Immediately after SCI, activated microglia enhance and propagate the subsequent inflammatory response by expressing cytokines, such as TNF-α, IL-6 and IL-1β. Recently, we demonstrated that the activation of microglia is associated with the neuropathological outcomes of SCI. Although the precise mechanisms of microglial activation remain elusive, several basic research studies have reported that hyperglycemia is involved in the activation of resident monocytic cells, including microglia. Because microglial activation is associated with secondary injury after SCI, we hypothesized that hyperglycemia may also influence the pathophysiology of SCI by altering microglial responses.

The mice were anesthetized with pentobarbital (75 mg/kg i.p.) and were subjected to a contusion injury (70 kdyn) at the 10th thoracic level using an Infinite Horizons Impactor (Precision Systems Instrumentation). For flow cytometry, the samples were stained with the antibodiesand analyzed using a FACS Aria II flow cytometer and the FACSDiva software program (BD Biosciences). We retrospectively identified 528 SCI patients admitted to the Department of Orthopaedic Surgery at the Spinal Injuries Center (Fukuoka, Japan) between June 2005 and May 2011. The patients' data were obtained from their charts.

We demonstrate that transient hyperglycemia during acute SCI is a detrimental factor that impairs functional improvement in mice and human patients after acute SCI. Under hyperglycemic conditions, both in vivo and in vitro, inflammation was enhanced through promotion of the nuclear translocation of the nuclear factor kB (NF-kB) transcription factor in microglial cells. During acute SCI, hyperglycemic mice exhibited progressive neural damage, with more severe motor deficits than those observed in normoglycemic mice. Consistent with the animal study findings, a Pearson χ2 analysis of data for 528 patients with SCI indicated that hyperglycemia on admission (glucose concentration ≥126 mg/dl) was a significant risk predictor of poor functional outcome. Moreover, a multiple linear regression analysis showed hyperglycemia at admission to be a powerful independent risk factor for a poor motor outcome, even after excluding patients with diabetes mellitus with chronic hyperglycemia (regression coefficient, −1.37; 95% confidence interval, −2.65 to −0.10; P < 0.05). Manipulating blood glucose during acute SCI in hyperglycemic mice rescued the exacerbation of pathophysiology and improved motor functional outcomes.

Our findings suggest that hyperglycemia during acute SCI may be a useful prognostic factor with a negative impact on motor function, highlighting the importance of achieving tight glycemic control after central nervous system injury.

There has been evidence of association between femoral shaft fractures and prolonged bisphosphonate therapy. We present a case series of bisphosphonate-associated fractures and invaluable lessons we have learnt.

Over the last three years at our unit we have collected a case series of eight patients who have had atypical femoral fractures whilst on bisphosphonate therapy. We present illustrative cases, a summary of key findings, and invaluable lessons we have learnt.

There was a long period of prodromal pain for two years before incomplete fractures developed. We speculate this is a warning sign of impending fracture. This may have been prevented with screening. Between incomplete fracture and complete fracture there was a short window of one month. Five patients presented with complete fracture, and three with thigh pain +/- evidence of incomplete fracture. Of the latter group all but one went on to develop complete fractures. The one patient who did not progress died six years after diagnosis. Of those five patients who presented with initial complete fracture, three patients recall thigh pain before fracture on further questioning. Despite being diaphyseal femoral fractures, there is a higher risk of neck of femur fractures in this patient cohort (both patients with initial interlocked nails subsequently developed neck of femur fractures soon after and were revised to cephalomedullary nails). Excluding one death from unrelated cause, only one patient has signs of complete fracture healing. All other patients are still receiving follow-up (mean 490 days). Three patients reported bilateral symptoms (pain). Two had had bilateral symptoms for one year. Both had visible incomplete fractures on further radiographic scrutiny; one underwent prophylactic cephalomedullary nailing, one was managed with active surveillance.

We suggest that improved pain and radiographic changes of cortical healing may be misleading and should not be relied upon. Cephalomedullary nailing is the treatment of choice in these fractures due to higher risk of neck of femur fractures in this cohort. We suggest prompt prophylactic cephalomedullary nailing when radiographic incomplete fractures are identified due to a short window before progression to complete fracture, and the need to consider contralateral prophylactic nailing in patients describing bilateral symptoms. We speculate that thigh pain is a warning sign of impending fracture and fracture-progression can be prevented with appropriate screening.

To report the case of an asymptomatic simultaneous bilateral neck of femur fracture following vitamin D deficiency which was missed, misdiagnosed and treated for coexisting severe bilateral osteoarthritis knee.

A male aged 62 years presented with severe osteoarthritis of both knee joints confining him to bed about eight weeks prior to presentation. The patient did not have any complaints pertaining to his hip joints/axial skeleton. Examination of the hip joints revealed only crepitus with absence of straight leg rising. Radiological survey showed bilateral displaced fracture neck of femur. He had elevated serum alkaline phosphatase; 119IU/L(N:39–117IU/L), decreased Serum 25 (OH) Vit D level;6.03ng/ml(N:7.6–75ng/ml), decreased spot urinary calcium;78mg/day(N:100–300mg/day) with normal serum calcium, phosphorus and highly raised parathormone levels;142.51pg/ml(N:12–72pg/ml). Tc-99 Bone scan showed increased radiotracer uptake in both the hip joints and knee joints. Bone Mineral Density was in favour of osteoporosis. Biopsy fromthe heads of both femurs also revealed osteoporosis.

Bilateral staged total hip arthroplasty was done and he was put on Vitamin D replacement therapy. Patient was on regular monthly follow-up for intial one year and three monthly follow-up thereafter. At present with three year follow-up patient is community ambulant with a walking frame. Despite medical advice patient had denied total knee arthroplasty for osteoarthritis of his knee joints.

Asymptomatic simultaneous bilateral neck of femur fracture is a rare injury and poses a diagnostic challenge to the treating orthopaedic surgeon with its bizarre clinical picture. Similar presentation of metabolic bone disease can be easily missed without a proper screening, keeping in mind a high index of suspicion for the above disorders. Besides proper clinical examination of both hip and knee joint should be performed in patients presenting with bilateral knee pain. A good functional outcome may be achieved with prompt surgical intervention and medical treatment.

The influence of rigid fixation and permanent compression on the results, the timing of fusion and rehabilitation after fractures of the femoral neck was investigated.

A hip fracture is 60–80% of all fractures of the proximal femur. Despite recent advances in the treatment of this disease, the percentage of unsatisfactory outcomes as high as 25–35%. The choice of surgical treatment in femoral neck fractures in the elderly remains as controversial as it was almost 50 years ago when Speed called him as “the unsolved fracture. Hip replacement is currently the gold standard in the treatment of femoral neck fractures. But compared with the osteosynthesis operation takes more time, is accompanied by massive blood loss, sometimes the need for transfusion and a higher risk of deep wound infection. Given these facts the best is an indoor low-traumatic method of osteosynthesis locking.

Compare of the results of femoral neck fractures using of osteosynthesis 3 blade nail, spongious screws and nail for permanent compression.

A retrospective analysis of treatment of 252 patients from 1982 to 2015 with subcapitale and transcervical fractures of the femoral neck on the basis “RCTO named by H.J. Makazhanova”. In the research locales patients older than 40 years. All patients were divided according to the applied method of treatment: 1 group of 95 patients operated using a 3-blade-nail, in the 2nd group of 105 patients operated on spongious screws, in the 3 group of 52 patients operated nail for the permanent compression, authoring. All patients underwent x-ray examination before and after surgery. The average period from time of injury before performing the osteosynthesis amounted to 4–7 days. The follow-up period was 6–12 months. The results obtained clinically and radiographically divided into good, satisfactory, poor. Good and satisfactory results were regarded as positive, and poor results as negative.

The average age of patients was 67.5 years. Among these female patients − 174 (69%), the male − 78 (31%). Traumatization more prone to elderly accounting for 206 (81.7%) cases, and only 46 (18.3%) in the middle age group. Analysis of the results of treatment showed positive results in 1 group − 69.5 %, in group 2 − 83.8 %, in group 3 − 96.2 %. In the first group of 29 (31.5 %) and in the second group of 17 (16.2 %) patients have postoperative complications: secondary displacement, nail migration, pseudarthrosis, necrosis of head. The patients of third group have postoperative complications in 2 cases (3.8 %): displacement of bone fragments according of retraumatization. Employability was restored in 1 group − 7–9 months, in group 2 - in 6–8 months, 3 group - through 6–6.5 months.

1)

The method of choice for fresh fractures of the femoral neck, especially subcapital fractures in the elderly, is a minimally invasive method of closed compression osteosynthesis.

Femoral head collapse is a possible complication after surgical treatment of femoral neck fractures. The purpose of this study was to examine whether implantation of a Sliding Hip Screw (SHS) or an X-Bolt could increase the risk of femoral head collapse. Similar to traditional hip screws, the X-Bolt is implanted through the femoral neck; however, it uses an expanding cross-shape to improve rotational stability. The risk of collapse was investigated alongside patient factors, such as osteonecrosis.

This numerical study assessed the risk of femoral head collapse using linear eigenvalue buckling (an established method [1]), and also from the maximum von Mises stress within the cortical bone. The femoral head was loaded using the pressures reported by Yoshida et al. for a patient sitting down (reported to put the femoral head at greatest risk of collapse [2]), with a peak pressure of 9.4 MPa and an average pressure of 1.59 MPa. The femur was fixed in all degrees of freedom at a plane through the femoral neck. The X-Bolt and SHS were implanted in accordance with the operative techniques. The femoral head and implants were meshed with quadratic tetrahedral elements, and cortical bone was meshed with triangular thin shell elements. A converged mesh seeding density of 1.2 mm was used. All models were create and solved using ABAQUS finite element software (version 6.12, Simulia, Dassault Systèmes, France). The influence of implant type and presence was examined alongside a variety of patient factors:

Osteonecrosis, modelled as a cone of bone of varying angle, and varying modulus values

Twenty-two finite element models were run for each implant condition (intact; implanted with the X-Bolt; implanted with a SHS), resulting in a total of 66 models. The finite element models were validated using experimental tests performed on five 4^th generation composite Sawbones femurs (Malmö, Sweden), and verified against previously published results [1].

No significant difference was found between the X-Bolt and the SHS, for either critical buckling pressure (p=0.964), or the maximum von Mises stress (p=0.274), indicating no difference in the risk of femoral head collapse. The maximum von Mises stress (and therefore the risk of collapse) within the cortical bone was significantly higher for the intact femoral head compared to both implants (X-Bolt: p=0.048, SHS: p=0.002). Of the factors examined, necrosis of the femoral head caused the greatest increase in risk.

The study by Volokh et al. [1] concluded that deterioration of the cancellous bone underneath the cortical shell can greatly increase the risk of femoral head collapse, and the results of the present study support this finding. Interestingly the presence of either an X-Bolt or SHS implant appeared to reduce the risk of femoral head collapse.

Osteoporosis is an international health and financial burden of ever increasing proportions. Current treatments limit the rate of bone resorption and reduce fracture risk, however they are often associated with significant and debilitating side effects. The most commonly used therapies also do not stimulate osteoblast activity ^1,2,3. Much current research focus is aimed at the metabolic and epigenetic pathways involved in osteoporosis. MicroRNAs have been shown to play an important role in bone homeostasis and pathophysiological conditions of the musculoskeletal system. Up-regulation of specific microRNAs has been identified in-vivo in osteoporotic patients ^4,5. It is hypothesized that modulation of specific microRNA expression may have a key role in future targeted therapies of musculoskeletal diseases. The assessment and analysis of their potential therapeutic use in Osteoporosis is of great importance, due to the burden of the disease.

We have developed a 3D osteoporotic model from human bone marrow, without the use of scaffold. Magnetic nanoparticles are utilised to form spheroids, which provides a closer representation of the in-vivo environment than monolayer culture. This model will provide the basis for analysing future microRNA experiments to assess the potential up-regulation of osteoblastogenesis without cessation of osteoclast activity.

The results of initial monolayer and spheroid experiments will be presented. Optimisation of the osteoporotic bone marrow culture conditions, involving response to differentiation medias, analysis of adipose and bone markers and cell migration in spheroid culture will be displayed. Quantitative and qualitative results, including fluorescence microscopy and in cell western, assessing the monolayer and spheroid cultures will be presented. The development of a pseudo osteoporosis model from healthy bone marrow will also be discussed. This model will form a basis of future work on microRNA targeting.

The development of improved therapies for osteoporosis is of great significance due to the predicted rise in incidence of the disease and associated fragility fractures. Targeted therapies, such as the manipulation of microRNA expression, offer the opportunity to increase osteoblastogenesis and decrease osteoclastogenesis, potentially without the associated side effects of older, systemic therapies. We believe our 3D human bone marrow derived osteoporotic model offers the closest relation to the in-vivo environment for assessment and manipulation of microRNA expression.

Delayed bone healing and nonunion are complications of long bone fractures, with prolonged pain and disability. Regenerative therapies employing mesenchymal stromal cells (MSC) and/or bone substitutes are increasingly applied to enhance bone consolidation. The REBORNE project entailed a multi-center orthopaedic clinical trial focused on the evaluation of efficacy of expanded autologous bone marrow (BM) derived MSC combined with a CaP-biomaterial, to enhance bone healing in patients with nonunion of diaphyseal fractures. To complement the clinical and radiological examination of patients, bone turnover markers (BTM) were assayed as potential predictors of bone healing or non-union.

Peripheral blood was collected from patients at fixed time-endpoints, that is at 6,12 and 24 weeks post-surgery for implantation of expanded autologus MSC and bone-like particles. Bone-specific alkaline phosphatase (BAP), C-terminal-propeptide type I-procollagen (PICP), osteocalcin (OC), β-Cross-Laps Collagen (CTX), soluble receptor activator of NFkB (RANKL), osteoprotegerin (OPG) were measured by ELISA assays in blood samples of 22 patients at BM collection and at follow-up visits.

A significant relationship with age was found only at 6 months, with an inverse correlation for CTX, RANKL and OC, and positive for OPG. BTM levels were not related to gender. As an effect of local regenerative process, some BTM showed significant changes in comparison to the baseline value. In particular, the time course of BAP, PICP and RANKL was different in patients with a successful healing in comparison to patients with a negative outcome. The BTM profile apparently indicated a remarkable bone formation activity 12 weeks after surgery. However, the paucity of failed patients in our case series did not allow to prove statistically the role of BTM as predictors of the final outcome.

Blood markers related to bone cell function are useful to measure the efficacy of a expanded MSC-regenerative approach applied to long bone non-unions. Changes of the markers may provide a support to radiological assessment of bone healing.

Hip fractures constitute the most debilitating complication of osteoporosis with a steadily increasing incidence in an aging population. Intramedullary nailing of osteoporotic proximal femoral fractures can be challenging because of poor implant anchorage in the femoral head. Recently, cement augmentation of PFNA blades with Polymethylmethycrylate (PMMA) has shown promising results by enhancing the cutout resistance in proximal femoral fractures. The aim of this biomechanical study was to assess the impact of cement augmentation on the fixation strength of TFNA blades and screws within the femoral head, and compare its effect with head elements placed in a center or antero–posterior off–center positions.

Eight groups were formed out of 96 polyurethane foam specimens with low density, simulating isolated femoral heads with severe osteoporotic bone. The specimens in each group were implanted with either non–augmented or PMMA–augmented TFNA blades or screws in a center or antero–posterior off–center position, 7 mm anterior or 7 mm posterior. They were mechanically tested in a setup simulating an unstable pertrochanteric fracture with lack of postero–medial support and load sharing at the fracture gap. All specimens underwent progressively increasing cyclic loading until catastrophic construct failure. Varus–valgus and head rotation angles were monitored by an inclinometer mounted on the head. A varus collapse of 5° or a 10° head rotation were defined as the clinically relevant failure criterion.

Load at failure for specimens with augmented TFNA head elements (screw center: 3799 N ± 326 (mean ± SD); blade center: 3228 N ± 478; screw off–center: 2680 N ± 182; blade off–center: 2591 N ± 244) was significantly higher compared to the respective non–augmented specimens (blade center: 1489 N ± 41; screw center: 1593 N ± 120; blade off–center: 1018 N ± 48; screw off–center: 515 N ± 73), p<0.001. In both non–augmented and augmented specimens, the failure load in center position was significantly higher compared to the respective off–center position, regardless of head element, p<0.001. Non–augmented TFNA blades in off–center position revealed significantly higher load at failure versus non–augmented screws in off–center position, p<0.001.

Cement augmentation clearly enhances fixation stability of TFNA blades and screws. Non–augmented blades outperformed screws in antero–posterior off–center position. Positioning of TFNA blades in the femoral head is more forgiving than TFNA screws in terms of failure load. Augmentation with TFNA has not been approved by FDA.

The development and introduction of the closed locked intramedullary nail into clinical practice has revolutionized the treatment of fractures of long bone. The most difficult and technically demanding part of the procedure is often the insertion of the distal interlocking screws. A lot of efforts have been made during the past years to make it easier. In according with Whatling and Nokes, we can divide the different approaches to this issue in four main groups:

Free-hand (FH) technique;

In addition of these, recently it has been proposed a navigational system using electromagnetic field.

The main disadvantages of the FH technique, are prolonged exposure to radiation and results depend mostly on the dexterity of the surgeons. FH technique is however the most popular technique.

Our targeting device is included into the mounted on image intensifier group. It consists of 2 radio-opaque rods at right angle to each over: one of this is fixed on the c-arm, whereas, the other is a sliding rod with a sleeve for the drill bit, which is the targeting guide itself. In the realization of this device, we have been inspired by the modification of the FH technique suggested by Kelley et al. To identify the distal holes we used the method described by Medoff (perfect circle). Once that the distal hole is seen as a perfect circle, with the C-arm in later view, the targeting guide is roughly positioned onto this and the drilling and the screwing operations are performed without the need for image intensifier. We used the device in bone models and in 9 clinical cases.

In spite of authors demonstrated that the electromagnetic targeting device significantly reduced radiation exposure during placement of distal interlocking screws and was equivalent in accuracy when compared with the FH technique, the latter is the most used technique. Indeed, although all the studies have reported that the radiation exposure to orthopedic surgeon has been below the maximum allowable doses in all cases, there is still the risk of cumulative lifetime radiation exposure. From this point of view, namely the reduction of cumulative lifetime radiation exposure, we think that, paradoxically, our device could be more effective than electromagnetic targeting device, because it can be used in all the orthopedic operations that required a targeting device.

Previous studies have shown that Tnmd is important for tendon maturation and has key implications for the residing tendon stem/progenitor cells. The putative signaling in which Tnmd participates is just starting to be better understood (Dex et al. 2016). However, its exact functions during tendon healing process still remain elusive. Therefore, the aims of this study were to perform systematic review of the literature on Tnmd-related research and to investigate the role of Tnmd in early tendon healing by applying a tendon rupture model in Tnmd-deficient mice.

First, we searched in the PubMed database for articles containing “tenomodulin” or its alternative names and abbreviations. After exclusion of papers only available in abstract form and foreign language, we grouped the remaining 128 full-text publications into four study types: 1) looking into functions of Tnmd; 2) using Tnmd as a tendon marker; 3) correlating Tnmd mutations to a variety of diseases; and 4) reviews. Following literature analysis, we carried out a pilot Achilles tendon injury model with Tnmd-knockout (KO) mouse strain. Adult Tnmd-KO (n = 8) and wild-type (WT) (n = 8) mice underwent unilateral surgery of Achilles tendon based on Palmes et al. 2002 and were compared at day 8 postoperatively by: 1) H&E staining for overall assessment; 2) immunohistochemical BrdU analysis for cell proliferation; and 3) Safranin O staining for endochondral formation.

Our literature screen revealed that Tnmd has been strongly justified as the best tendon and ligament marker in more than 90 different studies. Moreover, in vivo and in vitro investigations have demonstrated its positive role on tendon cell proliferation and tissue functions. Our follow up surgical study showed a very different scar organization in Tnmd-KO with a clearly reduced cell density. BrdU analysis confirmed a lower number of proliferating cells in Tnmd-KO scar area. Interestingly, endochondral formation was not observed in the scar tissues in either of the genotypes at day 8.

Taken together, we systematically summarized the current knowledge on Tnmd gene and highlighted several future research perspectives. Lack of studies on the role of Tnmd in tissue healing, motivated our pilot investigation on Achilles tendon rupture, which in turn suggested that loss of Tnmd results in inferior repair process.

The exact pathways of collagen remodeling in tendon tissue are not well understood. Therefore, we have established an ex vivo 3D collagen gel-based system and we studied the remodeling capacity of two different TSPC lines from young, Y-TSPC and aged/degenerative, A-TSPC donors. Here, we specifically focused on investigating the involvement of integrin receptors in the remodeling process. Integrins are transmembrane receptors consisting of alpha (a) and beta (b) subunits, which form cell-to-matrix bonds, activate various pathways and thereby control cell proliferation, differentiation and survival.

Y- and A-TSPC were derived from human Achilles tendons and are fully described in Kohler et al. 2013. RT-PCR was used to assess the expression of collagen-binding integrins in the TSPC cultivated in collagen gels. Next, a1 and a11 integrins were silenced by stable lentiviral delivery of target-specific shRNA in the Y-TSPC. Control (con-shRNA), integrin (a1-shRNA) and integrin a11 (a11-shRNA) virus-containing supernatant was given for 24h and then cells were selected with 50 microg./ml zeocin for 10 days. The integrin knockdown (KD) efficiency was assessed by quantitative PCR and western blotting. Last, functional tests were carried out by time-lapse recording gel contraction of four cell groups (Y-TSPC+con, Y-TSPC+a1KD, Y-TSPC+a11KD, and A-TSPC).

Among the screened integrins we found that integrin a1 and a11 were significantly downregulated in A-TSPC with 3.8 and 5.6 folds, correspondingly. Therefore, to mimic the A-TSPC we carried out a gene KD of a1 and a11 in Y-TSPC. PCR and western blot clearly validated the efficient KD. Analyses of collagen contraction, revealed that Y-TSPC+a11KD significantly reduced collagen contractability comparable to A-TSPC. This indicated the indispensable role of this integrin in the signaling pathway of collagen matrix remodeling. In respect to integrin a1, we found that this receptor did not affect the contraction rate of Y-TSPC, which was similar to Y-TSPC+con.

To our knowledge we have now identified for the first time the critical role of a11 integrin receptor in tendon collagen remodeling, and a follow up analysis of its exact downstream cascade is on the way. Future efforts in deciphering how tendon matrix makeover is regulated can lead to innovation in preventive strategies for tendon degeneration.

Achilles tendon rupture may lead to significant functional deficits, which mechanisms are poorly understood. The primary aim was to investigate if the Achilles tendon (AT) was longer, muscles weaker or gait changed on the injured leg 4–5 years after the injury. Secondary aim was to compare functional outcomes with patient reported Achilles Tendon Total Rupture Score (ATRS).

We invited all participants from an RCT of conservatively treated AT Rupture (ATR) with or without early weight-bearing (early-WB, non-WB), and 12 moths of follow up. Of the original 56, 37 patients participated, 19 from early-WB (1 re-rupture (RR)), and 18 from non-WB (2 RR). Time from injury to follow up was 4,5 years (4,1 to 5,1). AT length was measured using ultrasound with a validated protocol (Barfod K.W. et al.). Heel raise work was measured on a 10 degree inclining platform. The exercise lasted until the patient could not maintain frequency or height of lift. Number and height of lift was measured using reflective markers in a Vicon system, and total work calculated. Foot pressure mapping (FPM) was measured barefoot, using an EMED platform (novel, Germany). Statistics: T-test for limb to limb comparisons and linear regression for ATRS correlations was applied.

Including RR in the sample did not impact the results. We found no differences in any of the variables between the early-WB and non-WB groups. Compared to the uninjured limb, the Achilles tendon was an average of 1,8 (1,2–2,3) cm longer on the injured limb, which produced 40% less work. A smaller calf circumference (p < 0.001), larger dorsiflextion (p = 0.001), and Achilles tendon resting angle (p < 0.001) was found for the injured limb. Difference in mean medial forefoot peak pressure was approaching significance (healthy 484 (SD 165) KPa, injured: 439 (SD 160), p = 0.08). Similarly the difference in pressure / time integral of the medial forefoot was approaching significance (Healthy: 129 (SD 35)KPa, injured: 115 (SD 44)KPa, p = 0.08). Duration of contact time of the heel was extended and heel lift off was delayed in the injured limb (p = 0.02 for both). ATRS could not be linked to Achilles tendon length or total work using linear regression.

Conservatively treated Achilles tendon ruptures were approximately 1,8 cm longer. The limb was persistently weaker. A subtle change in heel contact duration and time of heel rise could be detected on the injured limb. ATRS does not appear to correlate directly with AT length or loss of total work.

Tendinopathies represent the 45% of the musculoskeletal lesions and they are a big burden in clinics. Indeed, despite the relevant social impact, both the pathogenesis and the development of the tendinopathy are still under-investigated, thus limiting the therapeutic advancement in this field. Indeed, current treatment for tendinopathy are mainly symptomatic, and they present a high rate of pathology re-occurrence. In this contest, the development of an efficient in vivo model of acute tendinopathy, focused on the choice of the most appropriate species and strategy to induce the disease, would allow a better understanding of the pathology progression throughout its phases.

Then, the purpose of this study was to evaluate the dose-dependent and time-related tissue-level changes occurring in a collagenase-induced tendinopathy in rat Achilles tendons, in order to establish a standardized model for future pre-clinical studies.

40 Sprague Dawley rats were randomly divided into two groups, treated by injection of collagenase type I within the Achilles tendon at 1 mg/mL (low dose, LD) or 3 mg/mL (high dose, HD). Tendon explants were histologically evaluated at 3, 7, 15, 30 and 45 days by H&E staining.

Our results showed that both the collagenase doses induced a disorganization of collagen fibers and increased the number of rounded resident cells. In particular, the high dose treatment determined a greater fatty degeneration and neovascularization with respect to the lower dose. These changes are time-dependent, thus resembling the tendinopathy development in humans. Indeed, the acute phase occurred from day 3 to day 15, while from day 15 to 45 it progressed towards the proliferative phase, displaying a degenerative appearance associated with a precocious remodeling process.

The model represents a good balance between feasibility, in terms of reproducibility and costs, and similarity with the human disease. Moreover, the present model contributes to improve the knowledge about tendinopathy development, and then it could be useful to design further pre-clinical studies, in particular in order to test innovative treatments for tendinopathy.

DVC allowed measurements of displacement and strain distribution in bone through the comparison of two, or more, 3D images. Hence, it has a potential as a diagnostic tool in combination with clinical CT. Currently, traditional computed tomography (CT) allows for a detailed 3D analysis of hard tissues, but imaging in a weight-bearing condition is still limited. PedCAT-CT (Curvebeam, USA) emerged as a novel technology allowing, for the first time, 3D imaging under full-weight bearing (Richter, Zech et al. 2015). Specifically, a PedCAT-CT based DVC was employed to establish its reliability through the strain uncertainties produced on bone structure targets, preliminarily to any further clinical studies. In addition, a reverse engineering FE modeling was used to predict possible force associated to displacement errors from DVC.

Three porcine thoracic vertebrae were used as bone benchmark for the DVC (Palanca, Tozzi et al. 2016, Tozzi, Dall'Ara et al. 2016). The choice of using porcine vertebrae (in a CT designed for foot/ankle) was driven by availability, as well as similar dimensions to the calcaneus. Each vertebra was immersed in saline solution and scanned twice without any repositioning (zero-strain-test) with a pedCAT-CT (Curvebeam, USA) obtaining an isotropic voxel size of 370 micrometers. Volumes of interest of 35 voxel were cropped inside the vertebrae. Displacement and strains were evaluated using DVC (DaVis-DC, LaVision, Germany), with different spatial resolution. The displacement maps were used to predict the force uncertainties via FE (Ansys Mechanical v.14, Ansys Inc, Canonsburg, PA). Each element was assigned a linear elastic isotropic constitutive law (Young modulus: 8 GPa, Poisson's ratio: 0.3, as in (Follet, Peyrin et al. 2007)). Overall, the precision error of strain measurement was evaluated as the average of the standard deviation of the absolute value of the different component of strain (Liu and Morgan 2007).

The force uncertainties obtained with the FE analysis produced magnitudes ranging from 231 to 2376 N. No clear trend on the force was observed in relation to the spatial resolution. Precision errors were smaller than 1000 microstrain in all cases, with the lowest ranging from 83 microstrain for the largest spatial resolution. Full-field strain on the bone tissue did not seem to highlight a preferential distribution of error in the volume.

The precision errors showed that the pedCAT-CT based DVC can be sufficient to investigate the bone tissue failure (7000–10000 microstrain) or, physiological deformation if well-optimized. FE analysis produced important force uncertainties up to 2376 N. However, this is a preliminary investigation. Further investigation will give a clearer indication on DVC based PedCAT-CT, as well as force uncertainties predicted. So far, the DVC showed its ability to measure displacement and strain with reasonable reliability with clinical-CT as well.

In podiatric medicine, diagnosis of foot disorders is often merely based on tests of foot function in static conditions or on visual assessment of the patient's gait. There is a lack of tools for the analysis of foot type and for diagnosis of foot ailments. In fact, static footprints obtained via carbon paper imprint material have traditionally been used to determine the foot type or highlight foot regions presenting excessive plantar pressure, and the data currently available to podiatrists and orthotists on foot function during dynamic activities, such as walking or running, are scarce.

The device presented in this paper aims to improve current foot diagnosis by providing an objective evaluation of foot function based on pedobarographic parameters recorded during walking.

23 healthy subjects (16 female, 7 males; age 35 ± 15 years; weight 65.3 ± 12.7; height 165 ± 7 cm) with different foot types volunteered in the study. Subjects' feet were visually inspected with a podoscope to assess the foot type. A tool, comprised of a 2304-sensor pressure plate (P-walk, BTS, Italy) and an ad-hoc software written in Matlab (The Mathworks, US), was used to estimate plantar foot morphology and functional parameters from plantar pressure data. Foot dimensions and arch-index, i.e. the ratio between midfoot and whole footprint area, were assessed against measurements obtained with a custom measurement rig and a laser-based foot scanner (iQube, Delcam, UK).

The subjects were asked to walk along a 6m walkway instrumented with the pressure plate. In order to assess the tool capability to discriminate between the most typical walking patterns, each subject was asked to walk with the foot in forcibly pronated and supinated postures. Additionally, the pressure plate orientation was set to +15°, +30°, −15° and −30° with respect to the walkway main direction to assess the accuracy in measuring the foot progression angle (i.e. the angle between the foot axis and the direction of walk). At least 5 walking trials were recorded for each foot in each plate configuration and foot posture.

The device allowed to estimate foot length with a maximum error of 5% and foot breadth with an error of 1%. As expected, the arch-index estimated by the device was the lowest in the cavus-feet group (0.12 ± 0.04) and the highest in the flat-feet group (0.29 ± 0.03). These values were between 4 – 10 % lower than the same measurements obtained with the foot scanner. The centre of pressure excursion index [1] was the lowest in the forcibly-pronated foot and the largest in the supinated foot.

While the pressure plate used here has some limitations in terms of spatial resolution and sensor technology [2], the tool appears capable to provide information on foot morphology and foot function with satisfying accuracy. Patient's instrumental examination takes only few minutes and the data can be used by podiatrists to improve the diagnosis of foot ailments, and by orthotists to design or recommend the best orthotics to treat the foot condition.

Knee ligament injury is one of the most frequent sport injuries and ligament reconstruction has been used to restore the structural stability of the joint. Cycling exercises have been shown to be safe for anterior cruciate ligament (ACL) reconstruction and are thus often prescribed in the rehabilitation of patients after ligament reconstruction. However, whether it is safe for posterior cruciate ligament (PCL) reconstruction remains unclear. Considering the structural roles of the PCL, backward cycling may be more suitable for rehabilitation in PCL reconstruction. However, no study has documented the differences in the effects on the knee kinematics between forward and backward pedaling. Therefore, the current study aimed to measure and compare the arthrokinematics of the tibiofemoral joint between forward and backward pedaling using a biplane fluoroscope-to- computed tomography (CT) registration method.

Eight healthy young adults participated in the current study with informed written consent. Each subject performed forward and backward pedaling with an average resistance of 20 Nm, while the motion of the left knee was monitored simultaneously by a biplane fluoroscope (ALLURA XPER FD, Philips) at 30 fps and a 14-camera stereophotogrammetry system (Vicon, OMG, UK) at 120 Hz. Before the motion experiment, the knee was CT and magnetic resonance scanned, which enabled the reconstruction of the bones and articular cartilage. The bone models were registered to the fluoroscopic images using a volumetric model-based fluoroscopy-to-CT registration method, giving the 3-D poses of the bones. The bone poses were then used to calculate the rigid-body kinematics of the joint and the arthrokinematics of the articular cartilage. In this study, the top dead center of the crank was defined as 0° so forward pedaling sequence would begin from 0° to 360°.

Compared with forward pedaling, for crank angles from 0° to 180°, backward pedaling showed significantly more tibial external rotation. Moreover, both the joint center and contact positions in the lateral compartment were more anterior while the contact positions in the medial compartment was more posterior, during backward pedaling. For crank angles from 180° to 360°, the above-observed phenomena were generally reversed, except for the anterior-posterior component of the contact positions in the medial compartment.

Forward and backward pedaling displayed significant differences in the internal/external rotations while the rotations in the sagittal and frontal planes were similar. Compared with forward cycling, the greater tibial external rotation for crank angles from 0° to 180° during backward pedaling appeared to be the main reason for the more anterior contact positions in the lateral compartment and more posterior contact positions in the medial compartment.

Even though knee angular motions during forward and backward pedaling were largely similar in the sagittal and frontal planes, significant differences existed in the other components with different contact patterns. The current results suggest that different pedaling direction may be used in rehabilitation programs for better treatment outcome in future clinical applications.

The study aimed to compare trochlear profiles in recent total knee arthroplasty (TKA) models and to determine whether they feature improvements compared to their predecessors. The hypothesis was that recent TKA models have more anatomic trochlear compartments and would display no signs of trochlear dysplasia.

The authors analyzed the geometry of the 6 following TKA models using engineering software: PFC and Attune (DePuy), NexGen and Persona (Zimmer), Noetos and KneeTec (Tornier). The mediolateral trochlear profiles were plotted at various flexion angles (0°, 15°, 30° and 45°) to deduce the sulcus angle.

Analysis of sulcus angles reveals general convergence of recent designs towards anatomic values. At 0° of flexion, sulcus angles of recent implant models were between 156.0–157.4°, while those of previous generation models between 154.5–165.5°. At 30° of flexion, sulcus angles of recent models also lie within 145.7–148.6°, but those of previous models are between 149.5–152.0°. All three manufacturers deepened their trochlear profile at 30° of flexion in recent models compared to earlier designs. Sulcus angles converge towards anatomic values but still exceed radiologic signs of dysplasia by 2–5°.

Recent TKA designs have more anatomic trochlear geometries than earlier TKA models by the same manufacturers, but trochlear compartments still exceed radiologic signs of trochlear dysplasia by 2° to 5°. The hypothesis that recent TKA models display no signs of trochlear dysplasia is therefore refuted. Surgeons should be aware of design limitations to optimize choice of implant and extensor mechanisms alignment. Level of evidence: IV geometric implant analysis.

The current, most popular recommendation for cup orientation, namely the Lewinnek box, dates back to the 70's, that is to say at the stone age of hip arthroplasty. Although Lewinnek's recommendations have been associated with a reduction of dislocation, some complications, either impingement or edge loading related, have not been eliminated. Early dislocations are becoming very rare and most of them probably occur in “outlier” patients with atypical pelvic/hip kinematics. Because singular problems usually need singular treatments, those patients need a more specific personalised planning of the treatment rather than a basic systematic application of Lewinnek recommendations. We aim in this review to define the potential impacts that the spine-hip relations (SHRs) have on hip arthroplasty. We highlight how recent improvements in hip implants technology and knowledge about SHRs can substantially modify the planning of a THR, and make the « Lewinnek recommendations » not relevant anymore. We propose a new classification of the SHRs with specific treatment recommendations for hip arthroplasty whose goal is to help at establishing a personalized planning of a THR. This new classification gives a rationale to optimize the short and long-term patient's outcomes by improving stability and reducing edge loading. We believe this new concept could be beneficial for clinical and research purposes.

The purpose of this study is to investigate the three-dimensional (3D) kinematics of normal knees in deep knee-bending motions like squatting and kneeling.

Material & Methods: We investigated the in vivo kinematics of 4 Japanese healthy male volunteers (8 normal knees in squatting, 7 normal knees in kneeling). Each sequential motion was performed under fluoroscopic surveillance in the sagittal plane. Femorotibial motion was analyzed using 2D/3D registration technique, which uses computer-assisted design (CAD) models to reproduce the spatial position of the femur and tibia from single-view fluoroscopic images. We evaluated the femoral rotation relative to the tibia and anteroposterior (AP) translation of the femoral sulcus and lateral epicondyle on the plane perpendicular to the tibial mechanical axis. Student's t test was used to analyze differences in the absolute value of axial rotation and AP translation of the femoral sulcus and lateral epicondyle during squatting and kneeling. Values of P < 0.05 were considered statistically significant.

During squatting, knees were gradually flexed from −2.8 ± 1.3° to 145.5 ± 5.1° on average. Knees were gradually flexed from 100.8 ± 3.9° to 155.6 ± 3.2° on average during kneeling. Femurs during squatting displayed sharp external rotation relative to the tibia from 0° to 30° of flexion and it reached 12.5 ± 3.3° on average. From 30° to 130° of flexion, the femoral external rotation showed gradually, and it reached 19.1 ± 7.3° on average. From 130° to 140° of flexion, it was observed additionally, and reached 22.4 ± 6.1° on average. All kneeling knees displayed femoral external rotation relative to the tibia sharply from 100° to 150° of flexion, and it reached 20.7 ± 7.5° on average. From 100° to 120° of flexion, the femoral external rotation during squatting was larger than that during kneeling significantly. From 120° to 140° of flexion, there was no significant difference between squatting and kneeling. The sulcus during squatting moved 4.1 ± 4.8 mm anterior from 0° to 60° of flexion. From 60° of flexion it moved 13.6 ± 13.4 mm posterior. The sulcus during kneeling was not indicated significant movement with the knee flexion. The lateral epicondyle during squatting moved 39.4 ± 7.7 mm posterior from 0° to 140° of flexion. The lateral epicondyle during kneeling moved 22.0 ± 5.4 mm posterior movement from 100° to 150° of flexion. In AP translation of the sulcus from 100° to 140° of flexion, there was no significant difference between squatting and kneeling. However in that of the lateral epicondyle, squatting groups moved posterior significantly.

Even if they were same deep knee-bending, the kinematics were different because of the differences of daily motions. The results in this study demonstrated that in vivo kinematics of deep knee-bending were different between squatting and kneeling.

Total shoulder arthroplasty is a well-tested procedure that offers pain relief and restores the joint function. However, failure rate is still high, and glenoid loosening is pointed as the main reason in orthopedic registers. In order to understand the principles of failure, the principal strain distributions after implantation with Comprehensive® Total Shoulder System of Biomet® were experimental and numerically studied to predict bone behavior.

Fourth generation composite left humerus and scapula from Sawbones® were used. These were implanted with Comprehensive® Total Shoulder System (Biomet®) with a modular Hybrid® glenoid base and Regenerex® glenoid and placed in situ by an experienced surgeon. The structures were placed in order to simulate 90º abduction, including principal muscular actions. Muscle forces used were as follows: Deltoideus 300N, Infraspinatus 120N, Supraspinatus 90N, Subscapularis 225N.

All bone structures were modeled considering cortical and the trabecular bone of the scapula. The components of prosthesis were placed in the same positions than those in the in vitro models. Geometries were meshed with tetrahedral linear elements, with material properties as follows: Elastic modulus of cortical bone equal to 16 GPa, elastic modulus of trabecular bone equal to 0.155 GPa, polyethylene equal to 1GPa and titanium equal to 110 GPa. The assumed Poisson's ratio was 0.3 in all except for polyethylene where we assumed a value of 0.4. The prosthesis was considered as glued to the adjacent bone. The finite element model was composed of 336 024 elements.

At the glenoid cavity, the major influence of the strain distributions was observed at the posterior-superior region, in both cortical and trabecular bone structures. The system presents critical region around holes of fixation in glenoid component. At the trabecular bone, the maximum principal strains at the posterior-superior region ranged from 2250 µε to 3000 µε. While at the cortical bone, the maximum principal strains were 300 µε to 400 µε.

The results observed evidence some critical regions of concern and the effect of implant in the bone strains mainly at the posterior-superior region of the glenoid cavity is pronounced. This indicates that this region is more affected by the implant if bone remodeling is a concern and it is due to the strain-shielding effect, which has been connected with loosening of the glenoid component.

Total knee replacements (TKR) have been the main choice of treatment for alleviating pain and restoring physical function in advanced degenerative osteoarthritis of the knee. Recently, there has been a rising interest in minimally invasive surgery TKR (MIS-TKR). However, accurate restoration of the knee axis presents a great challenge. Patient-specific-instrumented TKR (PSI-TKR) was thus developed to address the issue. However, the efficacy of this new approach has yet to be determined. The purpose of the current study was thus to measure and compare the 3D kinematics of the MIS-TKR and PSI-TKR in vivo during sit-to-stand using a 3D fluoroscopy technology.

Five patients each with MIS-TKR and PSI-TKR participated in the current study with informed written consent. Each subject performed quiet standing to define their own neutral positions and then sit-to-stand while under the surveillance of a bi-planar fluoroscopy system (ALLURA XPER FD, Philips). For the determination of the 3D TKR kinematics, the computer-aided design (CAD) model of the TKR for each subject was obtained from the manufacturer including femoral and tibial components and the plastic insert. At each image frame, the CAD model was registered to the fluoroscopy image via a validated 2D-to-3D registration method. The CAD model of each prosthesis component was embedded with a coordinate system with the origin at the mid-point of the femoral epicondyles, the z-axis directed to the right, the y-axis directed superiorly, and the x-axis directed anteriorly. From the accurately registered poses of the femoral and tibial components, the angles of the TKR were obtained following a z-x-y cardanic rotation sequence, corresponding to flexion/extension, adduction/abduction and internal/external rotation.

During sit-to-stand the patterns and magnitudes of the translations were similar between the MIS-TKR and PSI-TKR groups, with posterior translations ranging from 10–20 mm and proximal translations from 29–31mm. Differences in mediolateral translations existed between the groups but the magnitudes were too small to be clinically significant. For angular kinematics, both groups showed close-to-zero abduction/adduction, but the PSI-TKR group rotated externally from an internally rotated position (10° of internal rotation) to the neutral position, while the MIS-TKR group maintained at an externally rotated position of less than 5° during the movement.

During sit-to-stand both groups showed similar patterns and magnitudes in the translations but significant differences in the angular kinematics existed between the groups. While the MIS-TKR group maintained at an externally rotated position during the movement, the PSI-TKR group showed external rotations during knee extension, a pattern similar to the screw home mechanism in a normal knee, which may be related to more accurate restoration of the knee axis in the PSI-TKR group. A close-to-normal angular motion may be beneficial for maintaining a normal articular contact pattern, which is helpful for the endurance of the TKR. The current study was the first attempt to quantify the kinematic differences between PSI and non-PSI MIS. Further studies to include more subjects will be needed to confirm the current findings. More detailed analysis of the contact patterns is also needed.

Physical functioning in patients undergoing hip surgery is commonly assessed in three ways: patient-reported outcome measure (PROM), performance test, or clinician-administered measure. It is recommended that several types of measures are used concurrently to capture an extended picture of function. Patient fatigue and burden, time, resources and logistical constraints of clinic and research appointments mean that collecting multiple measures is seldom feasible, leading to focus on a limited number of measures, if not a single one. While there is evidence that performance-tests and PROMs do not fully correlate, correlations between PROMs, performance tests and clinician-administrated measures are yet to be evaluated. It is also not known if the associations between function and patient characteristics depend on how function is measured. The aim of our study was to use different measures to assess function in the same group of patients before their hip surgery to determine 1. how well PROMs, performance tests and clinician-administrated measures correlate with one another and 2. Whether these measures are associated with the same patient characteristics.

We conducted a cross-sectional analysis of the pre-operative information of 125 participants listed for hip replacement. The WOMAC function subscale, Harris Hip Score (HHS) and walk-, step- and balance-tests were assessed by questionnaire or during a clinic visit. Participant socio-demographics and medical characteristics were also collected. Correlations between functional measures were investigated with correlation coefficients (r). Regression models were used to test the association between the patient's characteristics and each of the three types of functional measures.

None of the correlations between the PROM, clinician-administrated measure and performance tests were very high (r<0.90). The highest correlations were found between the WOMAC-function and the HHS (r=0.7) or the Walk-test (r=0.6), and between the HHS and the walk-test(r=0.7). All the other performance-tests had low correlations with the other measures(r ranging between 0.3 and 0.5).

The associations between patient characteristics and functional scores varied by type of measure. Psychological status was associated with the WOMAC function (p-value<0.0001) but not with the other measures. Age was associated with the performance test measures (p-value ranging from ≤0.01 to <0.0001) but not with the WOMAC function. The clinician-administered (HHS) measure was not associated with age or psychological status.

When evaluating function prior to hip replacement clinicians and researchers should be aware that each assessment tool captures different aspects of function and that patient characteristics should be taken into account. Psychological status influences the perception of function; patients may be able to do more than they think they can do, and may need encouragement to overcome anxiety. A performance test like a walk-test would provide a more comprehensive assessment of function limitations than a step or balance test, although performance tests are influenced by age.

For the most precise description of functional status a combination of measures should be used. Clinicians should supplement their pre-surgery assessment of function with patient-reported measure to include the patient's perspective.

Anterior cruciate ligament deficiency (ACLD) affects the performance of walking in some patients (non-copers) while copers are able to minimize the effects via proper musculoskeletal compensations. Since many daily activities are more challenging than level walking, e.g., obstacle-crossing, it is not clear whether copers are able to cope with such a challenging task. A successful and safe obstacle-crossing requires not only sufficient foot clearance of the swing limb, but also the stability of the body provided mainly by the stance limb. Failure to meet these demands may lead to falls owing to loss of balance or tripping over obstacles. The purpose of the current study was to identify the motor deficits and/or biomechanical strategies in coper and non-coper ACLD patients when crossing obstacles of different heights for a better function assessment.

Ten coper and ten non-coper ACLD patients were recruited in the current study. The non-coper ACLD subjects were those who had not been able to return to their pre-injury level activities, had at least once giving way during the last six months and their Lysholm knee scale was less than 70 [1]. Each subject walked and crossed obstacles of heights of 10%, 20% and 30% of their leg lengths at a self-selected pace. Kinematic and kinetic data were measured with a 7-camera motion analysis system (Vicon, Oxford Metrics, U.K.) and two force plates (AMTI, U.S.A.). The leading and trailing toe clearances were calculated as the vertical distances between the toe markers and the obstacle when the toe was directly above the obstacle. Joint angles of both limbs, and joint moments of the stance limb, were calculated. Peak extensor moments at the knee during stance phase and the corresponding joint angles were extracted for statistical analysis. A 3 by 2, 2-way mixed-model analysis of variance with one between-subject factor (group) and one within-subject factor (obstacle height) was performed (α=0.05). SAS version 9.2 was used for all statistical analysis.

Compared with the copers, significantly reduced leading and trailing toe clearances were found in the non-coper group (P<0.05). The non-copers showed significantly decreased peak extensor moments (P<0.05) and flexion angle at the affected knee during the stance phase before leading limb crossing (P<0.05).

Distinctive gait patterns were identified in coper and non-coper patients with unilateral anterior cruciate ligament deficiency during obstacle crossing. During the stance phase before the un-affected leading limb crossing, the non-copers showed significantly reduced flexion and peak extensor moments at the affected knee (i.e., quadriceps avoidance), primarily owing to the impaired stability at the affected knee. The significantly reduced leading and trailing toe clearances in the non-coper group indicate that the non-coper ACLD patients are at a higher risk of tripping over the obstacle, and may have difficulty in regaining balance owing to the unstable ACLD knee. Advanced rehabilitation program or reconstruction of the ACL is suggested for the non-coper group.

The flat foot is a frequent deformity in children and results in various levels of functional alterations. A diagnosis based on foot morphology is not sufficient to define the therapeutic approach. In fact, the degree of severity of the deformity and the effects of treatments require careful functional assessment. In case of functional flatfoot, subtalar arthroereisis is the surgical treatment of choice. The aim of this study is to evaluate and compare the functional outcomes of two different bioabsorbable implants designed for subtalar arthroereisis in childhood severe flat foot by means of thorough gait analysis.

Ten children (11.3 ± 1.6 yrs, 19.7 ± 2.8 BMI) were operated for flat foot correction [1,2] in both feet, one with the calcaneo-stop method, i.e. a screw implanted into the calcaneus, the other with an endoprosthesis implanted into the sinus-tarsi. Gait analysis was performed pre- and 24 month post-operatively using a 8-camera motion system (Vicon, UK) and a surface EMG system (Cometa, Italy) to detect muscular activation of the main lower limb muscles. A combination of established protocols, for lower limb [3] and multi-segment foot [4] kinematic analysis, was used to calculate joint rotations and moments during three level walking trials for each patient. At the foot, the tibio-talar, Chopart, Lisfranc, 1^st metatarso-phalangeal joints were tracked in three-dimensions, together with the medial longitudinal arch.

Significant differences in standard X-ray measurements were observed between pre- and post-op, but not between the two treatment groups. Analysis of the kinematic variables revealed functional improvements after surgery. In particular, a reduction of eversion between the shank and calcaneus (about 15° on average) and a reduction of inversion between metatarsus and calcaneus (about 18° on average) were detected between pre- and post-operatively after both treatments. Activation of the main plantar/dorsiflexor muscles was similar at both pre- and post-op assessments with both implants.

The combined lower limb and multi-segment foot kinematic analyses were found adequate to provide accurate functional assessment of the feet and of the lower limbs. Both surgical treatments restored nearly normal kinematics of the foot and of the lower limb joints, associated also to a physiologic muscular activation.

In vitro biomechanical tests allow obtaining important information about stresses and deformations inside the bone, and about the displacements of the prosthetic device under physiological load conditions. This information may be helpful for the development of innovative devices, for the improvement of the existing ones, and for defining optimized procedure for bone reconstruction depending on the typology of bone defects.

The definition of a robust and reproducible reference frame is the first step in order to perform a consistent biomechanical test [1]. The aims of the current study was to define an anatomical reference frame for pelvis which can also be applied to a hemi-pelvis. A robust alignment method was sought so as to replicate the anatomical pose during in vitro applications. The intra- and inter- operator repeatability was quantified to corroborate the results.

The anatomical reference frame was derived from the anterior pelvic plane [2] and was adapted for in vitro applications. It was based on the following anatomical landmarks: Anterior Superior Iliac Spine (ASIS, defined as the most prominent point on the external iliac surface); Posterior Superior Iliac Spine (PSIS) defined as the upper and most prominent projection on the posterior border of the iliac wing); Pubic Tubercle (PT, defined as the most medial point on the extension of inner line of upper oval foramen).

The alignment procedure represented an improved version of a previous procedure [3]. The hemi-pelvis has been positioned on blocks of plasticine close to the landmarks on a 5-screws adjustable plate. Three steps were performed: position of the landmarks at the same height; alignment of the PSIS and PT on a horizontal line parallel to x- direction; position of the setup in front of a 6 degrees of freedom manipulator so that both the manipulator and the 5-screws adjustable plate are in the same reference frame. The manipulator was used to move the specimen in the following steps: clamping and lifting up of the specimen; rotation around x-axis in the posterior direction by 45°; rotation around y-axis in the medial direction by 90°; rotation around x-axis (antero-posterior direction) until PT and ASIS lay in the same vertical plane.

Five operators performed the alignment of a male and a female hemi-pelvis, three times each. The repeatability of the current procedure was good, with uncertainties below 1.0° within the same operator, and of less than ±1.5° between operators for the male hemipelvis, and ±2° for the female one. Thanks to the good results the reference frame and the alignment procedure may be adopted for in vitro biomechanical testing on hemi-pelvic specimen, for example to test acetabular bone reconstruction or acetabular prosthetic devices.

Posterolateral rotatory instability (PLRI) is the most common type of elbow instability. It is caused by an insufficiency of the lateral ligamentous complex, which consists mainly of the radial collateral ligament (RCL) and the lateral ulnar collateral ligament (LUCL).

Investigate the influence of serial sectioning of the lateral ligamentous complex on elbow stability in a cadaveric model of PLRI.

Kinematics of six fresh frozen cadaveric elbow specimens were measured by digitizing anatomical marks with a Microscribe 3DLX digitizing system (Revware Inc, Raleigh, NC). Each specimen was tested under four conditions: Intact, LUCL tear, LUCL and RCL tear, and complete Tear (LUCL, RCL and capsule tear). Each specimen was tested in 30°, 60° and 90° elbow flexion angles. Varus- laxity was measured in supination, pronation, and neutral forearm rotation positions and total forearm rotation was measured with 0.3 Nm of torque. Statistical significant differences between the conditions were detected using a two-way ANOVA with Tukey's post-hoc test.

The radial head dislocated in all specimens in LUCL and RCL tear and Comp but not in LUCL tear. Total forearm ROM did not increase form intact to LUCL tear (p>0.05) but significantly increased in LUCL and RCL tear (p=0.0002) and complete tear (p<0.0001) in all flexion angles. Additionally, ROM in LUCL tear significantly differed from LUCL and RCL tear and complete tear (p=0.0027 and p=0.0002). A similar trend was seen with the varus angle. While there was a significant difference when the intact condition was compared to both the LUCLand RCL tear and complete tear conditions (p<0.0001 and p<0.0001), there was no difference between the intact and LUCL tear conditions.

LUCL tear alone is not sufficient to cause instability and increase ROM and varus angle, meanwhile the increase of ROM and varus angle with additional capsular tear was not significant compared to LUCL and RCL tear. The increase of ROM after LUCL and RCL tear is an unknown symptom of PLRI.

The stem and the rasp for cemented arthroplasty are typically designed to obtain a cement mantle 2–5 mm thick. However, sometimes a line-to-line cementation is preferred, where the femoral cavity is prepared with the same dimension as the actual stem. There are contrasting reports [1,2] about the suitability of this technique to withstand the long-term fatigue loads. While the theoretical geometry allows no space for the cement, a sort of cement mantle is formed as the cement penetrates in the spongy bone. The scopes of this study were: 1) developing a dedicated in vitro method to test line-to-line cementation; 2) assessing if a short, polished hip stem designed for a standard cementation can be safely cemented line-to-line.

In order to perform long-term mechanical in vitro tests, composite bones must be used, as cadaveric bones cannot withstand millions of loading cycles [3]. For this study, the Sawbones Mod. 3406-4 were chosen: they feature an open-cell polyurethane core simulating low-density spongy bone. Post-implantation x-rays confirmed that a relevant cement-bone interdigitation was obtained. Four femurs were prepared with a CoreHip (Aesculap) with regular cement mantle (Regular). Another 4 femurs were rasped to the same rasp size, and implanted with line-to-line cementation with a larger stem (Line-to-line). The implanted femurs were subjected to an accelerated test derived from a validated protocol [3] which replicates the most demanding motor tasks of 24 years of patient activity. Implant elastic micromotions and permanent migrations were measured throughout the test. The implants were then sectioned and treated with dye penetrants to highlight the cement cracks.

Elastic and permanent motions did not show any loosening trend, and never exceeded few micrometers. As expected, some damage was visible in the cement mantles after test completion, for both types of implantation (similar to retrieved cement mantles surrounding stable implants [3]. The cement damage was similar in all specimens. No sign of major disruption was visible, neither within the Regular nor in the Line-to-line specimens: in fact, the cracks were limited in length, did not seem to cross the entire mantle thickness, and did not result in any loose cement fragments. The cracks in the line-to-line implants showed the same position and distribution compared to those found in the regular implants, but were slightly longer in some specimens.

This in vitro study confirmed the feasibility of simulating line-to-line cementation in vitro. Our results suggest that a stem designed for a regular cement mantle could induce slightly more damage when implanted line-to-line, but no significant trend toward loosening.

Identification of gait deviations and compensations in patients with total hip arthroplasty (THA) is important for the management of their fall risks. To prevent collapse of the lower limbs while balancing and supporting the body, proper combinations of joint moments are necessary. However, hip muscles affected by THA may compromise the sharing of load and thus the whole body balance. The current study aimed to quantify the control of body support in patients with THA in terms of the total support moment (Ms) and contributions of individual joint moments to Ms during walking.

Six patients who underwent unilateral THA via an anterolateral approach for at least six months at the time of the gait experiment, and six age- and gender-matched healthy controls were recruited. Twenty-eight infrared retro-reflected markers were placed on specific landmarks of the pelvis-leg apparatus to track the motion of the segments during walking. Kinematic and kinetic data were measured using an 8-camera motion analysis system (Vicon, Oxford Metrics, U.K.) and two force plates (AMTI, U.S.A.). The Ms of a limb was calculated as the sum of the net extensor moments at the hip, knee and ankle during stance phase. The contributions of the hip, knee and ankle to the first and second peaks of Ms (Ms1 and Ms2) were calculated by dividing the joint moment value by the corresponding peak values of Ms. Independent t-tests were performed to compare between groups at a significance level set at α=0.05 using SAS version 9.2 (SAS Institute Inc., NC, USA).

No significant differences in Ms1 and Ms2 were found between the THA group and normal controls (P >0.05). However, compared to the healthy controls, significantly increased hip and ankle contributions but decreased knee contributions to Ms1, and significantly increased hip contributions but decreased ankle contributions to Ms2 were found in the THA group.

Similar Ms1 and Ms2 between groups indicates that the lower limbs in the THA group were able to provide normal body supports. However, this was achieved via an altered contributions of the hip, knee and ankle. Hip and knee extensors play important roles in supporting the body when the Ms1 occurs during early stance of walking. In the THA group, greater hip and ankle contributions but lesser knee contributions for the Ms1 indicates that the function of hip extensors were not affected but compensatory mechanisms of the knee and ankle were found. For the Ms2, hip flexor and ankle plantarflexors are important for supporting the body during late stance. Decreased hip flexor (i.e., greater hip extensor contributions) and ankle plantarflexor moments in the THA patients suggests that the hip flexors and ankle plantarflexor muscles were affected by THA surgery. Hip muscles affected by the THA may compromise the sharing of load at the hip and thus the whole body balance. Further postoperative rehabilitation is suggested for the patients following THA. Further studies on the effects of different surgical approaches on the support moments is needed for improving treatment plans.

Subtalar arthrodesis known as talocalcaneal fusion is an end-stage treatment for adult hind foot pathologies. The goal of the arthrodesis is to restrict the relative motion between bones of the subtalar joints, aiming to reduce pain and improve function for the patient. However, the change of the subtalar structures through the fusion is considered a disturbance to the joint biomechanics, which have been suggested to affect the biomechanics of the adjacent joints. However, no quantitative data are available to document this phenomenon. The purpose of the current study was to quantify the effects of subtalar arthrodesis on the laxity and stiffness of the talocrural joint in vitro using a robot-based joint testing system (RJTS) during anterioposterior (A/P) drawer test.

Six fresh frozen ankle specimens were used in this study. The lateral tissues of the specimens were removed but the anterior and posterior talofibular ligaments and calcaneofibular ligament were kept intact. A/P drawer tests were performed on each of the specimens at neutral position, 5° and 10° of dorsiflexion, and 5?and 10?of plantarflexion using a robot-based joint testing system (RJTS), before and after subtalar arthrodesis. The RJTS enabled unconstrained A/P drawer testing at the prescribed ankle position while keeping the proximal/distal and lateral/medial forces, and varus/valgus and internal/external moments to be zero. This was achieved via a force-position hybrid control method with force and moment control, which has been shown to be more accurate than other existing force-position hybrid control methods. The target A/P force applied during the A/P drawer test was 100N in both anterior and posterior directions. The stiffness and laxity were calculated from the measured force and displacement data. The anterior and posterior stiffness of the talocrural joint were defined as the slope beyond 30% of the target A/P force, and the peak displacements quantified the laxity of the joint. Comparisons of laxity and stiffness between the intact and fusion ankle specimens were performed using Wilcoxon signed rank test (SPSS 19.0, IBM, USA) and a significance level of 0.05 was set.

Subtalar arthrodesis did not lead to significant changes in the stiffness and laxity in both anterior and posterior directions (P>0.05). The mean anterior stiffness before arthrodesis was 9.54±1.17 N/mm and was 10.35±2.40 N/mm after arthrodesis. The mean anterior displacements before and after arthrodesis were 9.68±0.94 mm and 8.97±1.42 mm, respectively.

Subtalar arthrodesis did not show significant effects on the A/P laxity and stiffness of the talocrural joint in both anterior and posterior directions. This may imply that the motion of the subtalar joints do not have significant effects on the A/P stability of the talocrural joint, which is the main joint of the ankle complex. This agrees with the anatomical roles of the subtalar joints which provide mainly the varus/valgus motions for the ankle complex. The current study provides a basis for further studies needed to evaluate the effects subtalar arthrodesis on the varus/valgus stability.

Posterior cruciate ligament deficiency (PCLD) leads to structural and proprioceptive impairments of the knee, affecting the performance of daily activities including obstacle-crossing. Therefore, identifying the biomechanical deficits and/or strategies during this motor task would be helpful for rehabilitative and clinical management of such patients. A safe and successful obstacle-crossing requires stability of the body and sufficient foot clearance of the swing limb. Patients with PCLD may face demands different from normal when negotiating obstacles of different heights. The objective of this study was thus to identify the biomechanical deviations/strategies of the lower limbs in unilateral PCLD during obstacle-crossing using motion analysis techniques.

Twelve patients with unilateral PCLD and twelve healthy controls participated in the current study with informed written consent. They were asked to walk and cross obstacles of heights of 10%, 20% and 30% of their leg lengths at self-selected speeds. The PCLD group was asked to cross the obstacles with each of the affected and unaffected limb as the leading limb, denoted as PCLD-A and PCLD-U, respectively. The kinematic and kinetic data were measured with a 7-camera motion analysis system (Vicon, Oxford Metrics, U.K.) and two force plates (AMTI, U.S.A.). The angles of the stance and swing limbs (crossing angles) and the moments of the stance limbs (crossing moments) for each joint in the sagittal plane when the leading limb was above the obstacle were calculated for statistical analysis. A 3 by 2, 2-way mixed-model analysis of variance with one between-subject factor (PCLD-A vs. Control, and PCLD-U vs. Control) and one within-subject factor (obstacle height) was performed (α=0.05). Paired t-test was used to compare the variables between PCLD-A and PCLD-U (α=0.05). SAS version 9.2 was used for all statistical analysis.

When the leading toe was above the obstacle, the PCLD group showed significantly greater hip flexion in the swing limb but decreased dorsiflexion in the stance limb, both in PCLD-A and PCLD-U (P<0.05). Greater knee flexion and greater ankle dorsiflexion were found in the leading limb in PCLD-A (P<0.05). Meanwhile, the PCLD group showed significantly decreased ankle plantarflexor but increased knee extensor crossing moments in the stance limb compared with the Control (P<0.05). None of the calculated variables were found to be significantly different between PCLD-A and PCLD-U (P>0.05).

When crossing the obstacle, patients with PCLD reduced ankle plantarflexor moments that were mainly produced by the gastrocnemius. This may help reduce the posterior instability of the affected knee. Greater knee extensor crossing moments may also help reduce the posterior instability of the standing knee when the leading toe was above the obstacle.

The changed joint kinetics as a result of PCLD were not only seen on the affected side but also on the unaffected side during obstacle-crossing. This symmetrical pattern may be necessary in performing functional activities that may require either the affected side or the unaffected side leading. These results suggest that rehabilitative intervention, including muscular strengthening, on both affected and unaffected sides are necessary in patients with unilateral PCLD.

Osteoarthritis of the first metatarsophalangeal (MTP1) joint is a common disorder in elderly, resulting in pain and disability. Arthrodesis of this joint shows satisfactory results, with relieve of pain in approximately 85% of the patients. However, the compensation mechanism for loss of motion in the MTP1 joint after MTP1 arthrodesis is unknown. A reduced compensation mechanism of the foot may explain the disappointing result of MTP1 arthrodesis in the remaining 15% of the patients. This study was conducted to elucidate this compensation mechanism. We hypothesize that the ankle and forefoot are responsible for compensation after MTP1 arthrodesis.

Gait was evaluated in eight patients with arthrodesis of the MTP1 joint (10 feet) and twelve healthy controls (21 feet) by using a sixteen-camera Vicon-system. The four-segmental, validated Oxford-Foot-Model was used to investigate differences in range of motion of the hindfoot-tibia, forefoot-hindfoot and hallux-forefoot segment during stance. For statistical analysis, the unpaired t-test with Bonferroni correction (p<0.0125) was performed.

No differences in spatiotemporal parameters were observed between both groups. In the frontal plane, MTP1 arthrodesis decreased the range of motion in midstance, while an increased range of motion was observed in terminal stance for the hindfoot relative to the tibia in the transversal plane. Subsequently range of motion in the forefoot in preswing was increased. This resulted in less eversion in the hindfoot during midstance, increased internal rotation of the hindfoot during terminal stance and more supination in the forefoot during preswing in the MTP1 arthrodesis group. Motion of the hallux was restricted in the loading response (i.e. plantar flexion) and terminal stance (i.e. dorsiflexion).

As hypothesized, both the ankle and the forefoot are responsible for compensation after MTP1 arthrodesis, because arthrodesis causes less eversion and increased internal rotation of the hindfoot and increased supination of the forefoot. As expected, both dorsiflexion and plantar flexion of the hallux was restricted due to arthrodesis. These findings suggest a gait pattern in which the lateral arch of the foot is more loaded and the stiff hallux is avoided during the stance phase of gait.

Our results indicate that proper motion of the forefoot and ankle joint is important when considering arthrodesis of the MTP1 joint. Therefore, we emphasize careful assessment the range of motion in the forefoot and ankle joint in the pre-operative situation, since patients with a decreased range of motion in the forefoot and ankle joint have a less functioning compensation mechanism. We currently perform a study to evaluate the strength of the positive correlation between the pre-operative range of motion in the forefoot and ankle joint and the clinical outcome.

Calcium phosphate cements (CPC) are used as biocompatible and bioactive bone void fillers. Ideally, the mechanical properties of these cements should match those of the surrounding bone. The knowledge of the real mechanical properties of the material is important in the decision-making process regarding possible use of the CPCs in different anatomical sites. Although it is generally recognized that these cements are stiffer and more brittle than desired, there is a limited amount of data about the possible deformation of this class of material before failure. The focus of this study was to determine these properties of injectable CPCs.

Two different types of self-setting CPCs were investigated in this study: i) hydroxyapatite (HA), that historically has been the most widely studied CPC; ii) brushite, that recently has attracted attention due to its faster resorption than that of HA in vivo. Specimens of both cement types were prepared by mixing a powder phase with a liquid phase that were left to harden in phosphate buffered saline at 37°C. Once set, the specimens underwent a quasi-static compressive test to determine the compressive strength, the elastic modulus and the maximum deformation of the two materials. The material testing machine was equipped with a digital image correlation system, which allows accurate measurement of material deformation directly on the specimen surface.

Brushite was found to be significantly more stiff (+80%) and resistant (+84%) than HA. Similar findings were found for the energy needed to create a first crack on the specimen surface. However, the first crack appeared on the specimen surface at the same low deformation level (∼0.15%) independently of the type of material tested. Complete failure of both materials occurred, on average, before reaching 0.25%.

It has been demonstrated that the compressive behaviour of CPCs depends on their composition and porosity [1]. One of the main reasons for the high strength and stiffness of the brushite studied here was its low porosity (∼12%). However, the maximum deformation is not positively affected by this decrease in porosity. In fact, both materials show the same brittle behaviour, i.e. they undergo comparably little deformation before they break. Under these conditions, increasing the compressive strength may not always be beneficial clinically, e.g. in the treatment of vertebral compression fractures, where the high stiffness of the bone cements used has been identified as a risk factor for adjacent-level fractures [2]. However, it is not clear whether a 20-fold higher stiffness than the trabecular bone would give a different clinical outcome than a 10-fold higher stiffness. These high-strength, high-stiffness cements may also be used as a basis for further biomaterial development, e.g. in the creation of macro-porous scaffolds, which is usually challenging due to the commonly low mechanical properties of the base CPC material.

For the treatment of irreparable meniscal injuries, we developed a novel multilayer meniscal scaffold, consisting of collagen, strontium and cellulose derived from Luffa Cylindirica; and we evaluated its effects on meniscal regeneration and arthritic changes in a rabbit partial meniscectomy model.

The meniscus has a key role in shock absorbtion, load distribution, chondroprotection and stability of the knee joint. Meniscal injuries are one of the most common orthopedic injuries and may lead to degenerative cartilage changes and eventually osteoarthritis. Repair of the meniscal tissue is the treatment of choice for patients with a meniscus lesion, however, this is not always possible, especially for degenerative tears or injuries located on the inner avascular zone. To overcome the devastating outcomes of meniscectomy for such injuries, several materials have been developed and tried to replace the resected meniscal tissue. These scaffolds were designed primarily to relieve pain after meniscectomy, and later on were aimed to prevent osteoarthritis and cartilage damage that may develop in the future. In the quest for optimum scaffold material small intestine, tendons and other isolated tissues, collagen and polyurethane have been researched. Nevertheless, none of these materials have absolutely proven satisfying identical replacement of resected meniscal tissue. Therefore, we developed and investigated a novel multilayer meniscal scaffold, consisting of collagen, strontium and cellulose derived from Luffa Cylindirica (a cucumber shaped and sized plant, known as sponge gourd). The aim of the study was to evaluate the meniscal regeneration and arthritic changes after partial meniscectomy and application of novel multilayer meniscal scaffold in a rabbit model and to compare the results with clinically used polyurethane scaffold (Actifit, Orteq Ltd, London, UK)

Sixteen male, mature, NewZealand rabbits weighing between 2600–3500 g were randomly divided into three groups. All groups underwent knee surgery via a medial parapatellar approach and a reproducible 1.5-mm cylindrical defect was created in the avascular zone of the anterior horn of the medial meniscus bilaterally. Defects were filled with the polyurethane scaffold in Group 1 and novel multilayer scaffold was applied to fill the defects in Group 2(n:6). Four rabbits in Group 3 did not receive any treatment and defects were left empty. Animals were sacrified after 8 weeks and bilateral knee joints were taken for macroscopic, biomechanical, and histological analysis.

No signs of inflammation or infection were observed in all animals. Macroscopic evaluation of tibial plateaus after excision of menisci was performed with digital images of inked condylar surfaces. No significant degenerative changes were detected between groups. Digital photographs of excised menisci were also obtained and surface areas were measured by a computer software (Image J version 1.46, National Institute of Health, Bethesda, MD). There was a slightly larger meniscus area in the first two groups than the no treatment group, however, this was not found significant. Indentation testing of the tibial condyle and compression tests for the relevant meniscal areas with a diameter of 3mm was also performed in all groups. Histological analysis was made and all specimens were stained with safranin O and scored according to a scoring system.

In this study, the initial evaluation of novel multilayer meniscal scaffold demonstrated promising biomechanical and histological results; besides no adverse events related to scaffold material was observed.

Worldwide 500,000 cases of maxillofacial cancer are diagnosed each year. After surgery, the reconstruction of large bone defect is often required. The induced membrane approach (Masquelet, 2000) is one of the strategies, but exhibits limitations in an oncological context (use of autografts with or without autologous cells and Bone Morphogenetic Proteins). The objectives of this work are to develop an injectable osteoinductive and osteoconductive composite matrix composed of doped strontium (Sr) hydroxyapatite (HA) particles dispersed within a polysaccharide scaffold, to evaluate in vitro their ability to stimulate osteoblastic differentiation of human mesenchymal stem cells (hMSC) and to stimulate in vivo bone tissue regeneration.

HA particles were synthesized with different ratios of Sr. X-ray diffraction (XRD), Inductively Coupled Plasma (ICP), and particle size analysis (Nanosizer™) were used to characterize these particles. HA and Sr-doped HA were dispersed at different ratios within a pullulan-dextran based matrices (Autissier, 2010), Electronic scanning microscopy Back Scattering Electron microscopy (ESEM-BSE) and ICP were used to characterize the composite scaffolds. In vitro assays were performed using hMSC (cell viability using Live/Dead assay, expression of osteoblastic markers by quantitative Polymerase Chain Reaction). Matrices containing these different particles were implanted subcutaneously in mice and analyzed by Micro-Computed Tomography (micro-CT) and histologically (Masson's trichrome staining) after 2 and 4 weeks of implantation.

XRD analysis was compatible with a carbonated hydroxyapatite and patterns of Sr-doped HA are consistent of Sr substitution on HA particles. Morphological evaluation (TEM and Nanosizer™) showed that HA and Sr-doped HA particles form agglomerates (150 nm to 4 µm). Matrices composed with different ratios of HA or Sr-doped-HA, exhibit a homogenous distribution of the particles (ESEM-BSE), whatever the conditions of substitution. In vitro studies revealed that Sr-doped HA particles within the matrix stimulates the expression of osteoblastic markers, compared to non-doped HA matrices. Subcutaneous implantation of the matrices demonstrated the formation of a mineralized tissue. Quantitative analyses show that the mineralization of the implants is dependent of the amount of HA particles dispersed, with an optimal ratio of 5% of particles. Histological analysis revealed osteoid tissue in contact to the matrix.

In conclusion, the ability of this injectable composite scaffold to promote ectopically tissue mineralization is promising for bone tissue engineering. Osseous implantation in a femoral bone defect in rats is now in progress. 5% of doped HA particles were implanted within the induced membranes in a context of radiotherapy procedure. Micro-CT analyses are ongoing. This new matrix could represent an alternative to the autografts for the regeneration of large bone defects in an oncological context.

Hydrogels as scaffolds provide a suitable environment for the cells (biocompatibility, biodegradability). Their biomechanical properties are very important to provide not only direct support to the surrounding tissue but also provide a local microenvironment. There is an interest in composite hydrogels with hydroxylapatite or bioactive glass (BAG) for tuning of their bioactivity and biomechanical properties [1].

Hydrogels were prepared from a polysaccharide gellan gum (GG), dissolved in ultrapure water at 90°C under constant stirring to a final concentration of 2 wt.% GG. Sodium-free BAG (70 wt.% SiO₂, 30 wt.% CaO) was synthesized using a sol-gel technique with particles of ∼100 nm, clustered to ∼10 µm large agglomerates [1]. The hydrogel composites were prepared by admixing up to 2–8 wt.% of BAG powder into a solution of GG during sonication, and pouring the hot BAG-GG suspension with following cooling to room temperature. Mechanical properties were evaluated using different protocols in creep (0.1 to 1.2 N), strain sweep (1 to 20 µm) and frequency scan (100 to 0.1 Hz) modes, with specimens immersed in water at 25°C.

Maximum load (or deformation) before breaking of scaffold materials is a very important material property but is rarely measured. Here creep experiments at different applied stresses were carried out first. These loads exert more proper stress on the scaffold material that results in deformation, which is not the same as during deformation in relaxation or stress-strain tests [2]. The second set of experiments was made at physiologically relevant conditions (1 Hz frequency and small amplitude-controlled deformation) [3].

Amount of 2% BAG was found to be sufficient to get nearly linear deformation in the whole measured strains region, but at higher concentration stress deviated from linearity at strains exceeding ∼0.5% at 1 Hz. Storage modulus (E') did not significantly change and the loss tangent was found nearly constant (∼0.1) for the whole frequency range, indicating a strong network structure of BAG-doped hydrogel. Additions of 2% BAG give a ten-fold increase in both storage and loss moduli, whereas further increase of BAG content does not show further stiffening. The application of tailored protocols [3] allowed analysis of dynamic, creep and relaxation tests in the same device with same specimens, which might be not possible for other techniques.

Creep data would provide valuable information in addition to dynamic modes to predict long-term behaviour of the composite hydrogels. Properly tailored protocols could mimic, for example, articular cartilage or other tissue working conditions and allow evaluation of the side effects like swelling at early stage, which measurements are usually rather cumbersome.

In the area of 3D printing, more and more maxillofacial surgery departments are equipped with 3D printers to build their own anatomical models or surgical guides. Prior to be printable, the patients' DICOM imaging data has to be converted to a 3D virtual model, a 3D mesh. The file format most commonly used is the STL (Standard Tesselation Language) file format. Many programs exist that are able to convert DICOM data to STL files. Commercial software, such as Surgicase CMF© are FDA- and CE-approved whereas free programs, available online do not have the approval. However, the latter are often used anyway because of financial reasons. In this article, we investigate whether 6 of these software solutions are equivalent or not.

Thin slice CT imaging data of a patient's mandible (in DICOM file format) was converted to STL meshes with 6 different software solutions. One commercial program, Surgicase CMF©, was used to build the reference model. Then 5 free programs were used to create 5 models of the same mandible, specifying the same thresholding parameters: InVesalius 3.0, 3DimViewer 2.2.4, 3D Slicer, itk-Snap and Seg3D. All of these models were loaded in Netfabb Basic 6.4 to retrieve dimensional data, geometric information and the number of holes in each mesh. Finally, the models were then compared to the reference model using CloudCompare 2.6.2.

All models created with free software differed from the reference model in the 3 dimensions. Mean length difference was −0.74 mm [−2.06; −0.32] (SD: 0.74), mean width difference −0.45 mm [−0.76; −0.25] (SD: 0.19) and mean height difference was 0.41 mm [0.14; 0.62] (SD: 0.18). Although the height was increased in all models, both the length and width were systematically decreased, resulting in an average decrease of volume of −7.1 cm³ [−7.45; −6.77] (SD: 0.32). The number of triangles used to create each mesh ranged from 20944 to 368244, resulting in a variation of the file size from 1023 Ko to 80462 Ko (0.16 to 12.70 times the file size of the reference model). Two of the free programs created meshes with errors, such as the presence of holes (non-watertight meshes) that could be repaired with Netfabb.

Free programs able to convert volume imaging data to a printable virtual mesh do not provide equivalent results. Variations were noted in the three plane of space with a systematic difference between free programs and the commercial FDA-approved one. While the length and width were less than a millimeter different to the reference, the dimension that most varied was the length with a difference reaching −2.06 mm with itk-Snap. Geometric data also varied significantly, the number of triangles composing the meshes being much different than the reference, resulting in variable file sizes. This traduces the fact that algorithms used by the programs are not the same. In the era of 3D printing made directly accessible in surgical departments, great attention should be paid to the accuracy of the models created with free software.

Reconstructing mandibular and maxillary bone defects with free vascularized bone flaps requires to take into account the aesthetic and functional requirements to consider subsequent placement of dental implants. It implies a three-dimensional conformation of the bone fragment. This is usually done by making osteotomies on the bone harvested. The aim of our study was to evaluate the interest of virtual planning and 3D printing using free software and a consumer printer in this indication.

Invesalius® software (Technology of Information Renato Archer Center, Campinas, Brazil) was used to build virtual models from the patients' CT scan imaging data. The surgical procedure was planned using Meshmixer® (Autodesk, San Rafael, United States). Meshlab® software (Visual Computing Lab, Pisa, Italy) was used to design cutting guides for the flap harvest and modelling. 3D printing of these guides with a consumer printer (Ultimaker 2® Ultimaker B.V., Geldermalsen, the Netherlands) allowed the transfer of the planning to the operating room.

Three patients requiring mandibular reconstruction underwent an iliac crest free flap, a fibula free flap and a scapula free flap, and could benefit from this technique. In each case, the bone resection was performed virtually and the positioning of the bone available at the donor site was simulated on screen. This allowed to anticipate the position and orientation of the cutting planes on the bone flap. From the anatomy of the donor site and the cutting planes, harvest templates and cutting guides could be designed by computer. Planning the conformation of the bone flap to the recipient site has allowed an anatomical, aesthetic and functional reconstruction of the bone defect.

Surgeon-made virtual planning and “low cost” 3D printing helps harvest the bone flap and position and orient the osteotomies to adapt it to the defect. They provide, both the patient and the surgeon, reduced operative time and better anticipation of the result, particularly in the context of the maxillofacial reconstruction. Compared to commercially available custom-made devices, this technique allows the manufacture of the guides without delay and at a cheap price.

The management of maxillofacial injuries requires restoring the contours of the facial skeleton to achieve an aesthetic outcome. When fractures are simple, open reduction and rigid fixation with stock titanium osteosynthesis plates is usually sufficient. However, when the damage is more substantial (when the fracture is comminuted or in case of a bone defect) anatomical landmarks are lost and the reconstruction requires the use of titanium meshes. These meshes are usually modelled intraoperatively to restore the contours of the bone. This can be a tough and time consuming task in case of minimal invasive approach and intraoperative edema. When the injury is unilateral, printing a 3D anatomical model of the mirrored unaffected side is an easy way to accurately pre-bend the mesh preoperatively. With the emergence of “low cost” consumer 3D printers, the aim of our study was to evaluate the cost of this technique in a department of maxillofacial surgery.

The first part of the study was to evaluate free software solutions available online to determine which of these could be used to create 3D virtual models from the patients' volume imaging data, mirror the model and export an STL file suitable for 3D-printing with a consumer 3D-printer. The second part was to identify the desktop 3D-printers commercially available according to the different technology used, their prices and that of consumables required.

Five free software solutions were identified to create STL meshes of the patient's anatomy from thin slice CT scan DICOM data. Two more were available to repair, segment and mirror them to provide a clean STL file suitable for 3D printing with a desktop 3D printer. The prices of 2 different printers were then listed for each of the 3 additive manufacturing technologies available to date. Prices ranged from 2,299 € for the Ultimaker 2+© (Fuse Deposition Modeling, FDM), to 4,999 € for the Sintratec© printer (Selective Laser Sintering, SLS), the Formlabs 2© (stereolithography) being at an intermediate price of 3,299 €. Finally, the cost of the manufacture of a model was calculated for each of these printers. Considering a model of a supraorbital ridge printed to restore the anterior wall of the frontal sinus, the volume of the mesh is around 20 cm³. This represents a cost of less than 1 € with the FDM technology, 4.70 € with stereolithography and 1.50 € with the SLS printer.

Since patents of additive manufacturing have become part of the public domain, the cost of 3D printing technology has fallen drastically. Desktop printers are now an investment accessible to a surgery department and the cost of the material is low. This allows the surgeons, by the mean of free software, to directly create 3D models of their patients' anatomy, mirror them if needed and manufacture a template to pre-bend titanium meshes that will be subsequently sterilized for the surgery. Having the printer in the department reduces manufacturing lead times and makes this technique possible even for urgent cases.

The surface of any implant device plays an important role in their biocompatibility. After implantation, the physico-chemical surface properties of any biomaterial determine its good/bad response against protein adsorption, cell attachment and proliferation and bacterial adhesion [1]. In this sense, the knowledge of hydrophobicity and surface tension of any new-developed biomaterial is an added value for the final product. Polymeric implants, among which are poly-D-Lactic acid (PLDA), are well characterized biodegradable biomaterials that have been proposed as an alternative to metallic implants for fracture fixation. However, their use in the clinical practice has been limited due to insufficient osseointegration and adverse tissue reactions. Recently it has been demonstrated the feasibility of introducing Mg particles within the PLDA matrix as a new strategy to improve the bioactivity and mechanical properties of PLDA whereas simultaneously modulating the degradation rate of Mg [2]. In this work, the surface of new amorphous and crystalline composites of PLDA with two different Mg concentrations are characterized in terms of hydrophobicity and surface tension.

Amorphous and crystalline PLDA from Natureworks were reinforced with Mg particles through a processing route that contained four different stages: drying, hot extrusion, grinding and compression moulding. Two different Mg concentration were used: 1 wt.% and 10 wt.% Hydrophobicity was obtained by goniometry using water as probe liquid (θ_W). The surface tension was determined through the Young Equation using water, formamide and diiodomethane as probe liquids. Van Oss approach was used to split the surface tension into the Lifshitz-van der Waals component (γ^LW) and acid-base component (γ^AB). The acid-base was also divided into the electron-donor (γ⁻) and electron-acceptor parameters (γ⁺).

The water contact angle was similar in amorphous and crystalline samples. Mg always reduced the θ_W value, no matter the Mg concentration used. Reductions were similar for both Mg concentrations. The surface tension in amorphous samples was comprised between 26 and 36 mJ/m² and in crystalline samples was between 30 and 36 mJ/m². Although values were very similar, the deviations observed for crystalline samples were always smaller than for amorphous. An important effect of Mg in the composites was the increase in the parameter γ-.

Mg addition makes the polymer less hydrophobic. The increase of γ⁻ may be related to an increase in the negative surface charge of Mg samples. The hydrophobic reduction plus the more negative surface could impair the bacterial approach and further adhesion to the surface of the new composites, which implies an advance in the fight against infections.

Medical grade polyurethanes have been widely promoted for biomedical applications. In particular, the use of polycarbonate-urethanes (PCU) has drawn considerable attention in the orthopaedic device industry as a result of their excellent mechanical properties, biostability and biocompatibility. PCUs have been extensively utilized in vascular grafts, stents and artificial heart valves. Specifically, bionate thermoplastic PCU, commercially produced by DSM PTG (Berkeley, California), has been of great interest in the field of orthopaedics because of its outstanding load-bearing properties and excellent wear resistance. Also, it is characterized by its long-term durability and resistance to hydrolytic degradation making it a good candidate for in-vivo orthopaedic applications. PCUs have been considered for meniscal replacement because of its unique weight-bearing capabilities, ability to withstand intense forces within the knee joint and ease of lubrication due to its hydrophilic nature. In addition, the low frictional properties essential for a meniscal replacement is obtainable with PCUs.

Materials used for this study were a commercial polycarbonate-urethanes, Bionate PCU 80A (B8) and 90A (B9) pellets, and polyethylene continuous strands fibres (PE) obtained from DSM Polymer Technology Group, USA. Some quantity of the B8 and B9 pellets were dried separately in a vacuum oven at 100°C for 14 hours. A custom mould was designed for the production of the mechanical test samples. The quantity of the constituent materials was determined using composite theory known as the Rule of Mixtures.

$E_c=E_m{V}_m+E_f{E}_f$

where V_m and V_f are the volume fraction of the matrix and fibre respectively. Three specimens each of the prepared composites were tested for tensile and compression strength and at a crosshead speed of 12 mm/min using a Zwick/Roell 1484 Material Testing Machine.

The PCUs were not as stiff as their fibre-reinforced composites, which indicate that the stiffness of the PCU composite materials is a function of both the stiffness of the PCU matrix and the interspersed fibres. The tensile moduli of composites of B8 and B9 increased appreciably with PE. An increase of 227% was obtained for the B8 with the incorporation of PE fibres while percentage increase in stiffness for B9 was 148% for PE reinforcement fibres. The compressive modulus dropped with the inclusion of the PE fibres in the B9, a reduction of 55% was recorded while an increment of 4% was obtained with PE added to the B8.

The results from this study demonstrate that the tensile and compressive properties of PCU can be custom-tailored to that of the meniscal tissue by systematically embedding reinforcement fibres into the PCU matrix such that a composite with desirable mechanical properties is obtained. The results of both tensile and compressive results visibly revealed the reinforcing effect of the fibres used in this study. However, additional studies are required to completely describe the PCU composite as a candidate meniscal substitute capable of gaining its full functionality.

Current strategy for orthopedic tissue engineering mainly focusses on the regeneration of the damaged tissue using cell-seeded three-dimensional scaffolds. Biocompatible scaffolds with controllable degradation and suitable mechanical property are required to support new tissue in-growth and regeneration ^[1]. Porous composite scaffolds made from organic and inorganic materials are highly preferred, which can mimic the natural bone in their composition as well can enhance tissue repair ^[2]. Scaffolds with optimum mechanical strength in both dry and wet state are more suitable for in vivo orthopedic application. Biphasic calcium phosphate (BCP), a biocompatible ceramic and carboxymethyl cellulose (CMC), a semi-natural polymer are used in the study to prepare composite scaffolds. Citric acid is used as a crosslinking agent for the polymer to improve its stability ^[3]. Stability, mechanical property in dry and wet conditions and cytocompatibility of the scaffolds were investigated.

Cellulose-BCP (BC25) and crosslinked cellulose-BCP (BC25CA) scaffolds are fabricated by freeze-drying method. The stability of the scaffolds was assessed in phosphate buffered saline (PBS) and compressive modulus was measured in dry and wet condition. Cytocompatibility was assessed by culturing pre-osteoblast cells at a density of 2.5×10⁴ on crosslinked scaffold and cell proliferation was measured by performing MTT assay on day 4 and 7.

Crosslinked scaffold was more stable than non-crosslinked scaffold in aqueous environment as the latter disintegrated within few hours in the solution. Non-crosslinked scaffold showed higher compressive modulus of 116.3±14.8 kPa in dry condition but is reduced to 1.2±0.7 kPa in hydrated state. Though the crosslinked scaffold shows low compressive modulus of 37.67±6.7 kPa in dry state, it exhibited appreciable compressive moduli of 17.15±1.3 kPa in hydrated state. Thus, the crosslinking of the scaffolds improved the stability as well as the mechanical strength in wet condition. Cytocompatibility was assessed by culturing pre-osteoblast cells and from the MTT assay, it is shown that the cells are proliferating on the crosslinked scaffolds with time which indicates that the scaffolds are non-toxic and cytocompatible. Stability and optimum mechanical property for scaffold in aqueous environment are highly crucial for in vivo hard tissue regeneration.

This study demonstrated the preparation of crosslinked scaffolds which exhibited good stability and mechanical strength in wet condition along with a porous architecture, controlled degradability and cytocompatibility, hence, crosslinked cellulose-BCP scaffold can be used for orthopedic application.

Bone loss continues to be a clinical and therapeutic problem. Bone reconstruction of osseous defects is a challenge after fracture and traumatic injuries, infections and tumors. The common objective is to regenerate bone morphology and function. Several techniques have been developed to promote bone formation, but the advent of new biomaterials allows us to take an entirely different approach to the treatment of bone voids. However, the use of bone substitutes should be considered carefully, as not all biomaterials behave the same way in humans. Calcium phosphate ceramics are osteoconductive materials that promote bone regeneration. The aim of this study was to retrospectively evaluate the clinical, radiographic and histological results of bone loss treated with an adjunct injectable biphasic bone substitute (BBS).

We analysed the results of patients with fractures and a bone defect that were treated using an injectable BBS (calcium sulfate + hydroxyapatite) and those that were treated using the same bone substitute with antibiotic (gentamicin and/or vancomycin). Patient outcome was evaluated clinically and radiographically. In 9 cases samples for histological analysis were obtained.

From July 2009 to May 2015, 126 cases (cs) on 111 patients (pt) (calcaneus: 53 cs, 47 pt; tibia: 32 cs, 30 pt; Femur: 14 cs, 9 pt, Elbow: 5 cs, 5 pz; humerus 2 cs, 2 pz; wrist 7cs, 7pz; forearm 6 cs, 4 pz; foot 2 cs, 2 pz; Phalanx 5 cs, 5 pt) were treated at our hospital with a BBS. The mean follow-up was 15 months, and bone ingrowth was assessed at 1, 2, 3, 6 and 12 months by X-ray. In all cases, the calcium sulphate phase of the BBS dissolved within 4–6 weeks, and new bone formation was observed at 6 months. On six patients large bone was treated with a revision surgery (autologous cancellous bone graft combined with BBS and antibiotic). No complications were reported.

The 9 histological samples confirmed gradual remodeling and regeneration of the bone substitute over time.

This biomaterial is versatile, offers a good augment for hardware and bone alignment, is biocompatible and osteoconductive, and has allowed us to manage significant bone voids. Histological analysis of samples from the tibia, ulna and calcaneus have confirmed the ability of this bone substitute to remodel into bone.

Polyethylene wear of joint replacements can cause severe clinical complications, including; osteolysis, implant loosening, inflammation and pain. Wear simulator testing is often used to assess new designs, but it is expensive and time consuming. It is possible to predict the volume of polyethylene implant wear from finite element models using a modification of Archard's classic wear law [1–2]. Typically, linear elastic isotropic, or elasto-plastic material models are used to represent the polyethylene. The purpose of this study was to investigate whether use of a viscoelastic material model would significantly alter the predicted volumetric wear of a mobile-bearing unicompartmental knee replacement.

Tensile creep-recovery experiments were performed to characterise the creep and relaxation behaviour of the polyethylene (moulded GUR 4150 samples machined to 180×20×1 mm). Samples were loaded to 3 MPa stress in 4 minutes, and then held for 6 hours, the tensile stress was removed and samples were left to relax for 6 hours. The mechanical test data was used fit to a validated three–dimensional fractional Maxwell viscoelastic constitutive material model [3]. An explicit finite element model of a mobile–bearing unicompartmental knee replacement was created, which has been described previously [4]. The medial knee replacement was loaded to 1200 N over a period of 0.2 s. The bearing was meshed using quadratic tetrahedral elements (1.5 mm seeding size based on results of a mesh convergence study), and the femoral component was represented as an analytical rigid body. Wear predictions were made from the contact stress and sliding distance using Archard's law, as has been described in the literature [1–2]. A wear factor of 5.24×10⁻¹¹ was used based upon the work by Netter et al. [2]. All models were created and solved using ABAQUS finite element software (version 6.14, Simulia, Dassault Systemes).

The fractional viscoelastic material model predicted almost twice as much wear (0.119 mm³/million cycles) compared to the elasto-plastic model (0.069 mm³/million cycles). The higher wear prediction was due to both an increased sliding distance and higher contact pressures in the viscoelastic model.

These preliminary findings indicate the simplified elasto-plastic polyethylene material representation can underestimate wear predictions from numerical simulations. Polyethylene is known to be a viscoelastic material which undergoes creep clinically, and it is not surprising that it is necessary to represent that viscoelastic behaviour to accurately predict implant wear. However, it does increase the complexity and run time of such computational studies, which may be prohibitive.

Using Python scripting it is possible to automate the pre-processing, solving and post-processing stages of finite element analysis using ABAQUS software. This is particularly useful when running multiple models parametrically. When the model involves a bony part, it is necessary to assign material properties based on the CT scan to represent bone heterogeneity, and unfortunately this cannot currently be done from within ABAQUS using software such as Bonemat [1]. To address this issue a Python package was written called ‘py_bonemat_abaqus’ to assign material properties from within ABAQUS. The purpose of this study was to compare the material assignments of py_bonemat_abaqus and Bonemat, to compare the processing speed, and to describe the workflow.

The software packages were compared using a CT scan of a half pelvis downloaded from the VAKHUM database, and the associated hexahedral finite element mesh of the left half pelvis. To examine different element types, the hexahedral mesh was converted to linear and quadratic tetrahedral elements by dividing each hexahedron into 5 tetrahedral elements. The equations used to convert the Hounsfield Unit (HU) values to apparent density (p_app), and to convert the apparent density to elastic modulus (E) are shown in Equations 1&2 [2].

Equation 1: p_app = −0.021075 + 0.000786 HU

Equation 2 E = 2.0173 p_app^2.46

The time taken to analyse the models by each software was assessed using a Windows 7 PC with a 64-bit operating system, 4 CPUS, 8 GB of RAM and an Intel Core I5-3470 processor.

The mean difference between the moduulus assignment made by py_bonemat_abaqus and Bonemat was −0.05 kPa (range −10.19 to 4.50 kPa, standard deviation 0.62 kPa). The Python package took a similar time to run for all element types; this was between 109 and 126 s. Bonemat software was significantly faster, and took between 5 and 20 s. Finally, the Python package was successfully used from within a Python script to perform material assignment from within ABAQUS software in a fully automated manner.

Material assignments were almost equivalent between the two software packages, with any differences explainable by rounding effects. To put the differences into context, a difference of −0.05 kPa is 0.00000002% of the typical modulus of cortical bone (20.7 GPa), and 0.00000003% of the modulus of trabecular bone (14.8 GPa) [3]. The Python package was slower to process the models, but was successfully able to assign material properties from within ABAQUS software as part of an automated script.

In clinical orthopedics suitable materials that induce and restore biological functions together with the right mechanical properties are particularly needed for the regeneration of musculoskeletal tissue. An innovative solution to answer this need is represented by tissue engineering. This technique could overcome the limits of traditional approaches involving the use of homologous, autologous or allogenetic tissue (e.g. tissue availability, immune rejection and pathogen transfer). In this field, rapid prototyping techniques are emerging as the most promising tool to realize three-dimensional tissue constructs with highly complex geometries.

Based on CAD/CAM technology, rapid prototyping allows development of patient-specific 3D scaffolds from digital data obtained with latest generation imaging tools. These structures can be realized in different materials, tailoring their mechanical properties and architectural features. Most rapid prototyping techniques allow the creation of acellular 3D scaffolds, which must be subsequently seeded with cells. Conversely, 3D bioprinting can deposit bio-ink containing molecules/cells, providing desired spatial distribution of growth factors/cells within the scaffold. The need of printable materials suitable for processing with inkjet, dispensing, or laser-print technologies, forces the use of matrices within a specific range of viscosity. However, these materials have low mechanical features. To overcome this problem and to obtain a final construct with good mechanical properties, bioprinting tissue fabrication can rely on the alternate deposition of thermoplastic materials and cell-laden hydrogels. Since mechanical performance is determined not only by the material properties but also by the geometry (microarchitecture) of the structure, printing parameters can be modified to obtain the desired features.

The new 3D platform available at Rizzoli Orthopaedic Institute, consisting of a Computer Tomography (GE Medical Systems, Milano, Italia) and a 3D Bio-Printer (RegenHU, Villaz-St-Pierre, Switzerland) is used to address the above-mentioned issues. Preliminary results showed that it is possible to modify the microarchitecture of the printed structures adjusting their apparent density and stiffness in the range of the trabecular bone tissue. Additionally, it has been proven that the calcium phosphate based paste, used as bioink, allows cell attachment and proliferation. Therefore, the platform allows to print scaffolds with open and interconnected porosities and suitable mechanical properties. They can be filled with different components such as cells or soluble growth factors at specific locations.

The Temporomandibular joint (TMJ) is a complex and important joint for daily activities, and the alloplastic implant is recommended as the best solution, after repeated surgeries, failed autogenous grafts, highly inflammatory metabolic arthritis, fibrous or bony ankyloses. Some complications in total TMJ replacement are associated with implant design, screw fixation failure, implant displacement, fibrous tissue formation, (Speculand, et al. 2000). Some numeric studies evaluate the number of screws needed to guarantee the good fixation and suggest a minimum of three (Ramos et al. 2015), but is a controversy conclusion. The Biomet Microfixation TMJ stock prosthesis, Jacksonville, FL, USA is one of the three or four in the market. Clinical studies published by this device between 2005 and 2015 indicate a success rate of around 84 to 91% with improvements in mouth opening, a decrease in pain score and improved quality of life. The present study analyses experimentally the load transfer of this device.

The intact, clean cadaveric ramus was instrumented with four rosettes model (KFG-1-120-D17-11 L3M2S, by Kywoa Electronic Instruments Co™, Japan), one in lateral region, two in lateral region and one in lingual face. The condyle was loaded with the temporal reaction; the load was applied constant velocity of 1mm/min in three continuum phases and with three stops at 100N, 200N and 300N. Next, the Biomet microfixation implant was fixed to the same cadaveric mandibular ramus after resection. The implant was 50mm in length. It was fixed with five 6AL/4V Titanium self-tapping screws with 2.7mm diameter were long enough to establish a bi-cortical support. The screws were screwed into the bone with a torque-screwdriver a constant torque of 0.2Nm. The same rosettes were analyzed before and after implantation and the mandible displacement two.

The experimental results for the mandibular ramus present a linear behavior up to 300N load in condyle, with the Biomet implant influencing strain distribution; the maximum influence was near the implant (rosette #4) is around 59%. The average vertical displacement of the mandibular ramus (300N) was measured by machine: 1.18 (±0.02) mm for the intact mandibular ramus and 1.21 (±0.02) mm for the implanted one, which represents a 2.8% differences between the experimental models and reduce of stiffness. The maximum principal strain deformation was observed in the rosette #3 with 1360µε more 20% than the intact mandible for 300N of reaction.

The experimental results show that the Biomet TMJ mandibular ramus implant changes the load transfer in the ramus, compared to the intact, with its strain shielding effect. The results indicate the minimum number of screws is three to guarantee a good load transfer but the surface preparation of condyle presents an important factor.

Highly cross-linked polyethylene (HXLPE) is now a common used bearing surface in total hip arthroplasty. Current studies report superior wear rates with the use of HXLPE in total hip arthroplasty. However, there are few studies to support its long term use. The aim of this study is to measure the long term wear of HXLPE and evaluate patient satisfaction at more than 10 years follow up.

44 total hip arthroplasties were performed through a direct lateral approach by a single surgeon. All patients received the same uncemented acetabular component, mean liner thickness was 6.91mm (SD= 0.68). 16 of the femur components were cemented. Outcomes analysed include wear rates, osteolysis, revision rates, SF12 and Oxford hip scores. Wear rate was calculated using computer software (Polyware®) using edge detection software.

Mean age at surgery was 58.9 years (SD= 11.67). The mean follow up was 11.3 years (SD= 1.19). There was no evidence of osteolysis and none had undergone revision surgery. Mean two dimensional wear was 0.38mm (SD= 0.25) and mean wear rate per year was 0.03mm (SD= 0.02, range 0.009 to 0.078). Oxford hip score at last follow up indicated satisfactory joint function (mean= 42 SD= 6.2).

Our results support the use of highly cross-linked polyethylene in primary total hip replacements. The absence of osteolysis and need for revision surgery over a mean of 11.3 years is very encouraging.

There is a critical need for safe innovation in total joint replacements to address the demands of an ageing yet increasingly active population. The development of robust implant designs requires consideration of uncertainties including patient related factors such as bone morphology but also activity related loads and the variability in the surgical procedure itself. Here we present an integrated framework considering these sources of variability and its application to assess the performance of the femoral component of a total hip replacement (THR).

The framework offers four key features. To consider variability in bone properties, an automated workflow for establishing statistical shape and intensity models (SSIM) was developed. Here, the inherent relationship between shape and bone density is captured and new meshes of the target bone structures are generated with specific morphology and density distributions. The second key feature is a virtual implantation capability including implant positioning, and bone resection. Implant positioning is performed using automatically identified bone features and flexibly defined rules reflecting surgical variability. Bone resection is performed according to manufacturer guidelines. Virtual implantation then occurs through Boolean operations to remove bone elements contained within the implant's volume. The third feature is the automatic application of loads at muscle attachment points or on the joint contact surfaces defined on the SSIM. The magnitude and orientation of the forces are derived from models of similar morphology for a range of activities from a database of musculoskeletal (MS) loads. The connection to this MS loading model allows the intricate link between morphology and muscle forces to be captured. Importantly, this model of the internal forces provides access to the spectrum of loading conditions across a patient population rather than just typical or average values. The final feature is an environment that allows finite element simulations to be run to assess the mechanics of the bone-implant construct and extract results for e.g. bone strains, interface mechanics and implant stresses. Results are automatically processed and mapped in an anatomically consistent manner and can be further exploited to establish surrogate models for efficient subsequent design optimization. To demonstrate the capability of the framework, it has been applied to the femoral component of a THR.

An SSIM was created from 102 segmented femurs capturing the heterogeneous bone density distributions. Cementless femoral stems were positioned such that for the optimal implantation the proximal shaft axis of the femurs coincided with the distal stem axis and the position of the native femoral head centre was restored. Here, the resection did not affect the greater trochanter and the implantations were clinically acceptable for 10000 virtual implantations performed to simulate variability in patient morphology and surgical variation. The MS database was established from musculoskeletal analyses run for a cohort of 17 THR subjects obtaining over 100,000 individual samples of 3D muscle and joint forces. An initial analysis of the mechanical performance in 7 bone-implant constructs showed levels of bone strains and implant stresses in general agreement with the literature.

UKA with mobile bearing is a one of the treatment of medial osteoarthritis. However, some reports refer to the risk of dislocation of the mobile bearing. Past reports pointed out that medial gap might be enlarged in deep flexion position (over 120 degrees), and says that it will lead to instability of the mobile bearing. The purpose of this study is to research the risk factors of enlargement of medial gap in deep flexion position.

We performed 81 UKAs with mobile bearing system from November 2013 to December 2015, and could evaluate 41 knees. This study of 41 knees included 9 males and 32 females, with average operation age of 75.4years(63–89years). The diagnosis was osteoarthritis in 39 knees and osteonecrosis in 2 knees. The UKA(Oxford partial knee microplasty, Biomet, Warsaw, IN) was used in all cases. We performed distal femur and proximal tibia osteotomy using CT-Free navigation system(Stryker Navigation System II/precision Knee Navigation ver4.0). And we inserted femoral and tibial trial component, then we placed an UKA tensioner on the medial component of the knee. Using tensioner under 30 lbs, we measured joint medial gap at 0,20,45,90,130(deep flexion) degrees. When we compared medial gap at 90 degrees position with at 130 degrees, we defined it as ‘instability group’ if there was gap enlargement more than 1mm, and defined it as ‘stability group’ if there wasn't.

We compared this two groups with regard to age, BMI, femoro-tibial angle (FTA), the diameter of anterior cruciate ligament (ACL), tibial angle and tibial posterior slope angle of the implant. We evaluated preoperative and postoperative FTA by weightbearing long leg antero-posterior alignment view X-rays. We measured ACL diameter at its condyle level in coronal view of MRI. Also we evaluated tibial component implantation angle by postoperative CT using 3D template system. These measurement were analyzed statistically using t test.

The stability group contained 26 knees, and the instability group contained 15 knees. Compared with the stability group, the instability group indicated higher FTA (p=0.001). Between 20 and 90 degrees flexion position, there was no change of medial gap.

Dislocation of the mobile bearing is one of the complications of UKA and it will need re-operation. It is said to be caused by impingement of the bearing and osteophyte of femur. However, some reports said that dislocation was happened when the knee was flexed deeply or twisted, and there was no impingement. We think it may means that dislocation could be caused by medial gap enlargement.

This study indicates that higher FTA could be risk factor of dislocation of mobile bearing. It is important to evaluate preoperatively FTA by X-ray.

Although cemented fixation provides excellent results in primary total hip replacement (THR), particularly in patients older than 75 years, uncemented implants are most commonly used nowadays. We compare the rate of complications, clinical and radiological results of three different designs over 75-years-old patients.

433 hips implanted in patients over 75 years old were identified from our Local Joint Registry. Group A consisted of 139 tapered cemented hips, group B of 140 tapered grit-blasted uncemented hips and group C of 154 tapered porous-coated uncemented hips. A 28 mm femoral head size on polyethylene was used in all cases. The mean age was greater in group A and the physical activity level according to Devane was lower in this group (p<0.001 for both variables). Primary osteoarthritis was the most frequent diagnoses in all groups. The radiological acetabular shape was similar according to Dorr, however, an osteopenic-cylindrical femur was most frequently observed in group A (p<0.001). The pre- and post-operative clinical results were evaluated according to the Merle-D'Aubigne and Postel scale. Radiological cup position was assessed, including hip rotation centre distance according to Ranawat and cup anteversion according to Widmer. We also evaluated the lever arm and height of the greater trochanter distances and the stem position. Kaplan-Meier analysis was done for revision for any cause and loosening.

The hip rotation centre distance was greater and the height of the greater trochanter was lower in group B (p=0.003, p<0.001, respectively). The lever arm distance was lower in group C (p<0.001). A varus stem position was more frequently observed in group B (p<0.001). There were no intra- or post-operative fractures in group A, although there were five intra-operative fractures in the other groups plus two post-operative fractures in group B and four in group C. The rate of dislocation was similar among groups and was the most frequent cause for revision surgery (8 hips for the whole series). The mean post-operative clinical score improved in all groups. The overall survival rate for revision for any cause at 120 months was 88.4% (95% CI 78.8–98), being 97.8% (95% CI 95.2–100) for group A, 81.8% (95% CI 64.8–98.8) for group B and 95.3% (95% CI 91.1–99.6) for group C (log Rank: 0.416). Five hips were revised for loosening. The overall survival rate for loosening at 120 months was 91.9% (95% CI 81.7–100), being 99.2%(95% CI 97.6–100) for group A, 85.5 (95% CI 69.9 −100) for group B and 100% for group C (Log Rank 0.093).

Despite a more osteopenic bone in the cemented group, the rate of peri-prosthetic fractures was higher after uncemented THR in patients older than 75 years. Although the overall outcome is good with both types of fixation, the post-operative reconstruction of the hip, which might be more reliable after cemented fixation, may affect the rate of complications in this population.

Total hip replacement (THR) in young patients has been associated to higher revision rates than in older population. Different conditions may lead to end-stage arthritis of the hip in these patients. We compared the clinical and radiological outcome of two different groups of young and very young patients who underwent a ceramic-on-ceramic THR.

120 hips were prospectively followed for a mean of 10.4 years (range, 5 to 17). 38 patients (46 hips) were less than 30 years old (group 1), and, 68 (74 hips) were between 31 and 40 years old (group 2). Weight (p<0.001) and physical activity level were greater in group 2 (p<0.001). Preoperative function (p=0.03) and range of mobility (p=0.03) were worse in group 1. Primary osteoarthritis was not found in any case. Rheumatoid juvenile arthritis was the most frequent diagnosis in group 1 and avascular necrosis of the femoral head in group 2. A femoral funnel-shaped type 1 according to Dorr was more frequent in group 2 (p=0.04). The same ceramic-on-ceramic uncemented THR was used in all cases. Screws for cup fixation were only used when strictly needed. We analysed the clinical results according to the Merle-D´Aubignè and Postel scale, the postoperative radiological reconstruction of the hip and the radiological appearance of cup loosening. Kaplan-Meier survivorship analysis was used to estimate the cumulative probability of not having a revision surgery.

Screw use required to obtain a secured interference fit of the acetabular component was found more frequently in group 1 (p=0.01). Postoperative pain (p=0.002) and function (p=0.002) were better in group 1. Mean acetabular abduction angle of the cup was greater in group 1 (p=0.03) and reconstruction to the hip rotation center according to Ranawat (p=0.01) was better in group 2. Placement of the acetabular component inside the Lewinnek´s zone and stem position were similar in both groups. No hips were revised due to complications related to ceramic or to stem loosening. Three cups were revised for aseptic loosening in group 1 and four in group 2. The survival rate for cup aseptic loosening at 15 years was 92.3% (95% CI: 83.7 to 100) for group 1 and 93.1% (95% CI: 85.3 to 99.9) for group 2 (Log rank, p=0.88).

Ceramic-on-ceramic uncemented THR is an excellent option for young and very young patients. Despite worse preoperative conditions in patients under the age of 30 years, a similar clinical outcome was found in this series.

A large number of total hip arthroplasties (THA) are performed each year, of which 60 % use cementless femoral fixation. This means that the implant is press-fitted in the bone by hammer blows. The initial fixation is one of the most important factors for a long lasting fixation [Gheduzzi 2007]. It is not easy to obtain the point of optimal initial fixation, because excessively press-fitting the implant by the hammer blows can cause peak stresses resulting in femoral fracture. In order to reduce these peak stresses during reaming, IMT Integral Medizintechnik (Luzern, Switzerland) designed the Woodpecker, a pneumatic reaming device using a vibrating tool. This study explores the feasibility of using this Woodpecker for implant insertion and detection of optimal fixation by analyzing the vibrational response of the implant and Woodpecker. The press-fit of the implant is quantified by measuring the strain in the cortical bone surrounding the implant. An in vitro study is presented.

Two replica femur models (Sawbones Europe AB, Malmo Sweden) were used in this study. One of the femur models was instrumented with three rectangular strain gauge rosettes (Micro-Measurements, Raleigh, USA). The rosettes were placed medially, posteriorly and anteriorly on the proximal femur. Five paired implant insertions were performed on both bone models, alternating between standard hammer blow insertions and using the Woodpecker. The vibrational response was measured during the insertion process, at the implant and Woodpecker side using two shock accelerometers (PCB Piezotronics, Depew, NY, USA). The endpoint of insertion was defined as the point when the static strain stopped increasing.

Significant trends were observed in the bandpower feature that was calculated from the vibrational spectrum at the implant side during the Woodpecker insertion. The bandpower is defined as the percentage power of the spectrum in the band 0–1000 Hz. Peak stress values calculated from the strain measurement during the insertion showed to be significantly (p < 0.05) lower at two locations using the Woodpecker compared to the hammer blows at the same level of static strain. However, the final static strain at the endpoint of insertion was approximately a factor two lower using the Woodpecker compared to the hammer.

A decreasing trend was observed in the bandpower feature, followed by a stagnation. This point of stagnation was correlated with the stagnation of the periprosthetic stress in the bone measured by the strain gages. The behavior of this bandpower feature shows the possibility of using vibrational measurements during insertion to assess the endpoint of insertion. However it needs to be taken into account that it was not possible to reach the same level of static strain using the Woodpecker as with the hammer insertion. This could mean that either extra hammer blows or a more powerful pneumatic device could be needed for proper implant insertion.

Knee arthroplasty with a rotating hinge knee (RHK) prosthesis has become an important clinical treatment option for knee revisions and primary patients with severe varus or valgus deformities and instable ligaments. The rotational axle constraints the anterior-posterior shear and varus-valgus moments, but currently used polyethylene bushings may fail in the mid-term due to insufficient creep and wear resistance of the material. Due to that carbon-fibre-reinforced (CFR) PEEK as an alternativ bushing material with enhanced creep, wear and fatigue behaviour has been introduced in a RHK design [Grupp 2011, Giurea 2014]. The objective of our study was to compare results from the pre-clinical biotribological characterisation to ex vivo findings on a series of retrieved implants.

In vitro wear simulation according to ISO 14243-1 was performed on rotating hinge knee devices (EnduRo® Aesculap, Germany) made out of cobalt-chromium and of a ZrN multi-layer ceramic coating for 5 million cycles. The mobile gliding surfaces were made out of polyethylene (GUR 1020, β-irradiated 30 ± 2 kGy). For the bushings of the rotational and flexion axles and the flanges a new bearing material based on CFR-PEEK with 30% PAN fiber content was used.

Analysis of 12 retrieved EnduRo^® RHK systems in cobalt-chromium and ZrN multi-layer in regard to

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loosening torques in comparison with initial fastening torques

with a focus on the four CFR-PEEK components integrated in the EnduRo^® RHK design.

For the rotating hinge knee design with flexion bushing and flanges out of CFR-PEEK the volumetric wear rates were 2.3 ± 0.48 mm³/million cycles (cobalt-chromium) and 0.21 ± 0.02 mm³/million cycles (ZrN multi-layer), a 10.9-fold reduction (p = 0.0016). The UHMWPE and CFR-PEEK particles were comparable in size and morphology and predominantly in submicron size [5]. The biological response to representative sub-micron sized CFR-PEEK particles has been demonstrated in vivo based on the leucoyte-endothelian-cell interactions in the synovia of a murine intra-articular knee model by Utzschneider 2010. Schwiesau 2013 extracted the frequency of daily activities in hip and knee replacement patients from literature and estimated an average of 1.76 million gait cycles per year. Thus, the 5 million cycles of in vitro wear testing reflect a mean in vivo service life of 2.9 years, which fits to the time in vivo of 12–60 months of the retrieved RHK devices. The in vitro surface articulation pattern of the wear simulation tests are comparable to findings on retrieved CFR-PEEK components for both types of articulations – cobalt-chromium and ZrN multi-layer coating.

For the rotating hinge knee design the findings on retrieved implants demonstrate the high suitability of CFR-PEEK as a biomaterial for highly loaded bearings, such as RHK bushings and flanges in articulation to cobalt-chromium and to a ZrN multi-layer coating.

GIRFT was published in the United Kingdom with the aim of streamlining primary care pathways, secondary care, creating a network of hospitals and treatment centres and to better regulate introduction of new implants. It also proposed the use of Orthopaedic Devices Evaluation Panel (ODEP) 10A* rated cemented implants in hip arthroplasty.

Aim: The purpose of this study was to assess the effects of adopting GIRFT on surgical time, length of stay, changes to the implants used and number of cases per surgical list.

Prior to adopting GIRFT, elective primary total hip replacement (THR) was predominantly uncemented THR. Age, sex, Body Mass Index (BMI), American Society of Anesthetiss (ASA), closure technique and surgical time of 50 consecutive primary uncemented THR were analysed to identify the appropriate statistical methods. Mean and standard deviation for surgical time were identified. Threshold increase in surgical time was set at 20 minutes. Based on expected difference of 20 minutes and standardised difference, minimum sample size was calculated to be 19. Prospective data on 60 consecutive uncemented THR and 30 consecutive cemented primary THR were included in this study. Inclusion criteria – primary THR for arthritis by single surgeon. Exclusion criteria – previous hip surgery, complex primary, abnormal anatomy.

No differences in age, sex, BMI, ASA and length of stay between the two groups. Surgical time was significantly increased by 28 minutes (p<0.001). Implants used changed from 7A*/5A* uncemented THR to 10A* (18/30) and 7A*(12/30) cemented THR. There was a reduction in number of THR done per surgical list due to the increase in surgical time (3 instead of 4).

GIRFT compliance improved from 0% cemented to 100% cemented. 0% 10A* rated implants to 66% 10A* rated implants. Undertaking cemented THR instead of uncemented THR is associated with significantly increased surgical time. Hence, number of THR surgeries performed in a day's list is accordingly reduced. There is potential for financial loss when the savings in the implants used is compared with the reduction in the number of surgeries performed.

Contrary to NICE guidance there remains a role for Austin-Moore hemiarthroplasty (AM) for patients with significant pre-existing comorbidities who are at higher risk of death and complications following cemented hemiarthroplasty.

We analysed prospectively-collected data comparing uncemented AM hemiarthroplasty in frail, poorly-mobile patients, and cemented hemiarthroplasty. We analysed age, pre-operative morbidity, duration of operation, death rate and complication rate.

AM patients were significantly older with significantly higher ASA grades. It took significantly longer to optimise them before surgery. AM was significantly shorter to perform. There was no significant difference in complications requiring re-operation. Twice as many AM patients developed post-operative pneumonia despite absence of cement. Twice as many AM patients died after surgery and a significant proportion died within the first month despite no increased risk of repeat operation, shorter operating time and no risk of cement-disease. We infer that these patients would likely have fared badly had they undergone a longer, cemented procedure. A modern cemented prosthesis costs £691 more than AM.

There exists a subset of patients within the neck of femur cohort who are significantly more unwell. Contrary to guidelines, we suggest that the cheaper, user-friendly Austin-Moore can be a reasonable prosthesis to use for this cohort.

At our district general hospital in the southwest of England, around 694 total knee replacements (TKR) are performed annually. Since spring 2013 we have been using an enhanced recovery protocol for all TKR patients, yet we have neither assessed compliance with the protocol nor whether its implementation has made a discernible and measurable difference to the delivery of care in this patient population. Enhanced recovery after surgery (ERAS) protocols are multi-modal care pathways designed to aid recovery. They are based on best evidence and promote a multi-disciplinary approach which standardises care and encompasses nutrition, analgesia and early mobilisation throughout the pre, intra and postoperative phases of an inpatient stay. ERAS has been found to reduce length of stay (LOS), readmission rates and analgesic requirements following surgery.^{1, 2, 3} Additionally, they have been shown to improve range of knee movement following TKR and improve mobility, patient satisfaction whilst reducing mortality and morbidity.^{4, 5, 6} With these benefits in mind, we sought to investigate how well our trauma and orthopaedic department was complying with a local ERAS protocol and whether we could replicate the benefits seen within the literature.

Following approval from our local audit office in September 2015 we generated a patient list of elective TKR patients under the same surgeon before and after the implementation of the ERAS protocol. Using discharge summaries and patient notes we extracted data for 39 patients operated on prior to the ERAS implementation between January 2011 and December 2012 and 27 patients following its introduction between January 2014 and September 2015. Data collected included length of stay, time to discharge from inpatient physiotherapy and use of analgesia and antiemetics. Alongside this we audited the compliance with all facets of the local ERAS protocol.

There was no statistically significant difference between the 2 groups in terms of demographics or pre-operative morbidity. Overall compliance with the ERAS protocol was good but there was some variability, especially with intraoperative medication and type of anaesthesia which was likely due to individual patient factors. Compliance with postoperative analgesia was especially good with 93% of patients receiving all 4 suggested analgesics within the ERAS group. Length of stay (LOS) was significantly reduced by 0.5 days per patient (p value < 0.4).

Overall compliance with the ERAS protocol was good but there was some variability, especially with intraoperative medication and type of anaesthesia, which was likely due to individual patient factors. Compliance with postoperative analgesia was especially good with 93% of patients receiving all suggested analgesics within the ERAS group. In terms of LOS, we found a statistically significant difference between the pre-ERAS and ERAS group of 0.5 days per patient. Within the context of our DGH, a 0.5 day reduction in LOS translates to around 350 bed days per year and a potential saving of GBP 105,000 (EUR 132,000) making this a clinically significant finding.

During revision THR, the surgery is often difficult and compromised due to lack of patient's bone especially in the pelvis. Any extra bone in the acetabulum is expected to be of advantage to the patient and the surgeon. The aim of this study was to see if preservation of medial acetabular osteophyte in uncemented total hip replacement had any adverse effect on the prosthesis survival or patient satisfaction.

Conventional acetabular preparation involves reaming down to the true floor. This not only medialises the centre of rotation of the hip but also reduces the acetabular offset. In contrast the main surgeon preserved the acetabular offset by preserving some osteophytic bone between the true floor of the acetabulum and the acetabular cup. This is achieved by reaming the acetabular cavity conservatively while achieving secure primary fixation of the prosthesis. We report the outcome of a single surgeon series of such cases. The endpoint was assessed as the need for revision of the acetabular cup.

A total of 106 consecutive patients were identified who underwent uncemented THR from 2005 to 2010. The medial osteophyte was measured on immediate post-operative x-rays, from the “teardrop” to the nearest point of the acetabular cup, by 3 surgeons (one consultant and 2 registrars). The patients were contacted for a telephone interview and their clinical notes, including x-rays, were reviewed.

Outcome was available for 79 patients. 74 patients were available for follow-up and 5 patients died unrelated to THR. Average follow-up was for 8.3 years (range 5.5–10.8). Average age was 62 years. The average medial osteophyte was 1.98 mm (range 0–14mm). One patient had late infection and one had dislocation. There was not a single failure of the acetabular component. The patient satisfaction was high at 8.8 out of 10.

Preservation of medial osteophyte in the acetabulum whilst doing uncemented THR has the advantage of retaining the patient's own bone stock which can be of great advantage to the surgeon as well as the patient should revision THR be required in future. Our study has shown that this can be achieved without compromising the survival of the prosthesis or the patient satisfaction.

This technique may increase the range of motion of the hip by reducing the risk of bony or soft tissue impingement, and also reduce the risk of dislocation. Furthermore, not recreating the native centre of rotation of the hip does not seem to have any adverse effect for the patients, who are very happy with the outcome. We recommend that whilst doing uncemented THR, the acetabulum should not be reamed to the true floor as has been the conventional teaching, but attempt should be made to preserve some medial osteophyte where possible, at the same ensuring that good primary fixation of the cup is achieved. This is to give the patient and surgeon the advantage of extra available bone should revision surgery be required in the future.

Positioning of the hip resurfacing is crucial for its long term survival and is critical in young patients for some reasons; manly increase the wear in the components and change the load distribution. THR have increased in the last years, mainly in young patients between 45 to 59 years old. The resurfacing solution is indicated for young patients with good bone quality. A long term solution is required for these patients to prevent hip revision. The resurfacing prosthesis Birmingham Hip Resurfacing (BHR) was analyzed in the present study by in vitro experimental studies. This gives indications for surgeons when placing the acetabular cup.

One synthetic left model of composite femur (Sawbones®, model 3403), which replicates the cadaveric femur, and four composite pelvic bones (Sawbones®, model 3405), were used to fix the commercial models of Hip resurfacing (Birmingham model). The resurfacing size was chosen according to the head size of femurs with 48 mm head diameter and a cup with 58 mm. They were introduced by an experimented surgeon with instrumental of prosthesis. The cup is a press fit system and the hip component was cemented using bone cement Simplex, Stryker Corp. The acetabular cup was analyzed in 4 orientations; in anteverion with 15º and 20°; and in inclination 40 and 45°. Combinations of these were also considered

The experimental set-up was applied according to a system previously established by Ramos et al. (2013) in the anatomic position. The femur rotates distally and the Pelvic moves vertically as model changes, such that the same boundary conditions are satisfied. This system allows compensating motions of the acetabular cup orientation. A vertical load of 1700 N was applied on all cases, which have resulted in joint reaction force of 2.4 kN. The femur and iliac bone was instrumented with rosettes. 5 repetitions at each position were conducted.

When the femur was instrumented with three rosettes in medial, anterior and posterior aspect, the maximum strain magnitude was observed in the medial aspect of femur with a minimum principal strain of −2070µε for 45° inclination and 20° of anterversion. The pubic region was found most critical region after instrumenting the Iliac bone with four rosettes, with a minimum principal strain around −2500µε (rosette 1), for the 45° inclination and 20° of anterversion. We have observed the great influence of the inclination on the strain distribution, changing its magnitude from compression to traction in different bone regions.

The minimum principal strain is more critical in medial aspect of the femur and the influence of strain is about 7% when orientation and inclination change. The maximum influence was observed in the anterior aspect, where the anteversion presents a significant influence. The results show the interaction between inclination and anterversion in all aspects, being observed lower values in lower angles.

The orientation of the acetabular cup significantly influences the strain distribution on the iliac surface. Besides, as anterversion increases, more strains are induced, mainly in the region of iliac body (rosette 3).

The mechanical alignment (MA) for Total Knee Arthroplasty (TKA) with neutral alignment goal has had good overall long-term outcomes. In spite of improvements in implant designs and surgical tools aiming for better accuracy and reproducibility of surgical technique, functional outcomes of MA TKA have remained insufficient. Therefore, alternative, more anatomical options restoring part (adjusted MA (aMA) and adjusted kinematic alignment (aKA) techniques) or the entire constitutional frontal deformity (unicompartment knee arthroplasty (UKA) and kinematic alignment (KA) techniques) have been developed, with promising results. The kinematic alignment for TKA is a new and attractive surgical technique enabling a patient specific treatment. The growing evidence of the kinematic alignment mid-term effectiveness, safety and potential short falls are discussed in this paper. The current review describes the rationale and the evidence behind different surgical options for knee replacement, including current concepts in alignment in TKA. We also introduce two new classification systems for “implant alignments options” and “osteoarthritic knees” that would help surgeons to select the best surgical option for each patient. This would also be valuable for comparison between techniques in future research.

Ceramic-on-ceramic (CoC) total hip arthroplasty (THA) can produce articular noise during the normal activities, generating discomfort to the patient. THA noise has to be investigated also as a potential predictor and a clinical sign of prosthetic failure.

An observational study has been carried out to characterize the noise in CoC cementless THA, and to analyze the related factors. A total of 46 patients with noisy hip have been enrolled in 38 months, within the follow-up protocol normally applied for the early diagnosis of ceramic liner fracture [1]. Noise recording was based on a high-quality audible recorder (mod. LS 3, Olympus, Japan) and a portable ultrasonic transducer (mod USB AE 1ch, PAC, USA). The sensors for noise recording were applied to the hip of the patient during a sequence of repeatable motorial activities (forward and backward walking, squat, sit in a chair, flexion and extension of the leg). Sessions were also video-recorded to associate the noise emission to the specific movements.

Each noise event was initially identified by the operator and therefore classified by comparison to the spectral characteristics (duration, intensity and frequency) of the main noise types. Number and spectral characteristics of noise events were obtained and correlated to the factors describing the clinical status of the patient, the surgical approach, the prosthetic device implanted. The study investigated also the noise as a sign of implant failure, by comparison with the total number of implants failed in the cohort during the study.

We observed three types of noise with the main spectral characteristics in agreement to the literature: clicking, squeaking and popping. Among the identified types of noise, squeaking showed the longest duration and the highest amplitude. The 63% of hip presented the emission of just one type of noise, while the remaining a mix of types. The movement with the highest presence of noise was walking, followed by squat. Correlation was found between the noise type and the dimension of the ceramic head (p<0.001), with the sizes of 32 mm more affected by squeaking that the smaller one. Squeaking appeared before during the follow-up than the other types of noise. The 35% (16/46) of the noisy hips were revised during the study. Among the revised hips, the 81% (13/16) were affected by impingement and/or severe damage of the prosthetic components. The antiversion of the cup (p=0.008), the presence of debris in the synovial fluid (p=0.021) and the average frequency of squeaking (p=0.006) were significant predictors for the revision, but it has to be mentioned that the squeaking data was obtained on a small subset of revised patients. Ultrasonic analysis did not show significant correlations.

The study presented and validated an experimental procedure to analyze noisy hips in clinical trials. Noise is confirmed to be a significant parameter in the follow-up evaluation of ceramic THA.

Analysis of the morphology of the distal femur, and by extension of the femoral components in total knee arthroplasty (TKA), has largely been related to the aspect ratio, which represents the width of the femur. Little is known about variations in trapezoidicity (i.e. whether the femur is more rectangular or more trapezoidal). This study aimed to quantify additional morphological characteristics of the distal femur and identify anatomical features associated with higher risks of over- or under-sizing of components in TKA.

We analysed the shape of 114 arthritic knees at the time of primary TKA using the pre- operative CT scans. The aspect ratio and trapezoidicity ratio were quantified, and the post- operative prosthetic overhang was calculated. We compared the morphological characteristics with those of 12 TKA models.

There was significant variation in both the aspect ratio and trapezoidicity ratio between individuals. Femoral trapezoidicity was mostly due to an inward curve of the medial cortex. Overhang was correlated with the aspect ratio (with a greater chance of overhang in narrow femurs), trapezoidicity ratio (with a greater chance in trapezoidal femurs), and the tibio- femoral angle (with a greater chance in valgus knees).

This study shows that rectangular/trapezoidal variability of the distal femur cannot be ignored. Most of the femoral components which were tested appeared to be excessively rectangular when compared with the bony contours of the distal femur. These findings suggest that the design of TKA should be more concerned with matching the trapezoidal/ rectangular shape of the native femur.

The most common reasons for total joint arthroplasty (TJA) failure are aseptic loosening (AL) and prosthetic joint infection (PJI). There is a big clinical challenge to identify the patients with high risk of AL/PJI before the TJA surgery. Although there is evidence that genetic factors contribute to the individual susceptibility to AL/PJI, a predictive model for identification of patients with a high genetic risk of TJA failure has not been developed yet.

We aimed to develop a risk evaluation tool utilising the AL/PJI-associated polymorphisms for identification of patients with high genetic risk of TJA failure based on inflammation-gene polymorphism panel.

Based on allele and genotype frequencies of twenty-five single nucleotide polymorphisms (SNPs) in TNF, IL2, IL6, IL10, IL1b, IL-1Ra, MBL2, MMP1, FTO genes and those influencing the serum levels of biomarkers of TJA outcomes (IL6, CCL2/MCP-1, CRP, ESR) in peripheral blood obtained from patients with TJA (AL, n=110; PJI, n=93; no complications, n=123), we calculated a hazard ratio and a relative entropy of alleles and genotypes associated with AL and PJI and their combinations in patient subgroups.

We conducted a risk evaluation tool based on the presence of risk alleles and genotypes in TNF (rs361525, rs1800629), DARC (rs12075), MBL2 (rs11003125) and FTO (rs9939609, rs9930506) genes associated with implant failure (AL/PJI). Of these, FTO gene variations (rs9939609, rs9930506) were associated mainly with PJI (P=0.001, OR=2.04, 95%CI=1.132–2.603; P=0.011, OR=1.72, 95%CI=1.338–3.096) and DARC (rs12075) with AL (P=0.005, OR=1.79, 95%CI=1.193–2.696). This tool calculates a hazard ratio of a combination of SNPs associated with AL and PJI for identification of patients with high and low risk of AL/PJI TJA failure.

We proposed a risk evaluation tool for stratification of patients before the TJA surgery based on the genetic risk of AL/PJI development. The effect size for each genotype combination described in the study is small. Further multiparametric data analysis and studies on an extended patient cohort and other non-genetic and genetic parameters are ongoing. Grant support: AZV MZ CR VES16-131852A, VES15-27726A, IGA LF UP_2016_011.

Systemic metal ion monitoring (Co;Cr) has proven to be a useful screening tool for implant performance to detect failure at an early stage in metal-on-metal hip arthroplasty. Several clinical studies have reported elevated metal ion levels after total knee arthroplasty (TKA), with fairly high levels associated with rotating hinge knees (RHK) and megaprostheses¹. In a knee simulator study, Kretzer², demonstrated volumetric wear and corrosion of metallic surfaces. However, prospective in vivo data are scarce, resulting in a lack of knowledge of how levels evolve over time. The goal of this study was to measure serum Co and Cr levels in several types TKA patients prospectively, evaluate the evolution in time and investigate whether elevated levels could be used as an indicator for implant failure.

The study was conducted at Ghent University hospital. 130 patients undergoing knee arthroplasty were included in the study, 35 patients were lost due to logistic problems. 95 patients with 124 knee prostheses had received either a TKA (primary or revision) (69 in 55 patients), a unicompartimental knee arthroplasty (7 UKA), a RHK (revision −7 in 6 patients) or a megaprosthesis (malignant bone tumours − 28 in 27 patients). The TKA, UKA and RHK groups were followed prospectively, with serum Co and Cr ions measured preoperatively, at 3,6 and 12 months postoperatively. In patients with a megaprosthesis, metal ions were measured at follow-up (cross-sectional study design).

In primary knees, we did not observe an increase in serum metal ion levels at 3, 6 or 12 months. Two patients with a hip arthroplasty had elevated preTKA Co and Cr levels. There was no difference between unilateral and bilateral knee prostheses. In the revision group, elevated pre-revision levels were found in 2 failures for implant loosening. In both cases, ion levels decreased postoperatively. In revisions with a standard TKA, there was no significant increase in metal ions compared to primary knee arthroplasty. RHK were associated with a significant increase in Co levels even at short-term (3–12 months). The megaprosthesis group had the highest metal ion levels and showed a significant increase in Co and Cr with time in patients followed prospectively. With the current data, we could not demonstrate a correlation between metal ion levels, size of the implant or length of time in situ.

In primary knee arthroplasty with a standard TKA or UKA, metal ion levels were not elevated till one year postoperatively. This suggests a different mechanism of metal ion release in comparison to metal-on-metal hip arthroplasties. In two cases of revision for implant loosening, pre-revision levels were elevated, possibly associated with component wear, and decreased after revision. With RHK, slightly elevated ion levels were found prospectively. Megaprostheses had significantly elevated Co and Cr levels, due to corrosion of large metallic surfaces and/or wear of components which were not perfectly aligned during difficult reconstruction after tumour resection. Further research is needed to assess the clinical relevance of metal ion levels in knee arthroplasty.

Total hip replacement (THR) is a common elective surgical procedure and can be effective for reducing chronic pain. However, waiting times for THR can be considerable, and patients often experience significant pain during this time. A pain self-management intervention may provide patients with the skills to enable them to manage their pain and its impact more effectively before surgery. However, studies of arthritis self-management programmes have faced challenges because of low recruitment rates, poor intervention uptake, and high attrition rates. This study aimed to evaluate the feasibility of a randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of a group-based pain self-management course for patients undergoing THR. Specific objectives were to assess trial design, ascertain recruitment and retention rates, identify barriers to participation, refine data collection methods, and evaluate uptake and patient satisfaction with the course.

Patients listed for THR in an elective orthopaedic centre Bristol, UK were sent a postal invitation about the study. Participants were randomised to attend a pain self-management course plus standard care or standard care only using a computer-generated randomisation system. The pain self-management course was delivered by Arthritis Care and consisted of two half-day group sessions prior to surgery and one full-day group session 2–4 months after surgery. A structured course evaluation questionnaire was completed by participants.

Outcomes assessment was by postal questionnaire prior to surgery and 1-month, 3-months and 6-months after surgery. Self-report resource use data were collected using a diary prior to surgery and inclusion of resource use questions in the 3-month and 6-month post-operative questionnaires. Brief telephone interviews were conducted with non-participants to explore barriers to participation.

Postal invitations were sent to 385 eligible patients and 88 patients consented to participate (23% recruitment rate). Participants had a mean age of 66 years and 65% were female. Brief interviews with 57 non-participants revealed the most common reasons for non-participation were perceptions about the intervention and difficulties in getting to the hospital for the course.

Of the 43 patients randomised to the intervention group, 28 attended the pre-operative pain self-management sessions and 11 attended the post-operative sessions. Participant satisfaction with the course was high, and patients enjoyed the group format.

Retention of participants was acceptable, with 83% completing follow-up. Questionnaire return rates were high (76–93%), with the exception of the pre-operative resource use diary (35%). Completion rates for the resource use questions varied by category and allowed for an economic perspective from the health and social care payer to be taken.

Undertaking feasibility work for a RCT is labour-intensive; however this study highlights the importance of conducting such work. Postal recruitment resulted in a low recruitment rate and brief interviews with non-participants provided valuable information on barriers to participation. Embedding collection of resource use data within questionnaires resulted in higher completion rates than using resource use diaries. While patients who attended the course gave positive feedback, attendance was low. Findings from this feasibility study enable us to design successful definitive group-based RCTs in the future.

Instability following total hip arthroplasty (THA) is an unfortunately frequent and serious problem that requires thorough evaluation and preoperative planning before surgical intervention. Prevention through optimal index surgery is of great importance, as the management of an unstable THA is challenging even for an experienced joints surgeon. However, even after well-planned surgery, a significant incidence of recurrent instability still exists. Moreover leg-length discrepancy (LLD) after THA can pose a substantial problem for the orthopaedic surgeon. Such discrepancy has been associated with complications including nerve palsy, low back pain, and abnormal gait. Consequently we may use a big femoral head or increase femoral offset (FO) in unstable THA for avoiding LLD. However we do not know the relationship between FO and STT. The objective of this study is to assess hip instability of three different FOs in same patient undergoing THA during an operation.

We performed 70 patients who had undergone unilateral THA using CT based navigation system at a single institution for advanced osteoarthoritis from May 2013 to May 2014. We used postero-lateral approach in all patients. After cup and stem implantation, we assessed soft tissue tensioning in THA during operation. Trial necks were categorized into one of three groups: standard femoral offset (sFO), high femoral offset (hFO, +4mm compared to sFO) and extensive high femoral offset (ehFO, +8 mm compared to sFO). We measured distance of lift-off about each of three femoral necks using CT based navigation system and a force gauge with hip flexed at 0 degrees and 30 degrees under a traction of lower extremity. Traction force was 40% of body weight.

Forty patients had leg length restored to within +/− 3mm of the contralateral side by post-operative CT analysis. We examined these patients. Traction force was 214±41.1Nm. The distances of lift-off were 8.8±4.5mm (sFO), 7.4±4.1mm (eFO), 5.1±3.9mm (ehFO) with 0 degrees hip flexion and neutral abduction(Abd) / adduction(Add) and neutral internal rotation(IR)/ external rotation(ER). The distance of lift-off were 11.5±5.9mm (sFO),10.5±5.5mm (eFO),9.1±5.9mm (ehFO) with 30 degrees hip flexion and neutral Abd / Add and neutral IR/ER. Significant difference was observed between 0 degrees hip flexion and 30 degrees hip flexion on each FO (p<0.05). On changing the distance of lift-off, hFO to ehFO (2.2±1.6mm)was more stable than sFO to hFO (1.4±1.7mm)with 0degrees hip flexion.(p<0.05). On the other hands, hFO to ehFO (1.4±1.6mm) was more stable than sFO to hFO (1.0±1.3mm) with 30 degrees hip flexion. However, we did not find significant difference (p=0.18).

Hip instability was found at 30 degrees hip flexion more than at 0 degrees hip flexion. We found that changing ehFO to sFO can lead to more stability improvement of soft tissue tensioning than sFO to eFO, especially at 0 degrees hip flexion. Whereas In a few cases, the distance of lift-off did not change with increasing femoral offset by 4mm. When you need more stability in THA without LLD, We recommend increasing FO by 8mm.

Heterotopic ossi?cation is the abnormal formation of bone in soft tissues and is a frequent complication of hip replacement surgery. Heterotopic ossi?cations are described to develop via endochondral ossification and standard treatment is administration of indomethacin. It is currently unknown how indomethacin influences heterotopic ossi?cation on a molecular level, therefore we aimed to determine whether indomethacin might influence heterotopic ossi?cation via impairing the chondrogenic phase of endochondral ossification.

ATDC5, human bone marrow stem cells (hBMSCs) and rabbit periosteal agarose cultures were employed as progenitor cell models; SW1353, human articular chondrocytes and differentiated ATDC5 cells were used as matured chondrocyte cell models. All cells were cultured in the presence of (increasing) concentrations of indomethacin. The action of indomethacin was confirmed by decreased PGE2 levels in all experiments, and was determined by specific PGE2 ELISA. Gene- and protein expression analyses were employed to determine chondrogenic outcome.

Progenitor cell models differentiating in the chondrogenic lineage (ATDC5, primary human bone marrow stem cells and ex vivo periosteal agarose cultures) were treated with increasing concentrations of indomethacin and a dose-dependent decrease in gene- and protein expression of chondrogenic and hypertrophic markers as well as decreased glycosaminoglycan content was observed. Even when hypertrophic differentiation was provoked the addition of indomethacin resulted in decreased hypertrophic marker expression. Interestingly, when mature chondrocytes were treated with indomethacin, a clear increase in collagen type 2 expression was observed. Similarly, when ATDC5 cells and bone marrow stem cells were pre-differentiated to obtain a chondrocyte phenotype and indomethacin was added from this time point onwards, low concentrations of indomethacin also resulted in increased chondrogenic differentiation.

Indomethacin induces differential effects on in vitro endochondral ossification, depending on the chondrocyte's differentiation stage, with complete inhibition of chondrogenic differentiation as the most pronounced action. This observation may provide a rationale behind the elusive mode of action of indomethacin in the treatment of heterotopic ossifications.

NK cells participate in the control of infection and cell transformation but, on the other hand, they are involved in the pathology of different inflammatory disorders. Recent evidences suggest that inflammation is an important regulator of osteoarthritis, but the mechanism and cells responsible of inflammation maintenance are not well defined.

To understand the role of NK cells in osteoarthritis, we have performed a preliminary study to compare the phenotype and function of peripheral blood with synovial fluid NK cells from 49 patients with osteoarthritis undergoing total knee arthroplasty. A phenotype analysis of NK cells were carried out by flow cytometry using lineage surface marker. For the first time, the expression of granzyme A, granzyme B and perforin was also performed. Finally, cytotoxicity assays were carried out using previously isolated NK cells co-cultured with their natural target K562 cells.

The majority of NK cells from the synovial fluid were CD56brightCD16negative cells. Moreover, CD56brightCD16negative cells present in synovial fluid showed higher expression of granzyme A and low expression of granzyme B and perforin. In addition, and in contrast to NK cells isolated from the peripheral blood, synovial NK cells were not able to kill K562 cells.

Our results indicate that NK cells from the synovium of patients with osteoarthritis, which present an immunoregulatory non-cytotoxic phenotype, show a different to phenotype of NK cells from peripheral blood, preferably expressing granzyme A, a pro-inflammatory molecule which may contribute to the establishment of chronic articular inflammation in this type of patients.

Adult chondrocytes experience a hypoxic environment in vivo. Culturing chondrocytes under oxygen tension that more closely resembles the in vivo situation, i.e. hypoxic conditions, has been shown to have positive effects on matrix synthesis. During redifferentiation of expanded chondrocytes, hypoxia increased collagen type II expression. However, the mechanism by which hypoxia enhances redifferentiation is still incompletely elucidated. We employed micro-bioreactor technology to elucidate the contribution of TGF-β superfamily ligands to the chondrocyte differentiation process under hypoxic conditions in vitro.

Dedifferentiated chondrocytes in alginate were cultured for 48 hours under hypoxic (1% pO2) or normoxic (20%) conditions, using specialized bioreactor technology. Gene expression of chondrocyte-specific markers (SOX9, COL2A1, COL1A1, AGC1 and MMP13) as well as established hypoxia-controlled genes (GDF1-, PHD3, HAS2, VEGF, COX2) and components of the TGF-β superfamily signaling pathways were analyzed by qPCR and protein expression after 48 hours in combination with TGF-β superfamily ligand-specific siRNA as well as selected TGF-β superfamily receptor inhibitors.

Hypoxic culture showed robust upregulation of the selected hypoxia-specific marker genes. In addition, well-established chondrocyte-specific markers like SOX9 and collagen type II were upregulated. TGF-β isoforms were selectively upregulated under hypoxia on both mRNA and protein level. In addition, both Activin receptor-like kinases, ALK1 and ALK5, were upregulated under hypoxia, while respective type II and III receptors were unresponsive. The hypoxia-induced COL2 expression was abrogated by TGF-β2 siRNA, as was ALK5 inhibition. Our data strongly indicates that TGF-β superfamily signaling pathways are involved in chondrocyte redifferentiation under low oxygen tension in vitro.

Osteonecrosis of the femoral head is a complex pathologic process with many aetiological factors. Factors most often mentioned in the literature are mechanical disruption (hip trauma or surgery), steroid use, smoking, haemoglobinopathies and hyperlipidaemia.¹ Our case depicts a rare association of crack cocaine related to osteonecrosis of the femoral head which has never been reported in the available literature.

Case Report: A 32 year old man was referred to our Orthopaedic clinic with right hip pain. He had a 9 pack-year history of cigarette smoking and had also smoked crack cocaine between ages 20 to 28; shortly after this the hip pain started. He denied antecedent injury. He had undergone a steroid injection into his right ankle abroad for swelling one year before referral, which was after onset of hip pain. MRI of his hip previously performed abroad had been normal. The patient had an indoor job and was otherwise fit and well. On examination he had reduced of movement in his right hip with 5–10 degrees of fixed flexion deformity. Plain radiography demonstrated cyst formation and sclerosis of both femoral heads. Repeat MRI confirmed bilateral osteonecrosis, worse on the right with risk of head collapse. The patient underwent bilateral core decompressions. Subsequent follow-up demonstrated a mobile patient with no need for arthroplasty and he was discharged after two years.

Osteonecrosis is caused by the coagulation of the intra-osseous microcirculation leading to thrombosis formation and eventual reduction in osseous blood supply. Steroid use is associated with increased risk of osteonecrosis to the femoral head, however in these cases the patients often undergo either direct local or systemic infiltration of steroid. In this case steroid was administered after symptoms began to a far distant site and therefore cannot be the cause. Cigarette smoking is also known to cause osteonecrosis. Our patient had smoked cigarettes for fourteen years without problems, and it was after he ceased to smoke crack cocaine that his symptoms began. Cocaine blocks voltage-gated sodium-channels causing vasospasm. It is known to cause nasal and facial bone osteonecrosis due to its common intranasal method of delivery.

We postulate that in this case crack cocaine was a synergistic factor towards development of femoral head osteonecrosis.

Polymer foams have been used extensively in the testing and development of orthopaedic devices and for verification of computational models. Their use is often preferred over cadaver and animal models due to being relatively inexpensive and their consistent material properties. Successful validation of such models requires accurate material/mechanical data. The assumed range of compressive moduli, provided in the sawbones technical sheet, is 16 MPa to 1.15 GPa depending on the density of foam. In this investigation, we apply two non-contact measurement techniques (digital volume correlation (DVC) and optical surface extensometry) to assess the validity of these reported values. It is thought that such non-contact methods remove mechanical extensometer errors (slippage, misalignment) and restrict the effect of test-machine end-artifacts (friction, non-uniform loading, platen flexibility). This is because measurement is taken directly from the sample, and hence material property assessment should be more accurate. Use of DVC is advantageous as full field strain measurement is possible, however test time and cost is significantly higher than extensometry. Hence, the study also sought to assess the viability of optical extensometry for characterising porous materials.

Testing was conducted on five 20 mm cubic samples of 0.32g/cc (20 pcf) solid rigid polyurethane foam (SAWBONES^TM). The strain behaviour was characterised by incremental loading via an in situ loading rig. Loading was performed in 0.1 mm increments for 8 load steps with scans between loading steps. Full field strain measurement was performed on one sample by micro focus tomography (muvis centre, Southampton) and subsequent DVC (DaVis, Lavision). Calculation of Young's modulus and Poisson's ratio was then preformed through use of the virtual fields method. These results were subsequently corroborated by use of optical extensometry (MatchID). To account for heterogeneities, axial strain measurements were averaged from six points on the front and rear surfaces. A computationally derived correction factor was then applied to account for through volume strain variations. In each test compressive displacement was applied to 900N (∼2MPa) to remain within the linear elastic region.

Significant variability of individual strain measurements were observed from extensometry measurements on the same sample, indicating non-uniform loading did occur in all samples. However by averaging across multiple points linear loading profiles were identified. For all non-contact methods the calculated elastic moduli were found to range between 331–428 MPa whilst the approximated modulus based on cross head displacement was ∼210 MPa. The optical-extensometry gave a considerably higher modulus (p = 0.047) than the DVC results as only surface measurements were made. However, following computational based correction values converged within 6% of one another. Both the DVC and point-tracking results (p = 0.001) indicated substantially higher compressive modulus (137%) than the manufacturer provided properties.

This study demonstrates that methods of measuring displacement data on of cellular foams must be carefully considered, as artefacts can lead to significant errors of up to 137%, and such errors may falsely influence the design and validation of tested devices.

Osteoarthritis (OA), the most common chronic degenerative joint disease, is characterized by inflammation, degradation of the articular cartilage and subchondral bone lesions, causing pain and decreased functionality.

NF-κB pathway is involved in OA and, in most cases, its activation depends on the phosphorylation and degradation of IκBα, the NF-κB endogenous inhibitor that sequesters NF-κB in the cytosol. Under inflammatory stimuli, IκBα is degraded by the IKK signalosome and NF-κB moves into the nucleus, inducing the transcription of inflammatory mediator genes and catabolic enzymes. The IKK signalosome includes IKKβ and IKKα kinases, the latter shown to be pivotal in the OA extracellular matrix derangement. The current OA therapies are not curative and nowadays, the preclinical research is evaluating new structure-modifying pharmacological treatments, able to prevent or delay cartilage degradation.

N-acetyl phenylalanine derivative (NAPA), is a derivative of glucosamine, a constituent of the glycosaminoglycans of cartilage and a chondroprotective agent. Previous in vitro studies showed the ability of NAPA to increase cartilage components and to reduce inflammatory cytokines, inhibiting IKKα kinase activity and its nuclear migration.

The present study aims to further clarify the effect of NAPA in counteracting OA progression, in an in vivo mouse model after destabilization of the medial meniscus (DMM).

Mice were divided into 3 groups:

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DMM group: DMM surgery without NAPA;

DMM surgery was performed in the right knee, according to Glasson SS [2], while the left knee did not undergo any surgery. Four weeks after surgery (mild-to-moderate OA), some animals received one intra-articular injection of NAPA (2.5 mM) and after 2 weeks, the animals were pharmacologically euthanized. The mice of the 1^st group were euthanized 4 weeks after DMM and those of the 3^rd group after 6 weeks from their arrival in the animal facility. At the end of experimental times, both knee joints of the animals were analyzed through histology, histomorphometry, immunohistochemistry and subchondral bone microhardness.

The injection of NAPA significantly improved cartilage structure, increased cartilage thickness (p<0.0005), reduced Chambers and Mankin scores (p<0.005), fibrillation index (p<0.005) and decreased MMP13 (p<0.05) and ADAMTS5, MMP10, and IKKα (p<0.0005) staining. The microhardness measurements did not shown statistically significant differences between groups.

This study demonstrated the chondroprotective activities exerted by NAPA in vivo. NAPA markedly improved the physical structure of articular cartilage and reduced the amount of catabolic enzymes, and therefore of extracellular matrix remodeling. The reduction in OA grading and catabolic enzymes paralleled the reduction of IKKα expression. This further hints at a pivotal role of IKKα in OA development by regulating MMP activity through the control of procollagenase (MMP10) expression. We believe that the preliminary preclinical data, here presented, contribute to improve the knowledge on the development of disease modifying drugs since we showed the ability of NAPA of reverting the surgically induced OA in the widely accepted DMM model.

Medial meniscus tear has been proposed as a potential etiology of spontaneous osteonecrosis of the knee (SONK). Disruption of collagen fibers within the meniscus causes meniscal extrusion, which results in alteration in load distribution in the knee. A recent study has demonstrated high incidence of medial meniscus extrusion in the knee with SONK. Our purpose was to determine whether the extent of medial meniscus extrusion correlates with the severity of SONK in the medial femoral condyle.

Anteroposterior and lateral knee radiographs were taken with the patients standing. Limb alignment was expressed as the femorotibial angle (FTA) obtained from the anteroposterior radiograph. The stage of progression of SONK was determined according to the radiological classification system described by Koshino. After measurement of anteroposterior, mediolateral, and superoinferior dimensions of the hypointense T1 signal intensity lesion of MRI, its ellipsoid volume was calculated with the three dimensions. Meniscal pathology (degeneration, tear, and extrusion) were also evaluated by MRI.

Of the 18 knees with SONK, we found 5 knees at the radiological stage 2 lesions, 9 knees at the stage 3, and 4 knees at the stage 4. Whereas the ellipsoid volume of SONK lesion significantly increased with the stage progression, the volume was significantly greater at stage 4 than stage 2 or 3. All the 18 knees with SONK in the present study showed substantial extrusion (> 3mm) and degeneration of the medial meniscus. While medial meniscal extrusion increased with the stage progression, medial meniscus was significantly extruded at stage 3 or 4 compared with stage 2. A significant increase in FTA was found with the stage progression. FTA was significantly greater at stage 4 than stage 2 or 3. Multiple linear regression analysis revealed that medial meniscus extrusion and FTA were useful predictors of the volume of SONK lesion.

This study has clearly shown a significant correlation between the extent of medial meniscus extrusion and the stage and volume of SONK lesion. Degeneration and tears of the medial meniscus in combination with extrusion may result in loss of hoop stress distribution in the medial compartment, which could increase the load in the medial femoral condyle. In addition to meniscal pathology, knee alignment can influence load distribution in the medial compartment biomechanically. Multiple linear regression analysis indicates that an increase in FTA concomitant with a greater extrusion of medial meniscus could result in greater lesion and advanced radiological stage of SONK. Taken together, alteration in compressive force transmission through the medial compartment by meniscus extrusion and varus alignment could develop subchondral insufficiency fractures in the medial femoral condyle, which is considered to be one of the main contributing factors to SONK development.

There was high association of medial meniscus extrusion and FTA with the radiological stage and volume of SONK lesion. Increased loading in the medial femoral condyle with greater extrusion of medial meniscus and varus alignment may contribute to expansion and secondary osteoarthritic changes of SONK lesion.

Anterior cruciate ligament (acl) reconstruction is one of the most commonly performed procedures in orthopedics for acl injury. While literature suggest short-term good-to-excellent functional results, a significant number of long-term studies report unexplained early oa development, regardless type of reconstruction. The present study reports the feasibility analysis and development of a clinical protocol, integrating different methodologies, able to determine which acl reconstruction technique could have the best chance to prevent oa. It gives also clinicians an effective tool to minimize the incidence of early oa.

A prospective clinical trial was defined to evaluate clinical outcome, biochemical changes in cartilage, biomechanical parameters and possible development of oa. The most common reconstruction techniques were selected for this study, including hamstring single-bundle, single-bundle with extraarticular tenodesis and anatomical double-bundle. Power analysis was performed in terms of changes at cartilage level measurable by mri with t2 mapping. A sample size of 42 patients with isolated traumatic acl injury were therefore identified, considering a possible 10% to follow-up. Subjects presenting skeletal immaturity, degenerative tear of acl, other potential risk factors of oa and previous knee surgery were excluded. Included patients were randomized and underwent one of the 3 specified reconstruction techniques. The patients were evaluated pre-operatively, intra-operatively and post-operatively at 4 and 18 months of follow-up. Clinical evaluation were performed at each time using subjective scores (koos) and generic health status (sf-12). The activity level were documented (marx) as well as objective function (ikdc).

Preliminary results allow to verify kinematic patterns during active tasks, including level walking, stair descending and squatting using dynamic roentgen sterephotogrammetric analysis (rsa) methodology before and after the injured ligament reconstruction. Intra-operative kinematics was also available by using a dedicated navigation system, thus to verify knee laxity at the time of surgery. Additionally, non-invasive assessment was possible both before the reconstruction and during the whole follow-up period by using inertial sensors. Integrating 3d models with kinematic data, estimation of contact areas of stress patterns on cartilage was also possible.

The presented integrate protocol allowed to acquired different types of information concerning clinical assessment, biochemical changes in cartilage and biomechanical parameters to identify which acl reconstruction could present the most chondroprotective behavior. Preliminary data showed all the potential of the proposed workflow. The study is on-going and final results will be shortly provided.

Autologous bone grafting is a standard procedure for the clinical repair of skeletal defects, and good results have been obtained. Autologous vascularized bone grafting is currently the procedure of choice because of high osteogenic potential and resistance against reabsorption. Disadvantages of this procedure include limited availability of donor sites, clinical difficulty in handling, and a failure rate exceeding 10%. Allografts are often used for massive bone loss, but since only the marginal portion is newly vascularized after the implantation non healing fractures are often reported, along with a graft reabsorption. To overcome these problems, some studies in literature tried to conjugate bone graft and vascular supply, with encouraging results. On the other side, several studies in literature reported the ability of bone marrow derived cells to promote neo-vascularization. In fact, bone marrow contains not only hematopoietic stem cells (HSCs) and MSCs as a source for regenerating tissues but also accessory cells that support angiogenesis and vasculogenesis by producing several growth factors. In this scenario a new procedure was developed, consisting in an allogenic bone graft transplantation in a critical size defect in rabbit radius, plus a deviation at its inside of the median artery and vein with a supplement of autologous bone marrow concentrate on a collagen scaffold.

Twenty-four New Zealand male white rabbits (2500–3000 g) were divided into 2 groups, each consisting of 12 animals. Surgeries were performed as follow:

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Group 1 (#12): allogenic bone graft (left radius) / allogenic bone graft + vascular pedicle + autologous bone marrow concentrate (right radius)

For each group, 3 experimental time: 8, 4 and 2 weeks (4 animals for each time).

The bone used as graft was previously collected from an uncorrelated study. An in vitro evaluation of bone marrow concentrate was performed in all cases, and at the time of sacrifice histological and histomorphometrical assessment were performed with immunohistochemical assays for VEGF, CD31 e CD146 to highlight the presence of vessels and endothelial cells. Micro-CT Analysis with quantitative bone evaluation was performed in all cases.

The bone marrow concentrate showed a marked capability to differentiate into osteogenic, chondrogenic and agipogenic lineages. No complications such as infection or intolerance to the procedure were reported. The bone grafts showed only a partial integration, mainly at the extremities in the group with vascular and bone marrow concentrate supplement, with a good and healthy residual bone. immunohistochemistry showed an interesting higher VEGF expression in the same group. Micro CT analysis showed a higher remodeling activities in the groups treated with vascular supplement, with an area of integration at the extremities increasing with the extension of the sacrifice time.

The present study suggests that the vascular and marrow cells supplement may positively influence the neoangiogenesis and the neovascularization of the homologous bone graft. A longer time of follow up and improvement of the surgical technique are required to validate the procedure.

Mesenchymal stem cells (MSCs) are believed to be immune-privileged due to lack of antigen-presenting-cell related markers, however, evidence suggests that MSCs are immunogenic and are attacked by the immune system. Our research investigates the hypothesis that there are differences between MSC clones from the same individual in terms of their morphology, proliferation, differentiation and immune profile. Our goal is to discover immune-privileged stem cells, which can act as a universal allogenic mesenchymal stem cell donor to facilitate bone ingrowth for osteosarcoma patients status post tumor excision and prosthesis implantation.

Serial dilutions of bone-marrow derived (BMMSCs) and adipose derived mesenchymal stem cells (ADMSCs) from same animal were carried out in order to isolate single-cell clones. From a single animal we obtained 3 clones from BMMSCs and 3 from ADMSCs. This procedure was repeated for another other 2 animals. The proliferation rate and cell doubling time of each clonal culture was measured. The proliferation rate of mixed clonal cultures was also measured. The tri-differentiation potential of the clonal cultures was compared and a comparison was also made with the original isolates from bone marrow and fat. The immune-privileged properties were measured by flow cytometry and immuno-staining for the major histocompatibility complex (MHC) antigens. To measure the immune response a mixed leucocyte reaction was used but where leucocytes from a different individual were mixed with the clonal MSC cells.

All isolates were able to differentiate into osteoblasts, chondrocytes and adipocytes. All clonal cultures revealed significantly different proliferation rates and doubling times when compared with each other and with mixed cultures. All clonal cultures showed different surface marker presentations, which included differences in the expression of MHC antigens. One clone isolated from ADMSCs showed lack of MHCI and MHCII. Our mixed leucocyte reaction and MHC staining showed variety of immune-modulation and this was related to the expression of the MHC antigens.

All clones tri-differentiated and therefore show a degree of ‘stemness’. MSCs are generally are believed not to express MHC II and to be immune-privileged. However, this study shows that the expression of these antigens in clones isolated from bone marrow and from fat is variable. A heterogeneous result indicates individual differences between MSCs, even from same origin. The immune response elicited by MSCs is complicated. MSCs have been shown to release interleukin 10, which could inhibit the immune response but on the other hand interferon-gamma could enhance MHCII presentation in some MSCs. Our results confirmed our hypothesis because clonal cultures isolated from different sources of MSCs in the same animal showed significant differences in proliferation rate, morphology and surface marker presentation. Mesenchymal stem cells are not immunogenic or immune-privileged. Individual differences highlighted through single-cell clonal cultures may be the key to finding a universal immune-privileged MSCs for allogeneic transplantation.

Demineralized bone matrix (DBM) is a natural, collagen-based, well-established osteoinductive biomaterial. Nevertheless, there are conflicting reports on the efficacy of this product. The purpose of this study was to evaluate whether DBM collagen structure is affected by particle size and can influence DBM osteoinductivity.

Sheep cortical bone was ground and particles were divided in three fractions with different sizes, defined as large (L, 1–2 mm), medium (M, 0.5–1 mm), and small (S, < 0.5 mm). After demineralization, the three DBM samples were characterized by DTA analysis, XRD, ICP-OES, and FTIR. Data clearly showed a particle size-dependent alteration in collagen structure, with DBM-M being altered but not as much as DBM-S. The in vivo study showed that only DBM-M was able to induce new bone formation in a subcutaneous ectopic mouse model. When sheep MSC were seeded onto DBM particles before implantation, all DBM particles were able to induce new bone formation with the best incidence for DBM-M and DBM-S. Gene expression analysis performed on recovered implants supports the histological results and underlines the supportive role of MSC in DBM osteoinduction through the regulation of host cells. In conclusion, our results show a relation between DBM particle size, structural modification of the collagen and in vivo osteoinductivity. The medium particles represent a good compromise between no modification (largest particles) and excessive modification (smallest particles) of collagen structure, yielding highest osteoinduction. We believe that these results can guide researchers to use DBM particles of 0.5–1 mm size range in applications aimed at inducing new bone formation, obtaining results more comparable and reliable among different research groups. Furthermore, we suggest to carefully analyze the structure of the collagen when a collagen-based biomaterial is used alone or in association with cells to induce new bone formation.

Maintenance of acid-base homeostasis in extracellular fluids and in the cytoplasm is essential for the physiological activities of cells and tissues [1]. However, changes in extracellular pH (pHe) occurs in a variety of physiological and pathological conditions, including hypoxia and inflammation associated with trauma and cancer. Concerning bone tissue, if abnormal acidification occurs, mineral deposition and osteoblast differentiation are inhibited, whereas osteoclast formation and activity are enhanced [2]. Indeed, acidification, that usually occurs in the early phases of fracture repair, has been suggested as a driving force for regeneration via release of growth factors that act on the stem cell fraction of repair bone [3]. However, the effect of low pHe on stemness has been insufficiently explored so far. Thus, in this study, we investigated the role of short term exposure to low pHe (6.5–6.8) on MSC stemness.

MSC derived from dental pulps (DPSC) and bone marrow (BM-MSC) were used. To perform the specific assays, culture medium at specific pH (6.5, 6.8, 7.1 and 7.4) was maintained by using different concentrations of sodium bicarbonate according to the Henderson-Hasselbach equation.

Changes in osteoblast-related gene expression (COL1A1 and ALPL), and mineral nodule formation were measured by qRT-PCR and Alizarin red staining, respectively.

The stem phenotype was analysed by measuring changes in stemness-related genes (SOX2, OCT4, KLF4, c-MYC) expression and spheres forming ability. Additionally, cell number, Ki67 index and cell cycle were analysed to monitor cell proliferation and quiescence.

We confirmed that acidic pHe inhibits the osteogenic differentiation of DPSC. Low pHe significantly but transitorily decreased the expression of osteoblast-related genes (COL1A1 and ALPL) and decreased the mineral nodule formation in vitro.

Acidic pHe conditions significantly increased the ability of DPSC and BM-MSC to form floating spheres. At acidic pHe spheres were higher but smaller when compared to spheres formed at alkaline pHe conditions. Moreover, acidic pHe increased significantly the expression of stemness-related genes. Finally, low pHe induced a significant decrease of DPSC cell number. Reduction of cell proliferation correlated with a lower number of cycling cells, as revealed by the Ki67 index that significantly decreased in a pH-dependent manner. Cell cycle analysis revealed an accumulation of cells in the G0 phase, when cultured at low pH.

In this study, we demonstrated a close relationship between acidic pHe and the regulation of MSC stemness. We therefore suggest that pHe modulation of MSC stemness is a major determinant of skeletal homeostasis and regeneration, and this finding should be considered in bone healing strategies based on cell therapy.

Intermittent parathyroid hormone 1–34 (teriparatide) is the N-fragment terminal of the intact hormone, currently in clinical use to treat osteoporosis. Unlike anti-catabolic agents such as bisphosphonates, PTH 1–34 not only affects the osteoclast, but also up regulates bone formation via both modelling and remodelling mechanisms. The actions of iPTH on mesenchymal stem cell differentiation (MSCs) may underpin a further method in the treatment of osteoporosis specifically, and for fracture healing in general. Stem cells from older female osteoporotic animals have reduced activity and poorer osteogenic potential; additionally, their migration to and retention at sites of increased bone turnover are reduced in comparison to cells from younger animals. The aim of this study was to isolate bone marrow derived MSCs from both young Wild Type (WT) and ovarectomized senile (OVX) rats, then to investigate and compare the effect of pulsatile and continuous PTH administration on migration to SDF-1, proliferation and osteogenic differentiation.

MSCs were harvested from the femora of 6–9week Wistar rats, and from 10–13month ovarectomized rats with established osteopenia. Cells were cultured with 25, 50 and 100nmMol of PTH 1–34 added to osteogenic media either continuously or in a pulsatile fashion for 6 hours in every 72hour cycle. ALP and Alizarin Red were used to assess the optimal concentration of PTH for osteogenic differentiation. Subsequently, proliferation was assessed with Alamar Blue and cells were seeded in a Boyden chamber to quantify the migration to SDF-1. As the data was parametric a student t-test was used to analyse results, and a p value < 0.05 was considered significant.

ALP and Alizarin Red parameters were significantly increased for both WT and OVX groups at 50nmMol of pulsatile PTH in comparison to groups cultured in 25 or 100nmMol. Continuous administration at all concentrations led to reduced calcium phosphate deposition by day 21 in all groups. Interestingly, in comparison to cells cultured in osteogenic media, 50nmMol of pulsatile PTH lead to statistically significant higher ALP and Alizarin Red measurements up to day 10 and 14 respectively in WT cells, and days 10 and 21 in OVX cells. The proliferation rate normalised against DNA was similar for both OVX and WT rats at all-time points. PTH administration did not effect cell proliferation in any group. WT MSCs not only had improved osteogenic differentiation, but also showed increased migration to SDF-1 in comparison to OVX groups. Pulsatile PTH led to further increases in migration of both OVX and WT cells.

Intermittent PTH increases the osteogenic diffrentiation and migration of MSCs from both young and ovarectomised rats, though importantly this effect is not dose dependent. Ultimately, the role of PTH 1–34 on MSCs may lead to improved bone formation and cell homing capacity-particularly in the context of osteoporosis.

Among the very large number of polymeric materials that have been proposed in the field of orthopedics, polyethylene terephthalate (PET) is one of the most attractive thanks to its flexibility, thermal resistance, mechanical strength and durability. Several studies were proposed that interface nano- or micro-structured surfaces with mesenchymal stromal cells (MSCs), demonstrating the potential of this technology for promoting osteogenesis. All these studies were carried out on other biomaterials than PET, which remains almost un-investigated in terms of cell shaping, alignment and differentiation. In a previous study, we developed a hot-embossing method to transfer nano-textures (down to below 100 nm lateral size) onto PET substrate, and demonstrated that PET nanogratings (NGs) can optimally stimulate hMSC mechanotransduction mechanism. Specifically, we showed that cell and nuclear morphology, and cytoskeletal components are similarly affected by NGs, and that NG ridge sizes of 500 nm and 1 μm were both effective in stimulating cell polarization, without compromising cell viability.

We study the effect of PET 350-depth nanogratings (NGs) having ridge and groove lateral size of 500 nm (T1) or 1 µm (T2), on bone-marrow human MSC (hMSC) differentiation towards the osteogenic fate. In particular, we cultured hMSCs on PET NGs having different periodicity and measured the expression of a complete set of genes characterizing osteo-differentiation, at different time-points from day 3 up to day 21. In order to evaluate how the contact interaction with PET NGs affects hMSC differentiation, the expression of a set of genes (RUNX2, COL1A1, ALPL, BMP2 and IBSP) characterizing osteogenesis was measured by RT-qPCR. BMP2 and IBSP were the most sensitive to the presence of the engineered surfaces The production of bone matrix was finally evaluated at the end of the differentiation period in terms of morphology, substrate coverage and alignment to the underlying topography.

Overall, the data show that among the tested genes, BMP2 and IBSP are the most sensitive to the presence of the engineered surfaces. Although for RUNX2, COL1A1 and ALPL we measured only small modifications, upregulation of BMP2 and IBSP was relevant, especially in case of Osteogenic Medium (OM) and for the T2 geometry. This result suggests the T2 substrate as the most promising structure for stimulating hMSCs towards osteogenic maturation

We demonstrate that these substrates, especially the T2, can promote the osteogenic phenotype more efficiently than standard flat surfaces and that this effect is more marked if cells are cultured in osteogenic medium than in basal medium. Finally, we show that the shape and disposition of calcium hydroxyapatite granules on the different substrates was influenced by the substrate symmetry, being more elongated and spatially organized on NGs than on flat surfaces.

This study demonstrates that PET nanogratings can promote osteogenic differentiation of hMSC in vitro. Since PET is an FDA approved material and we did not use any surface chemical treatment for cell adhesion and spreading, PET NGs can be considered promising for clinical translation in the field of orthopedic tissue engineering.

Allografts are used to compensate for bone defects resulting from revision surgery, tumor surgery and reconstructive bone surgery. While it is well known that the reduction of fat content of allografts increases mechanical properties, the content of liquids were not assessed with known grain size distribution so far. The aim of the study was to compare the mechanical properties of dried allografts (DA) to allografts mixed with a saline solution (ASS) to allografts mixed with blood (AB) having a similar grain size distribution.

Fresh-frozen morsellized bone chips were cleaned chemically, sieved and reassembled in specific portions with known grain size distribution. A uniaxial compression was used to assess the yield limit of the three groups before and after compaction with a fall hammer apparatus.

No statistically significant difference could be found between all three groups for the yield limit (p=0.339) before compaction. After compaction no statistically significant difference could be found between DA and ASS (p=0.339) and between ASS and AB (p=0.554). AB showed a statistically significant higher yield limit than DA (p=0.022). At the yield limit 3 outliers were removed in DA, 1 in ASS and 1 in AB before compaction and 2 in DA and 1 in AB after compaction.

Excluding the effect of the grain size distribution on the mechanical properties it was shown that allografts have a lower yield limit, when lipids are present. The liquid content of allografts seems to play an inferior role as no statistically significant difference could be found between DA and ASS. It is suggested in accordance with other studies to chemical clean allografts before implantation to reduce the contamination risk and the fat content. An optimum liquid level still remains to be defined. The considerations here described are relevant for filling up bigger bone defects, while in smaller defects the differences between different preparation methods may be less prominent.

Angiogenesis is a key factor in early stages of wound healing and is crucial for tissue regeneration. Gold standard for large bone defect treatment is the transplantation of autologous bone grafts, but is not entirely satisfying (e.g. limited amount). Cell therapies and tissue engineering approaches may overcome these problems by using cells and autologous blood components obtainable by less invasive procedures. Pre-clinical studies previously showed promising results combining endothelial progenitor cells (EPCs) and mesenchymal stem cell (MSCs) in polyurethane scaffolds in presence of PRP (1). A systemic investigation of the chemical and mechanical characteristics of different PRP gels formulations suggested their potential use as sustained autologous growth factor delivery system (2). Here we investigate PRP hydrogels as autologous injectable cell delivery systems for EPCs and MSCs and their efficacy in promoting fast neo-vascularization for bone repair applications.

PRP hydrogel and corresponding platelet lysate (PL) were produced from platelet concentrates as described before (3). MSCs were isolated by Ficoll-Paque centrifugation from human bone marrow (EK_regensburg12-101-0127), and cultured in alpha MEM containing 10% FCS and 5 ng/mL basic-FGF (GIBCO). EPCs (CD133+/CD34+) were isolated from MSC fractions using magnetic-activated cell sorting (MACS®) and further cultured in IMDM (GIBCO) containing 5% FCS and 5% PL. GFP positive HUVECs are from Angio-Proteomie, (Boston, USA). Prior to gel encapsulation, MSC and EPCs were pre-stained using PKH26-red® and PKH67-green® respectively. Cells in different proportions were encapsulated in 3D PRP gels, in FDA approved Fibrin gels and in Matrigel®. The gels were cultured in Ibidi microwells placed in an onstage incubator linked to an EVOS Auto Cell Imaging System. The cellular network formation capacity of HUVEC or EPCs and MSC in different proportions was analyzed for the 3 types of hydrogels using time lapse movies recorded over a period of 14 days. Parallel cultures were performed in a classical cell culture CO₂ incubator and sample gels were taken at different time points for additional immunostaining and gene expression analysis.

Preliminary results indicate high cell viability in all of the three tested gels. PRP hydrogels present a favorable environment for the formation of a 3 dimensional cellular network in cell co-culture. The formation of these networks was apparent as early as 4 days after seeding. Networks increase in complexity and branching over time. The same was observed when cells were embedded in Matrigel®, which is known for its pro-angiogenic properties. Further experiments are currently in process looking at the involvement of MSCs in this process and the effect of PRP 3D co-culture on their differentiation.

PRP was previously shown as a potent growth factor delivery system for tissue engineering. In the present work, the high cell viability together with the 3 dimensional capillary-like networks observed at early time points suggest that PRP can also be used as an autologous cell delivery and pro-angiogenic system for bone tissue repair.

Shortness of an extremity due to different causes is an issue that may adversely affect human life functional and psychologically. In this study, in the light of previous studies, it is aimed to develop a new expandable intramedullary system, providing lengthening in order to remove previous problems and complications and to annihilate leg length discrepancies at present and future without second surgical intervention as far as possibble by lenghtening the intramedullary nail. To this end, a new electromechanically activated intramedullary nail has been designed and generated.

The intramedullary nail was designed to perform extremity lengthening electro-mechanically. The 3D design of the system is performed with computer software and the rapid and metal prototype of the system has been produced. The intramedullary nail system is comprised of three main units; Mechanical transmission unit, Electronic unit, Lengthening unit. The nail system is designed to function both mechanically and electronically complying with the requirement. This also provides an advantage that if any one (mechanic or electronic) fails, the lengthening process can continue with the other.

Compression tests are applied in order to evaluate the strength of the system. The deformation values of the parts are recorded and stress values of each parts were calculated.

The new system needs only 300N loading for mechanical lengthening. When 800N is considered as average human weight, the implant must withstand minumum 2400N load. Considering the safety conditions, we applied 4000N load on the new system. At 4000N, the whole system shows only 1.465 mm deformation which is less than the gap between the two bone parts. Also, when the system is implanted inside the bone, the loads are distributed proportionally between the bone and the implant. So, except for extraordinary conditions, the newly developed system is highly rigid and safe.

In each applied method, lots of complications whether general or method-specific are seen. When the methods like Albizzia, ISKD and FITBONE avaliable and widely used today are examined separately, complications specific to these methods can be clearly observed [1–12].

Bliskunov Nail, Albizzia Nail and ISKD [13–18] have mechanical working principles and in these systems, lengthening process is obtained by rotational movement of the extremity. This rotational movement causes complications like pain, dislocation and uncontrolled lengthening [11,13,16,19–21]. In our newly developed system, only axial stimulation is needed for the activation of the mechanism. This is one of the advantages of our system. Both the mechanical unit and the electronical units are designed to be extended 0.1 mm at each activation. This means that the optimal amount of distraction (1mm/day) can be achieved in a controlled way. In other systems, the distraction amount can not be fully controlled and complications seen on other systems [1, 6, 8–10], like distruption of callus due to the excessive distraction and nonunion of the bone can be encountered

The success of the system at practice will be examined with in-vivo animal experiments and according to the results, it will be ready for use on human by performing necessary restorations.

Prosthetic joint infections (PJI) occur infrequently, but they represent the most devastating complication with high morbidity and substantial cost. Staphylococcus aureus are the most common infecting agents associated with acute PJI, and also appear in some cases of delayed PJI¹. S. aureus biofilm development can be divided in two stages: adhesion and proliferation². To avoid PJI bacterial adhesion has to be decreased.

Hybrid organo-inorganic sol-gel coatings are proposed as a promising biomaterial improvement³. One of these compounds is a mixture of two organopolisiloxanes: 3-methacryloxypropyltrimethoxysilane (MAPTMS) and tetramethylorthosilicate (TMOS). The aim of this work was to evaluate bacterial adhesion on MAPTMS-TMOS coating compared to titanium parts made by powder metallurgy.

MAPTMS-TMOS sol-gel coating was produced using a molar ratio of 1:2 (MAPTMS:TMOS) and dispersed in ethanol. The sol-gel was deposited by dip-coating on titanium parts made by powder metallurgy followed by a thermal treatment at 120 ºC for 30 minutes⁴. Titanium parts without sol-gel coating were used as control.

S. aureus 15981 strain adherence study was performed using the protocol described by Kinnari et al.⁵ with 90 min incubation. After incubation, the samples were stained with LIVE/DEAD BacLight Bacterial Viability Kit. Proportion of total adhered, live and dead bacteria was calculated and studied by using ImageJ software. The experiments were performed in triplicate.

The statistical data were analyzed by pairwise comparisons using the nonparametric Mann-Whitney test with a level of statistical significance of p<0.05. Values are cited and represented as medians.

S. aureus 15981 adherence was 942-fold lower on MAPTMS-TMOS coating than on uncoated titanium.

According with our results, MAPTMS-TMOS sol-gel coating is a promising antiadherent surface for S. aureus. More studies are necessary in order to evaluate this property with other species and strains.

Development of antibacterial surfaces or coatings to prevent bacterial adhesion and hence colonization of implants and biofilm formation is an attractive option, in order to reduce the tremendous impact of implant-related infections associated with modern surgery. To overcome the lack of in vivo and clinical models, able to evaluate the performance of anti-adhesive coatings, we designed an in vitro experimental setting that allows to quantitatively evaluate the ability of a coating to reduce bacterial adhesion on a given surface; this model may efficiently serve as a surrogate endpoint to validate anti-adhesive medical devices and compounds. Here we report the results the evaluation of the anti-adhesive properties of a patented, fast-resorbable hydrogel coating, (“Defensive Antibacterial Coating”, DAC).

Sterile sandblasted titanium discs of approximately 5cm² surface area were used as substrates for bacterial adhesion. The gel was prepared as follows: syringes prefilled with 300 mg of DAC powder (Novagenit Srl) were reconstituted with 5 ml of sterile water to obtain a hydrogel with a DAC concentration of 6%. Two experiments were conducted. In the first, 200 mg of hydrogel were homogenously spread on the surface of titanium disc, with the spreading device provided by the manufacturer. Both coated and uncoated substrates (controls) were overlaid with a standardized inoculum (10⁸ CFU/ml) of a wild methicillin-resistant Staphylococcus aureus strain, previously isolated from a peri-prosthetic joint infection, for 15, 30, 60 and 120 minutes. Afterwards, non-adherent bacteria were removed by rinsing with sterile saline. The remaining adhered cells were seeded on agar plates for CFU count. In the second experiment, the discs were first inoculated with bacterial cells followed by a treatment with the hydrogel and bacterial count as described above. Ten discs were used for each condition and each time interval (total 160 discs).

The adhesion density of S. aureus on titanium discs pre-treated with DAC was significantly lower than that observed on untreated controls at each time point. In particular, the average number of adherent bacteria at 15, 30, 60 and 120 minutes of incubation, was respectively reduced by 86.8%, 80.4%, 74.6% and 66.7%, compared to controls (p<0.001). DAC treatment of discs with previously adhered S. aureus reduced bacterial adhesion, at 15, 30, 60 and 120 minutes of incubation, by, respectively, 84.0% (p<0.05), 72.8%, 72.3% and 64.3% (p<0.001), compared to untreated controls.

Our results shows that DAC, “Defensive Antibacterial Coating”, has anti-adhesive properties that allow to reduce bacterial adhesion on a sanded titanium surface by more than 80%, even in the presence of remarkably high bacterial loads (10⁸ CFU/ml), of multi-resistant bacteria (MRSA) and even in the case of previous contamination. Providing anti-adhesive properties to a surface with a fast-resorbable coating may be a safe option to protect inorganic and organic surfaces and biomaterials. Those observation could be the pre-requisite for its in vivo application.

Bone-regenerative and biocompatible materials are indicated for the regeneration of bone lost in periodontology and maxillofacial surgery. Bio-Oss is a natural bone mineral for bone grafting of bovine origin and the most common used in this kind of interventions¹. Sil-Oss is a new synthetic nanostructured monetite-based material that is reabsorbed at the same time that is replaced by new bone tissue ². Bacterial infection is one of the complications related to this kind of material. Streptococcus oralis is the most associated oral infecting pathogen to oral surgery³ and Staphylococcus aureus is the most common infecting pathogen to maxillofacial non-oral interventions⁴. Here we evaluated bacterial adherence of two of the most common infecting bacteria of this kind of biomaterial: S. oralis and S. aureus, on Bio-Oss and Sil-Oss.

S. oralis ATCC 9811 and S. aureus 15981 strains were used. Bacterial adherence was evaluated using the modified previously described protocol of Kinnari et al.⁵ that was adapted to our biomaterial. The quantification was performed by the drop plate method⁶. The statistical data were analyzed by pairwise comparisons using the nonparametric Mann-Whitney test with a level of statistical significance of p<0.05. Values are cited and represented as medians.

Bacterial adherence decreased significantly on Sil-Oss compared to Bio-Oss. S. oralis ATCC 9811 adherence was between 11 and 13-fold less on Sil-Oss compared to Bio-oss. In the case of S. aureus15981, the adherence was between 4 and 6-fold less on Sil-Oss compared to Bio-Oss.

Sil-Oss nanostructured monetite-based biomaterial could be considered as a promising biomaterial to be used for the regeneration of bone defects since the bacterial adherence on it is lower than on another currently used material.

In a new rabbit model of carbapenem-resistant Klebsiella pneumoniae knee-prosthesis infection, we studied the efficacy of colistin cement alone or in combination with systemic intramuscular (i.m.) injections of colistin.

Seven days after infection, surgical debridement and removal of the infected prostheses were performed, and rabbits were randomly assigned to one of four different treatment groups of twelve rabbits: prosthesis replacement by drug-free cement spacer (control) prosthesis replacement by colistin-loaded cement spacer (3 MUI of colistin/40 g of cement) (colistin local), prosthesis replacement by drug-free cement spacer and i.m. colistin (12 mg/kg of body weight, three time a day for 7 days), or colistin local + i.m.

We observed a statistically significant difference (p = 0.049) between the colistin local + systemic group and the control group in the criteria of number of rabbits with sterile bone under the total number of rabbits.

Combination of systemic and local colistin could be an interesting therapeutic option to cure carbapenem-resistant Klebsiella pneumoniae peri prosthetic joint infection.

Around 1% of total hip replacements are follow by prosthetic joint infection (PJI). There is uncertainty about best treatment method for PJI, and the most recent high quality systematic reviews in unselected patients indicates that re-infection rates following one-stage and two-stage revision arthroplasty are relatively similar. In the absence of evidence randomised controlled trials will help to identify the most clinically and cost-effective treatment for PJI. Before such trials are conducted, there is a need to establish reasons for current practice and to identify whether trials are feasible. This study aimed to deliver research that would inform trial design. Specifically, we aimed to characterise consultant orthopaedic surgeons' decisions about performing either one-stage or two-stage exchange arthroplasty for patients with PJI after hip replacement and to identify whether a randomised trial comparing one-stage with two-stage revision would be possible.

Semi-structured interviews were conducted with 12 consultant surgeons from 5 high-volume National Health Service (NHS) orthopaedic departments in the UK. Surgeons were sampled on the basis that they perform revision surgery for PJI after hip arthroplasty and final sample size was justified on the basis of thematic saturation. Surgeons were interviewed face-to-face (n=2) or via telephone (n=10). The interview study took place before design of a multicentre prospective randomised controlled trial comparing patient and clinical outcomes after one-stage or two-stage revision arthroplasty. Data were audio-recorded, transcribed, anonymised and analysed using a thematic approach, with 25% of transcripts independently double-coded.

Results: There is no standard surgical response to the treatment of PJI and surgeons manage a complex balance of factors when choosing a surgical strategy. These include multiple patient-related factors, their own knowledge and expertise, available infrastructure and the infecting organism. Surgeons questioned whether evidence supports the emergence of two-stage revision as a method. They described the use of loosely cemented articulating spacers as a way of managing uncertainty about best treatment method. All surgeons were supportive of a randomised trial to compare one-stage and two-stage revision surgery for PJI after hip replacement. Surgeons reported that they would put patients forward for randomisation when there was uncertainty about best treatment.

Surgeons highlighted the need for evidence to support their choice of revision. Some surgeons now use revision methods that can better address both clinical outcomes and patients' quality of life, such as loosely cemented articulating spacers. Surgeons thought that a randomised controlled trial comparing one-stage and two-stage exchange joint replacement is needed and that randomisation would be feasible. The next stage of the work was to design a multi-centre randomised controlled trial, this has been achieved and the trial is now ongoing in the UK.

Around 1% of the 185,000 primary hip and knee arthroplasties performed in the UK are followed by prosthetic joint infection (PJI). Although PJI affects a small percentage of patients, it is one of the most devastating complications associated with this procedure. Treatment usually involves further major surgery which can adversely affect patients' quality of life. Understanding current service provision provides valuable information needed to design and evaluate support interventions for patients. The aim of this survey was to identify usual care pathways and support in UK NHS orthopaedic centres for this population.

The 20 highestvolume UK NHS orthopaedic centresfor hip and knee arthroplasty account for 33–50% of all cases treated for prosthetic joint infection. Infection leads at each centre were invited to participate in a survey about usual care provision and support for PJI. Questions exploredfollow up time-points; use of standard outcome measures; multidisciplinary care plans; supportive in-patient care and care after treatment; and onward referrals. Survey responses were recorded on a standardised proforma. Data were entered into Excel for analysis, then reviewed and coded into categories and frequency statistics to describe categorical data. A descriptive summary was developed based on these categories.

Eleven of the highestvolume orthopaedic centres completed the survey. Follow-up of patients varied greatly across centres; some centres reviewed patients at weekly or 2 week intervals, while all centres saw patients at 6 weeks. Long-term follow-up varied across centres from 3–4 monthsto 12 monthly. Length of follow-up period varied from until the infection had cleared toindefinitely. Follow-up timepoints were only standardised in 4 out of 11 centres. Only 1 centre had a dedicated infection clinic. Advice on who patients should contact if they had concerns included the consultant, community nurse, extended scope practitioner or the ward, while 3 centres told patients to avoid calling their GP. Only half of the centres routinely used standardised outcome measures with patients with PJI. The majority of centres provided standard physiotherapy and occupational therapy (OT) to in-patients while approximately half also offered social support. Only one centre provided dedicated physiotherapy and OT on a separate infection ward. Three centres provided hospital at home or community services to patients in-between operative stages. Only 3 out of 11 centres stated they had specific multidisciplinary care plans in place for patients. Once discharged most patients were provided with physiotherapy, OT and social services if needed. Common barriersto referral included complexities of referring patients outside the hospital catchment area;lack of availability of community services, and shortage of staff including physiotherapists. Delays in rehab and social services could also be problematic.

Findings show wide variation intreatment pathways and support for patients treated for PJI, both as inpatients and in the community. Only one of the 11 centreswho participated had a dedicated infection clinic. Only one centre suggested they individualised their physiotherapy support. A number of barriers exist to referring patients on to other support services after revision surgery.

Joint arthroplasty is a common surgical procedure, with over 185,000 primary hip and knee arthroplasties performed in England, Wales and Northern Ireland in 2014. After total hip or knee arthroplasty, about 1% of patients develop deep prosthetic joint infection (PJI), which usually requires further major operations to clear the infection. Although PJI affects only a small percentage of patients it is one of the most devastating complications associated with this procedure. Research evidence has focussed on clinical effectiveness of revision surgery while there has been less focus on the impact on patients and support needs. Using a systematic review approach, the aim of this study was to assess support needs and evaluate what interventions are routinely offered to support patients undergoing treatment for PJI following hip or knee arthroplasty.

We systematically searched MEDLINE, Embase, Web of Science, PsycINFO, Cinahl, Social Science Citation Index, and The Cochrane Library from 1980 to February 15, 2015 for observational (prospective cohort, nested case-control, case-control, and retrospective cohort) studies, qualitative studies, and clinical trials that report on the support needs and interventions for patients being treated for PJI or other major adverse occurrences following joint arthroplasty. Data were extracted by two independent investigators and consensus reached with involvement of a third.

Of 4,161 potentially relevant citations, we identified one case-control, one prospective cohort and two qualitative studies for inclusion in the synthesis. Patients report that PJI and treatment had a profoundly negative impact affecting physical, emotional, social and economic aspects of their lives. No study evaluated support interventions for PJI or other major adverse occurrences following hip and knee arthroplasty.

The interpretation of study results is limited by variation in study design, outcome measures and the small number of relevant eligible studies. Findings show that patients undergoing treatment for PJI have extensive physical, psychological, social and economic support needs. Our review highlights a lack of evidence about support strategies for patients undergoing treatment for PJI and other adverse occurrences. There is a need to design, implement and evaluate interventions to support these patients.

To prevent infections after orthopedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics. Bone allografts impregnated with antibiotics may therefore provide the necessary local antibiotic levels for prophylaxis. To be efficient, a prolonged release from these bonechips is required. In contrast to vancomycin, for which prolonged release has clearly been proven effective from Osteomycin®, a commercially available impregnated bone allograft, no prolonged release bone chip preparations have been described so far for cefazolin. We developed a protocol to bind cefazolin in the porous structure of bone chips by means of a hydrogel composed of proteins naturally present in the human body.

Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were either incubated for 20 min- 4h or also treated with vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analyzed by Ultra Performance Liquid Chromatography – Diode Array Detection.

Soaking of bone chips without hydrogel resulted in a quick release of cefazolin, which was limited to 4 hours. When vacuum was applied elution of >1 µg/ml cefazolin was measured for up to 36 hours. Combination with collagen hydrogel resulted in a higher cefazolin concentration released at 24 hours (3.9 vs 0.3 µg/ml), but not in a prolonged release. However, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 µg/ml followed by a gradual decline reaching the minimal inhibitory concentration for S. aureus at 72 hours (1.7 µg/ml), while not measurable anymore after 92 hours.

Processed bone chips with hydrogel-cefazolin showed a markedly prolonged cefazolin release. When combined with a fibrin hydrogel, high initial peak levels of cefazolin were obtained, followed by a decreasing release over the following three days. This elution profile is desirable, since high initial levels are important to maximize anti-bacterial action whereas low levels of antibiotic for a limited time may stimulate osteogenesis. It is important that antibiotic release is ending after a few days as prolonged low levels of antibiotics are not clinically helpful and may lead to antibiotic resistance. Further preclinical studies are warranted to show effectiveness of hydrogel-cefazolin impregnated bone chips.

Bone infection occurring after fractures or orthopedic surgery can progress to the chronic stage and lead to poor results of treatment. Optimal treatment of chronic osteomyelitis are stabilization the fracture, biological recovery of bone defects and destroy bacterial infection. Traditional methods of treatment are systemic administration of antibiotics and surgical treatment of active infection focus. Systemic antibiotics are part of the standard therapy after surgical treatment of infected bone, but their effectiveness is limited due to malnutrition and low absorption at the site of infection. Moreover, long-term treatment and higher doses are associated with serious side effects. The aim of this investigation was to study the results of the complex treatment of patients with chronic osteomyelitis using biodegradable nanomaterials “PerOssal” as antibiotic delivery system.

The study was performed at Regional center traumatology and orthopedics, Karaganda, Kazakhstan. A total 20 patient with post-traumatic/post-operative osteomyelitis were included in this open-label, prospective study. Bacteriological examination was taken with the determination of culture and sensitivity test preoperatively, during and postoperatively. After radical surgical debridement and ultrasound cavitation, the bone cavity was full filled with Perosal which can be loaded with different antibiotics depending from the antibiotic sensitivity test. Postoperative wound is completely was sutured. Systemic antibiotic treatment are allowed. The course of infection was monitored by determination leukocyte count and blood sedimentation rate; blood samples were taken befor, 24 hours after surgery, and on days 3, 7, 10, 14. Wound healing was assessed on days 2, 3, 7, 10, and at the time of removal of sutures. Resorption of implanted beads and bone reconstruction were evaluated by X-ray at after operation and at approximately one, three and six months after implantation.

A total of 20 patients (mean age 38,1 (26 to 53), 14 male, 6 female) were treated with Perossal pellets (AAP, Germany) from October 2013 to April 2015. Mean leukocyte counts and blood sedimentation rate were within the normal laboratory range and did not indicate infectious complications during the first 21 days after surgery. Primary wound healing occurred in 18 patients and secondary wound healing in two patients. There were two cases of re-infection during the course of the study, one of them related to an incomplete eradication of infected tissue and multidrug-resistant strain occurring during the course of the study, the other is occurred that patient non-compliance. Radiographic analysis six months after surgery showed progressive resorption of the implanted pellets, but only 10 cases have decreasing size of defects on X-ray.

This study in adult patients with chronic post-traumatic/post-operative osteomyelitis demonstrated that these biodegradable bone filler pellets which can be loaded with different antibiotics are a clinically useful local antibiotic delivery system and bone substitute which can be used as an alternative to other anti-infective implants. The implantation of the pellets was safety and well tolerated in all patients. This composite can provide adequate protection against bacterial infection during the first weeks after implantation and to support the bone healing process.

Infected wounds are a major problem for patients and health care systems. The inflammation triggers expression of high levels of extracellular protease activities which degrade newly formed granulation tissue. The expression of host-derived proteases had been studied in wound healing extensively. In contrast, the contribution of bacterial proteases in impaired healing acute and chronic wounds is poorly understood as is how bacterial proteases can be blocked.

In this study the expression of P. aeruginosa proteases was studied. P. aeruginosa is associated with poor healing and sufficiently common in wound infections to merit closer study. We used in vitro biofilm and planktonic culture models to analyze the culture-dependent expression of different P. aeruginosa proteases and how protease modulating polymers can inhibit activities.

P. aeruginosa (PAO1, DSM 22644) was grown in LB_o medium (aerated planktonic cultures) or in a biofilm culture model (dialysis tubing on LB_o plates). The supernatant of planktonic or wash fluids from biofilm cultures were analyzed for protease activity.

Global extracellular protease activities increased in a time- and culture condition-dependent manner (for planktonic cultures 180 ng/ml trypsin equivalent 8h, 330 ng/ml 24h, 490 ng/ml 48h; biofilm cultures 190 ng/ml trypsin equivalent 8h, 420 ng/ml 24h, 170 ng/ml 48h). Enzyme zymography revealed in biofilm cultures predominant bands at 50 kD (8h, 24h, 48h), 90 kD (24h) and > 200 kD (8h, 24h, 48h). In planktonic cultures the pattern was different 50 kD (8h), 90 kD (8h, 24h, 48h), 130 kD (24h, 48h) and > 200 kD (8h, 24h). Two different polyacrylate superabsorbers could inhibit P. aeruginosa protease activities. Favor PAC 300 blocked protease activity by 60% and SXM 9170 by 35%.

These data demonstrate complex, culture-dependent expression of extracellular proteases in P. aeruginosa, a microorganism associated with poor wound healing outcomes. From a therapeutic perspective polyacrylate superabsorbers strongly inhibited global protease activities. In the next steps the protease expression pattern needs to be analyzed in P. aeruginosa wounds and correlated with healing progression.

Chronic osteomyelitis is historically treated in a two stage fashion with antibiotic-loaded polymethylmethacrylate (PMMA) as local antibacterial therapy. However, two-stage surgeries are associated with high morbidity, long hospitalization and high treatment costs. In recent years new biomaterials were developed that allow to change this treatment algorithm. S53P4 bioactive glass is such a novel biodegradable antibacterial bone graft substitute that enables a one-stage surgery in local treatment of chronic osteomyelitis. This study aimed to explore the eradication of infection and bone healing capacities of S53P4 bioactive glass in clinical practice.

In this prospective longitudinal outcome study, clinical applicability of S53P4 bioactive glass in treatment of patients with chronic osteomyelitis was assessed. All patients with clinically, haematologically and radiologically evident chronic osteomyelitis were included. All patients were treated with an extensive debridement surgery, S53P4 bioactive glass implantation and systemic antibiotic administration. Primary endpoint of this study is eradication of infection. During follow-up eradication was analysed based on clinical outcomes, blood samples (inflammatory parameters) and radiological outcomes. The secondary endpoint, bone healing, is assessed using conventional radiographic images of the treated region.

Between 2011 and 2016, 25 patients were included in this study, with a mean follow-up of 23 months (range 4 – 57). Hospital stay was short with a mean of 18 days (range 4 – 40) and patients required an average of 1,4 surgeries (range 1 – 4). The inflammatory parameter C-reactive protein (CRP) showed a normalization after a mean duration of 46 days (range 0 – 211). At the end of follow-up haematological and clinical outcomes showed eradication of infection in 24 (96%) of all patients. Radiologically none of all patients showed persisting signs of infection and bone healing was observed in 22 (88%) patients based on changes on conventional radiographic images. One patient had a persistent infection without any bone healing, this patient had an infected non-union prior to surgery. There were two other patients with an initial infected non-union fracture which was not consolidated at last follow-up, although they had successful infection treatment. Another patient had a femoral fracture after surgery that needed additional surgery which did not interfere with eradication of infection. Four (16%) of all patients had initial wound healing problems related to compromised skin and/or soft tissue prior to surgery.

Based on the results of our clinical experience, S53P4 bioactive glass can successfully be used in a one-stage procedure for treatment of chronic osteomyelitis. Eradication of infection was successful in almost all patients and so far no patients required a second surgery due to infection recurrence. Bone healing (incorporation of the bioactive glass) was seen in all patients except for the patients with an initial infected non-union fracture. As a consequence of these results, we changed our institutional protocol for treatment of chronic osteomyelitis to a one-stage approach instead of a two-step approach.

Mesenchymal stem cells (MSCs) are self-renewing, multipotent cells that could potentially be used to repair injured cartilage in diseases. The objetive was to analyze different sources of human MSCs to find a suitable alternative source for the isolation of MSCs with high chondrogenic potential.

Femoral bone marrow, adipose tissue from articular and subcutaneous locations (hip, knee, hand, ankle and elbow) were obtained from 35 patients who undewent different types of orthopedic surgery (21 women, mean age 69.83 ± 13.93 (range 38–91) years. Neoplasic and immunocompromised patients were refused. The Ethical Committee for Clinical Research of the Government of Aragón (CEICA) approved the study and all patients provided informed consent. Cells were conjugated wiith monoclonal antibodies. Cell fluorescence was evaluated by flow cytometry using a FACSCalibur flow cytometer and analysed using CellQuest software (Becton Dickinson). Chondrogenic differentiation of human MSCs from the various tissues at P1 and P3 was induced in a 30-day micropellet culture [Pittenger et al., 1999]. To evaluate the differentiation of cartilaginous pellet cultures, samples were fixed embedded in paraffin and cut into 5- υm-thick slices. The slices were treated with hematoxylin-eosin and safranin O (Sigma-Aldrich). Each sample was graded according to the Bern Histological Grading Scale [Grogan et al., 2006], which is a visual scale that incorporates three parameters indicative of cartilage quality: uniform and dark staining with safranin O, cell density or extent of matrix produced and cellular morphology (overall score 0–9). Stained sections were evaluated and graded by two different researchers under a BX41 dual viewer microscope or a Nikon TE2000-E inverted microscope with the NIS-Elements software. Statistics were calculated using bivariate analysis. Pearson's χ2 or Fisher's exact tests were used to compare the Bern Scores of various tissues. To evaluate the cell proliferation, surface marker expression and tissue type results, ANOVA or Kruskal-Wallis tests were used, depending on the data distribution. Results were considered to be significant when p was < 0.05.

MSCs from all tissues analysed had a fibroblastic morphology, but their rates of proliferation varied. Subcutaneous fat derived MSCs proliferated faster than bone marrow. MSCs from Hoffa fat, hip and knee subcutaneous proliferated slower than MSCs from elbow, ankle and hand subcutaneous. Flow cytometry: most of cells lacked expression of CD31, CD34, CD36, CD117 (c-kit), CD133/1 and HLA-DR. At same time 95% of cells expressed CD13, CD44, CD59, CD73, CD90, CD105, CD151 y CD166. Fenotype showed no differences in cells from different anatomic places. Cells from hip and knee subcutaneous showed a worst differentiation to hyaline cartilage. Hoffa fat cells showed high capacity in transforming to hyaline cartilage.

Cells from different anatomic places show different chondrogenic potential that has to be considered to choose the cells source.

The objective of this study was to evaluate the safety and the effect of platelet-rich plasma (PRP) intra-articular injections obtained from blood donors (homologous PRP) on elderly patients with early or moderate knee osteoarthritis (OA) who are not candidates for autologous PRP treatment.

A total of 60 symptomatic patients, aged 65–86 years, affected by hematologic disorders and early or moderate knee OA, were treated with 5 ml of homologous PRP intraarticular injections every 14 days for a total of three injections. Clinical evaluations before the treatment, and after 2 and 6 months were performed by International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS) and Equal Visual Analogue Scale (EQ VAS) scores. Adverse events and patient satisfaction were recorded.

No severe complications were noted during the treatment and the follow-up period. A statistically significant improvement from basal evaluation to the 2-month follow-up visit was observed, whereas a statistically significant worsening from the 2-month to the 6-month follow-up visit was showed. The overall worst results were observed in patients aged 80 years or over and in those affected by minor bone attrition. It was found that 90% of patients were satisfied at the 6-month evaluation.

Homologous PRP has an excellent safety profile but offers only a short-term clinical improvement in selected elderly patients with knee OA who are not candidates for autologous PRP treatment. Increasing age and developing degeneration result in a decreased potential for homologous PRP injection therapy. Further studies are needed to confirm these findings.

Used routinely in maxillofacial reconstructive surgery, the chondrocostal graft is also applied to hand surgery in traumatic or pathologic indications. The purpose of this overview was to analyze at long-term follow-up the radiological and histological evolution of this autograft, in hand and wrist surgery. We extrapolated this autograft technique to the elbow by using perichondrium.

Since 1992, 148 patients have undergone chondrocostal autograft: 116 osteoarthritis of the thumb carpometacarpal joint, 18 radioscaphoid arthritis, 6 articular malunions of the distal radius, 4 kienbock's disease, and 4 traumatic loss of cartilage of the proximal interphalangeal (PIP) joint. Perichondrium autografts were used in 3 patients with elbow osteoarthritis.

Magnetic Resonance Imaging (MRI) was performed in 19 patients with a mean follow-up of 68 months (4–159). Histological studies were performed on: i) perioperative chondrocostal grafts (n=3), ii) chondrocostal grafts explanted between 2 and 48 months after surgery (n=10), and iii) perioperative perichondrium grafts (n=2).

Whatever the indication, the reconstruction by a chondrocostal/ostochondrocostal or perichondrium graft yielded satisfactory clinical results at long-term follow-up. The main question was the viability of the graft.

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For rib cartilage grafting: The radiological study indicated the non-wear of the graft and a certain degree of ossification. The MRI and histology confirmed a very small degree of osseous metaplasia and graft viability. The biopsies showed neo-vascularization of the cartilage that had undergone morphological, constitutional and architectural changes. Comparison of these structural modifications with perioperative chondrocostal graft histology is in progress.

Despite the strong mechanical strain in the hand and wrist, chondrocostal graft is a biological arthroplasty that is trustworthy and secure over the long term, although it can cause infrequent complications inherent to this type of surgery. Despite the inevitable histological modification, the cartilage remains alive and is of satisfactory quality at long term follow-up and fulfills the requirements for interposition and reconstruction of an articular surface.

The perichondrium graft constitutes a new arsenal to cure cartilage resurfacing. The importance of perichondrium for the survival of the grafted cartilage, as previously reported, as well as its role in resurfacing, is being investigated.

Due to its avascular nature, articular cartilage exhibits a very limited capacity to regenerate and to repair. Although much of the engineered cartilage grafts so far proposed have successfully shown to mimic the morphological and biochemical appearance of hyaline cartilage, they are generally mechanically inferior to the natural tissue¹. In this study a new bioreactor device was realized to test innovative scaffolds under physiological stimulation (i.e. perfusion fluid flow and dynamic compression), with the aim to produce a more functional engineered tissue construct for articular applications.

The computer-controlled bioreactor system has been properly designed to simultaneously provide static or dynamic compression and/or continuous perfusion to 3D engineered constructs, reproducing the physiological loads to which the articular cartilage is subjected. The specifically designed bioreactor comprises a chamber where the grafts are accommodated, a porous piston connected to a linear stepper motor (Dings, Model 34-2080-4-300), which controls its movement to provide mechanical stimulation and a peristaltic pump (Watson-Marlow, Model 323S), connected by joints and pipes to the culture chamber to ensure a continuous media perfusion. As piston for compression, a sintered stainless steel filter (43% of porosity) was adopted to allow the perfusion of the culture media during physical stimulation. The culture chamber is composed by a hollow cylinder (30 mm × 40,5 mm) and a base realized as a single object. They are made in polycarbonate for its characteristics of transparency and infrangibility and linked to a Nylon cover through four brass tie rods unscrewable from above. The chamber has been designed to accommodate simultaneously different constructs of any size and shape and stimulate them with perfusion and/or dynamic compression. A finites elements program was used to mimic the effects of perfusion and compression regime on the scaffolds cultured within the bioreactor chamber.

The bioreactor was properly designed and developed. Particular attention has been paid to the implementation of a simple, compact and economical system. It was then tested by using different polymeric porous scaffolds (PVA, collagen, Gelatin grafts, both porous and not) cultured with mesenchymal cells up to two weeks. The system has been validated in terms of sterility, experimental reproducibility and ease to use. The structural stability of grafts over time has been observed; moreover cells adhesion, proliferation and matrix production under different chemical-physical stimuli conditions is under investigation.

We have realized a novel bioreactor system representing an artificial articular niche, where a dynamic compression combined with fluid perfusion allows to functionally and mechanically validate tissue substitutes, besides investigating the response of engineered cartilaginous tissues to physical stimuli mimicking the natural cartilage micro-environment. Such bioreactor may be in fact adopted as a sort of articular simulator for promoting and standardizing the new tissue formation in vitro, preconditioning cell fate through the application of proper artificial stimuli. Moreover, they can be valid tools to investigate physiological processes and novel therapeutic approaches avoiding controversial animal models.

The femur is a common site for skeletal bony metastases. The aim of this study is to evaluate the outcomes of femoral intramedullary nailing in prophylactic versus therapeutic treatment in femoral metastases.

All femoral nails between April 2011 and November 2015 at a district general hospital were assessed. Intramedullary nailing performed for prophylactic or therapeutic management were included. Outcomes include mortality, survival time and length of stay in hospital.

A total of 40 cases were included. In the prophylactic group there were 25 patients and in the therapeutic group there were 15 patients. In the prophylactic group, mean age was 70 years (range 41–91); male to female ratio is 23:17 and 26 patients of this group was deceased. In the therapeutic group, mean age was 76 years (range 56–92); male to female ratio 15:10 and 10 patients were deceased in this group. The most common primary was prostate carcinoma followed by breast carcinoma. In the prophylactic group, mean survival was 25 weeks (range 2–147) and in the therapeutic group mean survival was 20 weeks (range 2–39). The length of stay was 21 days (range 3–80) in the prophylactic group and 28 days (range 7–63) in the therapeutic group.

Femoral nailing for metastases helps improve quality of life and we observed a mean survival time of 20–25 weeks postoperatively in both therapeutic and prophylactic nailing.

Osteosarcoma (OS) is an aggressive bone malignancy with a high relapse rate despite combined treatment with surgery and multiagent chemotherapy. As for other cancers, OS-associated microenvironment may contribute to tumor initiation, growth, and metastasis. We consider mesenchymal stromal cells (MSC) as a relevant cellular component of OS microenvironment, and have previously found that the interaction between MSC and tumor cells is bidirectional: tumor cells can modulate their peripheral environment that in turn becomes more favourable to tumor growth through metabolic reprogramming (1).

Stem-like cells were derived from HOS osteosarcoma cell line by using the spherogenic system (2). CSC isolated from HOS (HOS-CSC) were co-coltured with MSC isolated from bone marrow. Cell lysates and supernatants were collected for the analysis of RNA expression and of secreted cytokines, by Q-RT-PCR and specific ELISA assays, respectively.

Here, we determined the effects of MSC on OS stemness and migration, two major features associated with recurrence and chemoresistance. Recruitment of MSC to the tumor environment leads to enhanced proliferation of OS stem cells, which increase the expression levels of TGFβ1. The latter, in turn, could be responsible for the activation of NF-kB genes and IL-6 secretion by MSC. Pro-tumorigenic effects of MSC, via IL-6, including induction of HOS-CSC migration and sphere growth, can be counteracted by IL-6 neutralizing antibody. The presence of MSC is also responsible for increased expression of adhesion molecules involved in intra- or extra-vasation.

Stromal cells in combination with OS spheres exploit a vicious cycle where the presence of CSC stimulates mesenchymal cytokine secretion, which in turn increases stemness, proliferation, migration, and metastatic potential of CSC. Furthermore, for the first time we identified a novel OS stem cell marker, the Met proto-oncogene, that is frequently overexpressed and is pathogenetically relevant in OS (2 and 3). Altogether, our data corroborates the concept that a comprehensive knowledge of the interplay between tumor and stroma that also includes the stem-like fraction of tumor cells is needed to develop novel and effective anti-cancer therapies.

Osteosarcoma (OS) is a highly malignant primary tumor frequently occurring in children and adolescents. The mainstay of therapy is neoadjuvant chemotherapy and surgical removal of the lesion yielding a 50–70% of 5-year survival rate. Unfortunately, chemotherapy is currently unable to induce complete tumor necrosis leaving residual tumor cells free to metastasize or recidivate, thus resulting in a 30% mortality. The major limitation in those patients is the development of multidrug resistance (MDR) and the low water solubility of drugs such as Paclitaxel (PTX) that is in fact not included in the majority of chemotherapy protocols for OS treatment.

We thus hypothesized to prevent the emergence of MDR and obtain significant tumor reduction, by engineering innovative nanoparticles (NPs) able to vehiculate the PTX and induce a dual synergic action: the cytostatic effect of PTX and the cytotoxicity generated by reactive oxygen species produced from light triggered photoactivation (PDT) of Chlorin e6 photosensitizer. To further improve the efficacy and reduce the side effects of NPs systemic administration, Mesenchymal Stromal Cells (MSC) are used as a “Trojan horse” to deliver the NPs directly to tumor cells, taking advantage of MSC ability to selectively recognize and efficiently engraft in OS tumor stroma.

HSA were conjugated with photosensitizer Ce6 and the functionalized protein was used to produce PTX loaded nanoparticles through desolvation technique and drug-induced protein self-assembly (PTX-Ce6@HSA NP).

Human MSC lines, isolated from the Bone marrow (BM) of different donors, were then loaded with different dosages of nanoparticles and their ability to internalize and transport the NPs, migrate and induce cytotoxic ROS upon light treatment were tested in in vitro cultures.

Preliminary results showed that MSC efficiently internalize PTX-Ce6@HSA NPs and the photosensitizer Ce6 remains active inside the cells for at least 3 days after loading.

Electron microscopy performed onto loaded MSC showed that NPs internalization take places via clathrin mediated transport, whereas HPLC analysis demonstrated a release kinetics of PTX mediated by exocytosis. Finally, PTX-Ce6@HSA NPs loaded MSC co-cultured with the OS tumor cell line SaOS-2 showed a significant tumor cell growth reduction.

So fare, advances in drug delivery have failed to produce specific tool to improve the overall survival of OS patients. However, given our preliminary in vitro data we believe that the proposed multimodal therapy will minimize the side effects of the systemic chemotherapy and enhance the efficacy through the synergic effect of PTX and PDT.

In the future, our strategy could be intended as an innovative co-adjuvant approach for OS treatment to be performed right before surgery to eliminate residual tumors cells after tumor mass removal.

The nature of the Aneurysmal Bone Cyst (ABC) is still controversial among benign tumor, often identifiable in the “aggressive” form (Enneking stage 3) or pseudotumoral lesion. It is well known instead the very high risk of intraoperative bleeding, indicating a strongly unfavorable relationship between the surgical morbidity and the nature of the disease. Recently, excellent results have been obtained in the treatment of ABC by repeated arterial embolizations (SAE), without any surgery, while initial experiences with administration of denosumab and doxycycline are still under study. This study presents the results of our initial experience in the treatment of vertebral ABC through the use of concentrated autologous mesenchymal stem cells (MSCs).

Two teenagers aged 15 years, male, and 14 years, female, came to our attention both with diagnosis of ABC in C2 vertebra which was histologically confirmed. They were both neurologically intact, the girl complained of neck pain. The arteriography showed in both cases close relationships between the pathological ABC vascularization and the vertebral and cervical ascending arteries, making treatment by selective arterial embolization unsuitable. After discussion with the parents of patients, we jointly decided to undertake the treatment by direct injection of MSCs preceded, in the same operative session, by harvesting from the iliac crest of 60 cc of bone marrow (by needle aspiration) and its separation with the use of concentration system Res-Q ™ 60 BMC. In the second case the treatment was repeated two times at distance of 4 months.

The clinical and radiological follow-up is to of 30 months from the first treatment in both cases. In the first case the presence of newly formed bone within the ABC appeared as a clear sign of recovery just a month after the first treatment and increased gradually, until the cyst appeared completely ossified one year after the treatment, with associated disappearance of the pain. In the second case an initial sclerotic peripheral margin appeared after the second treatment and later ossification progressed, concurrently with the disappearance of the pain.

Treatment with selective serial arterial embolization is considered effective in the treatment of ABC even if not without risks, mainly related to the frequent and repeated exposure to ionizing radiation. Furthermore, in a certain percentage of cases the procedure is not technically executable, especially for the presence of arteries afferent to the medullar vascularization. Inconsistent results were obtained with other procedures: the injection of calcitonin, steroid, alcoholic solutions, or the use of sclerosing substances. Radiation therapy, though very effective, it is not considered the first choice. Recently, promising results have been achieved by the injection of mononuclear cells derived from bone marrow in the treatment of Aneurysmal Bone Cyst. Based on the early results obtained in the two cases described, the injection of MSCs can be considered a valid alternative in the treatment of vertebral ABCs untreatable by embolization.

Dysplasia Epiphysealis Hemimelica (DEH) also known as Trevor's Disease is a rare developmental disorder resulting in cartilaginous overgrowth of the epiphysis of long bones. DEH is usually diagnosed in children between two and eight years old and it is three times more often diagnosed in boys. The most reported complaints are pain, limitation in range of motion, and deformity or swelling of the affected joint. Treatment of symptomatic lesions consists of surgical resection of the lesion, resulting in good long-term results.

Based on histological evaluation, DEH is often described as an osteochondroma or an osteochondroma-like lesion, although there are clinical, radiological and genetic differences between DEH and osteochondromas. To investigate the hypothesis that DEH and osteochondromas are histologically identical, two cases of DEH and two cases of osteochondromas in patients with Hereditary Multiple Osteochondroma (HMO) are compared at histological level.

Tissue samples from patients with a histopathologically confirmed diagnosis of DEH were compared with two age and gender matched patients diagnosed with HMO. After tissue sampling and processing, (immuno)histological stainings were performed for Collagen type II, Collagen type X, Sox-9 and Safranin-O.

Histologically, clumping of chondrocytes in a fibrillar matrix, a thick disorganized cartilage cap and ossification centres with small amounts of unresorbed cartilage were observed in DEH. In contrast, chondrocyte organisation in cartilage of osteochondromas displays characteristics of the normal growth plate. In addition, differences in expression of collagen type II, collagen type X and Sox9 were observed. Collagen type II was expressed in the extracellular matrix surrounding proliferative and hypertrophic chondrocytes in osteochondromas, while weak expression was observed in the entire cartilage cap in DEH. Collagen type X was not expressed in DEH, while expressed in the pericellular matrix surrounding hypertrophic chondrocytes in osteochondromas. Staining for Sox9 was positive in the hypertrophic chondrocytes in osteochondromas, while expressed in the nuclei of all chondrocyte clusters in DEH.

Both morphological and immunohistological differences were observed in histological sections of DEH and osteochondromas. These findings reject our hypothesis, and supports the earlier observed clinical, radiological and genetic differences and implies a different aetiology between DEH and osteochondroma formation in HMO.

The function of the knee joint is to allow for locomotion and is comprised of various bodily structures including the four major ligaments; medial collateral ligament (MCL), lateral collateral ligament (LCL), anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL). The primary function of the ligaments are to provide stability to the joint. The knee is prone to injury as a result of osteoarthritis as well as ligamentous and meniscal lesions. Furthermore, compromised joint integrity due to ligamentous injury may be a result of direct and indirect trauma, illness, occupational hazard as well as lifestyle. A device capable of non-invasively determining the condition of the ligaments in the knee joint would be a useful tool to assist the clinician in making a more informed diagnosis and prognosis of the injury. Furthermore, the device would potentially reduce the probability of a misdiagnosis, timely diagnosis and avoidable surgeries.

The existing Laxmeter prototype (UK IPN: GB2520046) is a Stress Radiography Device currently limited to measuring the laxity of the MCL and LCL at multiple fixed degrees of knee flexion. Laxity refers to the measure of a ligament's elasticity and stiffness i.e. the condition of the ligament, by applying a known load (200N) to various aspects of the proximal tibial and thereby inducing tibial translation. The extent of translation would indicate the condition of the ligament. The Laxmeter does not feature a load applying component as of yet, however, it allows for the patient to be in the most comfortable and ideal position during radiographic laxity measurement testing. The entire structure is radiolucent and attempts to address the limitations of existing laxity measurement devices, which includes: excessive radiation exposure to the radiographic assistant, little consideration for patient ergonomics and restrictions to cruciate or collateral ligament laxity measurements.

The study focusses on further developing and modifying the Laxmeter to allow for: the laxity measurement of all four major ligaments of the knee joint, foldability for improved storage and increased structural integrity. Additionally, a load applicator has been designed as an add-on to the system thereby making the Laxmeter a complete Stress Radiography Device. Various materials including Nylon, Polycarbonate, Ultra High Molecular Weight Polyethylene (UHMWPE) – PE 1000, and Acetal/ POM were tested, using the Low Dose X-ray (Lodox) scanner, to determine their radiolucency. All materials were found to be radiolucent enough for the manufacture of the Laxmeter structure as well as the load applicator in order to identify and measure the translation of the tibia with respect to the stationary femur.

The Laxmeter allows for the measurement of the laxity of the MCL and LCL at multiple fixed degrees of flexion by providing the ideal patient position for testing. The next iteration of the device will present an affordable and complete Stress Radiography Device capable of measuring the laxity of all four major ligaments of the knee joint at multiple fixed degrees of flexion. Future work would include aesthetic considerations as well as an investigation into carbon-fibre-reinforced plastics.

Non-invasive, in vivo measurement of the three-dimensional (3-D) motion of the tibiofemoral joint is essential for the study of the biomechanics and functional assessment of the knee. Real-time magnetic resonance imaging (MRI) techniques enable the measurement of dynamic motions of the knee with satisfactory image quality and free of radiation exposures but are limited to planar motions in selected slice(s). The aims of the current study were to propose a slice-to-volume registration (SVR) method in conjunction with dual-slice, real-time MRI for measuring 3-D tibiofemoral motion; and to evaluate its repeatability during passive knee flexion.

Eight healthy young adults participated in the current study, giving informed written consent as approved by the Institutional Research Board. A 3-T MRI system (Verio, Siemens, Erlangen, Germany) incorporated with a neck matrix coil was used to collect the MRI data. A 3-D scanning using the VIBE sequence was used to collect the volumetric data of the knee at fully extended position (TR = 4.64 ms, TE = 2.3 ms, flip angle = 15°, in-plane resolution = 0.39 × 0.39 mm² and slice thickness = 0.8 mm). A real-time MRI using the refocused radial FLASH sequence (TR = 4.3 ms, TE = 2.3 ms, flip angle = 20°, in-plane resolution = 1.0 × 1.0 mm², slice thickness = 6 mm) was used to acquire a pair of image slices of the knee at a frame rate of 3 fps during passive flexion.

The volumetric MRI data sets were segmented for the femur and tibia/fibula to isolate the sub-volumes containing bone segments. A slice-to-volume registration method was then performed to determine the 3-D poses of the bones based on the spatial matching between sub-volume of the bones and the real-time image slices. The bone poses for all frames were used to calculate the rigid-body kinematics of the tibiofemoral joint in terms of the flexion/extension (FE), internal/external rotation (IR/ER), abduction/adduction (Abd/Add) and joint center translations along three anatomical axis of the tibia. The procedures were carried out five times for repeatability analysis. The standard deviation (SD) of the rigid-body kinematics for each frame from the five trials were calculated and then averaged across all frames to give quantitative measures of the repeatability of the kinematic variables.

The repeatability analysis showed that the mean±SD of the averaged SD in FE, Abd/Add and IR/ER components across all subjects were 0.25±0.09, 0.46±0.13 and 0.77±0.16 degrees, respectively. The corresponding values for the joint translations in anterior/posterior, proximal/distal and medial/lateral directions were 0.21±0.04, 0.11±0.03 and 0.43±0.09 mm.

An SVR method in conjunction with dual-slice real-time MRI has been successfully developed and its repeatability in measuring 3-D motion of the tibiofemoral joint evaluated. The results show that the proposed method is capable of providing rigid-body kinematics with sub-millimeter and sub-degree precision (repeatability). The proposed SVR method using real-time MRI will be a valuable tool for non-invasive, functional assessment of the knee without involving ionizing radiation, and may be further developed for joint stability assessment.

Total Hip Replacement (THR) is one of the most successful operations in all of medicine, however surgeons just rely on their experience and expertise when choosing between cemented or cementless stem, without having any quantitative guidelines. The aim of this project is to provide clinicians with some tools to support in their decision making. A novel method based on bone mineral density (BMD) measurements and assessments was developed 1) to estimate the periprosthetic fracture risk (FR) while press-fitting cementless stem; 2) to evaluate post-operative bone remodeling in terms of BMD changes after primary THR.

Data for 5 out of over 70 patients (already involved in a previous study¹) that underwent primary THA in Iceland were selected for developing novel methods to assess intra-operative FR and bone mineral density (BMD) changes after the operation. For each patient three CT images were acquired (Philips Brilliance 64 Spiral-CT, 120 kVp, slice thickness: 1 mm, slice increment: 0.5 mm): pre-op, 24 hours and 1 year post-operative.

Pre-op CT scan was used to create 3D finite element model (Materialise Mimics) of the proximal femur.

The material properties were assigned based on Hounsfield Units. Different strategies were analyzed for simulating the press-fitting operation, developing what has already been done in prior study¹. In the finite element simulation (Ansys Workbench), a pressure (related to the implant hammering force of 9.25 kN²) was applied around the femur's hollow for the stem and the distribution of maximum principal elastic strain over the bone was calculated. Assuming a critical failure value³ of 7300 με, the percentage of fractured elements was calculated (i.e. FR).

Post 24 hours and Post 1 year CT images were co-registrated and compared (Materialise Mimics) in order to assess BMD changes. Successively, volumes of bone lost and bone gained were calculated and represented in a 3D model.

Age and gender should not be taken as unique indicators to choose between implants typologies, since also three dimensional BMD distribution along with volume of cortical bone influence the risk of periprosthetic fractures. Highest FR values were experienced in the calcar-femorale zone and in similar location on the posterior side.

BMD loss volume fractions after 1 year were usually higher than BMD gain ones. Consistently with prior studies⁴, BMD loss was mainly concentrated around the proximal end (lesser trochanter area, outer bone).

If present, BMD gain occurred at the distal end (below stem's tip) or proximally (lesser trochanter area, interface contact with the stem).

The use of clinical data for BMD assessments serves as an important tool to develop a quantitative method which will support surgeons in their decisions, guiding them to the optimal implant for the patient. Knowing the risk of fracture if choosing a cementless stem and being aware of how the bone will remodel around the stem in one year's time can eventually lead to reduction in revisions and increased quality of life for the patient. Further work will target analysis of a larger cohort of patients and validate FE models.

Cancer associated bone pain (CIBP) is a common event in patients with advanced disease with bone metastases (BM), significantly impairing their quality of life. Treatment options are limited and mainly based on the use of opioids with unacceptable side effects. Local acidosis is a well-known cause of pain since it directly stimulates nociceptors that express acid-sensing ion channels and densely innervate bone. In BM, local acidosis derives from osteoclast bone resorption activity and from the acidification by glycolytic tumor cells. Here we speculated that the pH lowering of intratumoral interstitial fluid also promotes nociceptors sensitization and hyperalgesia through the activation of cells of mesenchymal origin in BM microenvironment that might release inflammatory and nociceptive mediators.

As a model of breast cancer that can metastatise to the bone we used MDA-MB-231 (MDA), and a subclone with a higher tendency to form osteolytic BM (bmMDA). We evaluated the basal expression of proton pumps/ion transporters by Real-Time PCR (Q-RT-PCR). To evaluate the effect of extracellular acidosis on mesenchymal tumor-associated stroma, we used human osteoblast primary cultures from healthy donors and cancer-associated fibroblasts isolated with specific immunobeads from the tumor biopsies of patient with BM. We exposed the cells to pH 6.8 medium at different time points (between 3 to 24 hours). After the short-term incubation with acidosis, for the expression of and acid-sensing ion channels, inflammatory cytokines and nociceptive mediators that can produce hyperalgesia, we used both a wide screening through a deep-sequencing approach and Q-RT-PCR, and ELISA. Xenograft for osteolytic BM induced by intratibial injection of bmMDA were treated with Omeprazole and monitored for CIBP through several cognitive tests.

We found a significantly higher extracellular proton efflux and expression of proton pumps/ion transporters associated with the acid-base balance, the monocarboxylate transporter 4 (MCT4), the carbonic anhydrase (CA9), and the vacuolar ATPase (V-ATPase) V₁G₁ subunit, and V₀c subunitin bmMDA, a subclone that is prone to form BM in respect to the parental cell line MDA-MB-231. In mesenchymal stromal cells, osteoblasts and cancer-associated fibroblasts, the incubation with pH 6.8 induced the expression of the achid-sensing ion channels AISC3/ACCN3 and AICS4/ACCN4, as well as of the nociceptive modulators nerve growth factor (NGF), Brain-derived neurotrophic factor (BDNF), and of the inflammatory cytokines interleukin 6 (IL6) and 8 (IL8), and Chemokine (C-C motif) ligand 5 (CCL5). Furthermore, the targeting of V0c subunit to inhibit intratumoral acidification significantly reduced CIBP in mice model of BM.

In this study we demonstrated for the first time that, in addition to the direct acid-sensing neuronal stimulation, the acidic microenvironment of BM causes hyperalgesia through the activation of an inflammatory reaction in the tumor-associated mesenchymal stroma at the tumor site, thereby offering as a new target for palliative treatment in advanced cancer.

The postoperative course of median nerve decompression in the carpal tunnel syndrome may sometimes be complicated by postoperative pain, paresthesias, and other unpleasant symptoms, or be characterized by a slow recovery of nerve function due to prolonged preoperative injury causing extensive nerve damage.

The aim of this study is to explore any possible effects of alpha lipoic acid (ALA) in the postoperative period after surgical decompression of the median nerve at the wrist.

Patients were enrolled with proven carpal tunnel syndrome and randomly assigned into one of two groups: Group A: surgical decompression of the median nerve followed by ALA for 40 days. Group P: surgical decompression followed by placebo. The primary endpoint of the study was nerve conduction velocity at 3 months post surgery, Other endpoints were static 2 point discrimination, the Boston score for hand function, pillar pain and use of pain killers beyond the second postoperative day.

ALA did not show to significantly improve nerve conduction velocity or Boston score. However, a statistically significant reduction in the postoperative incidence of pillar pain was noted in Group A. In addition, static 2 point discrimination showed to be significantly improved by ALA.

Administration of ALA following decompression of the median nerve for carpal tunnel release is effective on nerve recovery, although this is not detectable through nerve conduction studies but in terms of accelerated and improved static two-point discrimination.

The use of ALA as a supplementation for nerve recovery after surgical decompression may be extended to all types of compression syndromes or conditions where a nerve is freed from a mechanical insult.

Furthermore, ALA limits post-decompression pain, including late pericicatricial pain at the base of the palm, the so called pillar pain, which seems to be associated with a reversible damage to the superfical sensitive small nerve fibers.

In conclusion postoperative administration of ALA for 40 days post-median nerve decompression was positively associated with nerve recovery, induced a lower incidence of postoperative pillar pain and was associated with a more rapid improvement of static two-point discrimination. This treatment is well tolerated and associated with high levels of satisfaction and compliance, supporting its value as a standard postoperative supplementation after carpal tunnel decompression.

The goals of perioperative management are to relieve pain, achieve early mobilization after surgery, reduce length of hospital stay, and obtain adequate patient satisfaction. Several treatment options combining systemic analgesics and/or regional analgesia with or without opioids are available for postoperative pain; however, a gold standard has not been established although there is a progressive shift towards multimodal approaches to improve analgesia while minimizing opioid-related side effects.

EX-TRA-05 (DAVID-ART) was a randomised, double-blind, parallel, pivotal study, evaluating the analgesic efficacy and safety of the innovative oral combination of dexketoprofen/tramadol 25mg/75mg in comparison with the individual components (tramadol given at the higher dose of 100mg) on moderate to severe acute pain after total hip replacement. Repeated doses of study drug were administered every 8 hours and pain intensity (PI) was to be scored according to a 100mm visual analogue scale (VAS) on a programmed e-diary every 2 hours over a 56-hour period (i.e. along 7 repeated doses). A placebo arm was included at the first administration to validate the pain model. Rescue medication, metamizole 500mg, was available during the treatment period. The study primary endpoint was the mean sum of the pain intensity difference values throughout the first 8 hours (SPID₈), which considered the 3 active treatment arms and placebo (ITT population; N=641). In this phase, a clear superiority of the combination over the single agents was demonstrated (p<0.05). An additional analysis was performed during the entire 0–56h repeated-dose period excluding those patients who had received placebo at the first dose (N=161). The estimated mean (SE) differences on PI-VAS over 24, 32 and 56 hours post first dose (0–24h, 0–32h, and 0–56h) between the combination and each single agent were evaluated.

Patients who received active analgesic from the first dose (mITT population; N=480) were aged 29–80 years (42% were ≥65 years). At randomisation, pain was moderate (≥40–60mm) in 51% patients and severe (>60mm) in 49%. For dexketoprofen/tramadol, mean (SD) PI-VAS values were 22 (4.0) over 24 hours; 21 (4.1) over 32 hours; and 19 (3.8) over 56 hours. The estimated differences versus dexketoprofen 25mg and tramadol 100mg were respectively 10 (0.7) and 7.6 (0.7) over 24 hours; 9.8 (0.6) and 7.2 (0.6) over 32 hours; and 8.1 (0.5) and 6.3 (0.5) over 56 hours (p<0.0001 for all comparisons), which confirmed the superiority of the combination versus both single agents throughout the periods analysed.

This significant higher decrease of PI favouring dexketoprofen/tramadol 25mg/75mg over dexketoprofen 25mg and tramadol 100mg, all given every 8 hours, during the first 56 hours post dose confirmed the superior analgesia shown after the first 0–8h post-dose period. The combination of dexketoprofen/tramadol 25mg/75mg is able to provide a level of analgesia above that achievable by each component alone, with a sustained effect when used as a multiple-dose regimen. The addition of this new combo to the analgesic armamentarium may contribute to facilitate early mobilization after surgery, thus positively impacting perioperative co-morbidities and length of in-hospital stay.

Newer irreversible oral anticoagulants such as rivaroxaban, a direct factor 10a inhibitor, are increasingly employed to prevent thromboembolic events in atrial fibrillation (AF) patients, and to manage venous thromboembolism (VTE). Unlike warfarin, these agents require no monitoring and involve infrequent dose adjustment. We report the case of a patient treated with rivaroxaban for AF. Patient presented with unprovoked sudden onset right shoulder pain which clinically resembled shoulder haemarthrosis.

A single case was anonymised and retrospectively reviewed through examination of clinical and radiographic data.

A 70 year old female with known AF presented to Accident and Emergency with sudden onset of right shoulder pain and limited movement, which developed over one hour. The pain was constant, localised to the shoulder and without trauma. Past medical history included severe aortic regurgitation and associated thoracic aortic aneurysm, heart failure, atrial fibrillation and hypertension. Observations were normal upon admission with no haemodynamic compromise or pyrexia. Examining the right shoulder demonstrated distension of shoulder joint capsule, tenderness and a reduced range of movement. Temperature and neurovascular status in the right arm were normal. Investigations upon admission included an INR of 1.2. An anteroposterior right shoulder radiograph showed no evidence of fracture. Patient was managed conservatively with simple oral analgesia. Importantly, rivaroxaban was withheld for 5 days and symptoms resolved. Warfarin therapy was subsequently commenced instead as treatment for AF. Patient was discharged one week later and seen in clinic two weeks post-discharge. A full recovery occurred and with a full range of movement in the right shoulder.

In the UK, current National Institute for Health and Care Excellence (NICE) guidelines recommend the use of factor 10a inhibitors, for prevention of stroke in AF patients, and following elective total hip and knee replacement operations to prevent VTE. In turn, rivaroxaban is increasingly prescribed as first line therapy. Whereas warfarin has a documented association with haemarthrosis, there is no primary literature evaluating the incidence of factor 10a therapy associated haemarthrosis. In our case, the unprovoked shoulder haemarthrosis resolved following rivaroxaban cessation. In comparison with warfarin, rivaroxaban is irreversible. With warfarin and a high INR, vitamin K can be used to reverse the anticoagulation. There is no equivalent for rivaroxaban. We suggest further studies into incidence of haemarthrosis associated with oral anticoagulant therapy be undertaken, and treating physicians be aware of such complication.

Rehabilitation systems based on inertial measurement units (IMU) and bio-feedbacks are increasingly used in many different settings for patients with neurological disorders such as Parkinson disease or balance impairment, and more recently for functional recover after orthopedic surgical interventions or injuries especially concerning the lower limb. These systems claim to provide a more controlled and correct execution of the motion exercises to be performed within the rehabilitation programs, hopefully resulting in a better outcomes with respect to the traditional direct support of a physical therapists. In particular recruitment of specific muscles during the exercise is expression of its correct and finalized execution. The objective of this study was to compare muscular activation patterns of relevant lower limb muscles during different exercises performed with traditional rehabilitation and with a new validated system based on IMU and biofeedback (Riablo, Corehab, Trento, Italy).

Twelve healthy subjects (mean age 28.1 ± 3.9, BMI 21.8± 2.1) were evaluated in a rehabilitation center. Muscular activation pattern of gluteus maximum, gluteus medium, rectus femoris and biceps femoris was recorded through surface EMG (Cometa; Milan) during six different motion tasks: hip abduction in standing position, lunge, hip flexion with extended knee in standing position, lateral lunge, hip abduction with extended knee in lateral decubitus, squat. Subjects performed 10 repetitions of each task for a total of 100 repetitions per motion task, with and without Riablo System as well as during standard rehabilitation. An additional IMU was positioned on the shank in order to detect beginning and end of each repetition. A single threshold algorithm was used to identify muscle activation timing.

During hip abduction in standing position, gluteus maximum and rectus femoris showed a better and longer activation pattern while using Riablo compared to traditional rehabilitation. Gluteus medium showed a similar activation pattern whereas biceps femoris showed no activation from 30% to 80% using Riablo. During squat, rectus femoris and biceps femoris had a similar activation pattern with and without Riablo whereas gluteus maximum and gluteus medium showed a better activation pattern while using Riablo.

The recent development of innovative rehabilitation systems meets the need of manageable, reliable and efficient instruments able to reduce rehabilitation costs but with the same good clinical outcomes. Muscular activation patterns of relevant lower limb muscles during selected motion tasks reveal their correct execution. The use of this new rehabilitation system based on IMU and biofeedback seems to allow a more selective and effective muscular recruitment, likely due to the more correct and controlled execution of the exercise, particularly for the identification and interdiction of possible compensation mechanisms.

The superior analgesic effects of minodronate compared with other bisphosphonates has been previously reported. However, to our knowledge, there are no studies analyzing the analgesic effects of bisphosphonates on chronic pain. The purpose of the present study was to evaluate the analgesic effects of minodronate (MIN), alendronate (ALN), and pregabalin (PRG) on chronic pain caused by chronic constriction injury (CCI) of the sciatic nerve.

Four-week-old female Wister rats underwent ovariectomy. At 8 weeks old, the left sciatic nerve was ligated to induce the chronic pain model (CCI side), and sham surgery was performed on the right posterior limb as a CCI control (control side). The rats were divided into the following four groups: 1) MIN group, administered with minodronate (0.15 mg/kg/week) (n = 10); 2) ALN group, administered with alendronate (0.15 mg/kg/week) (n = 10); 3) PRG group, administered with pregabalin (10 mg/kg) (n = 9); and 4) Control group, administered with vehicle (n = 10). Treatments were administered subcutaneously every week for 2 weeks immediately after CCI. To quantify the sensitivity to a tactile stimulus, paw withdrawal in response to a tactile stimulus was measured using von Frey filaments at 0, 1, and 2 weeks after CCI. Von Frey filaments were applied to the plantar surface of the hindpaws for 3 s, and this was repeated three times. Paw withdrawal in response to the stimulus was evaluated by scoring as follows: 0, no response; 1, a slow and/ or slight response to the stimulus; 2, a quick withdrawal response; 3, an intense withdrawal response away from the stimulus. The mean value of the score was adopted as the pain score. After evaluating the response, bilateral femurs were harvested for bone mineral density (BMD) measurements.

The pain score of the CCI side was significantly higher than that of the sham side in all groups (p < 0.05) at each time point. The pain score for the MIN group, but not the ALN group, of the CCI side was significantly lower (p = 0.05) at 0 and 1 week after CCI. Total femoral BMD of the CCI side was significantly lower in the PRG and Control groups than those of the MIN and ALN groups (p < 0.05). No significant difference was identified for BMD between the MIN and ALN groups.

Minodronate showed a significant analgesic effect on chronic pain and suppressed osteoporotic changes caused by CCI.

Robust evidence on the effectiveness of peri-operative local anaesthetic infiltration (LAI) is required before it is incorporated into the pain management regimen for patients receiving total knee replacement (TKR). To assess the effectiveness of peri-operative LAI for pain management in patients receiving TKR we conducted a systematic review, fully powered randomised controlled trial (RCT) and economic evaluation.

We searched MEDLINE, Embase and Cochrane databases for RCTs of peri-operative LAI in patients receiving TKR. Two reviewers screened abstracts and extracted data. Outcomes were pain, opioid use, mobilisation, hospital stay and complications. Authors were contacted if required. When feasible, we conducted meta-analysis with studies analysed separately if a femoral nerve block (FNB) was provided.

In the APEX RCT, we randomised 316 patients awaiting TKR to standard anaesthesia which included FNB, or to the same regimen with additional peri-operative LAI (60mls 0.25% bupivacaine plus adrenaline). Post-operatively, all patients received patient-controlled morphine. The primary outcome was joint pain severity (WOMAC-Pain) at 12 months. Patients and outcome assessors were blinded to allocation.

Within APEX, cost-effectiveness was assessed from the health and social-care perspective in relation to quality adjusted life years (QALYs) and WOMAC-Pain at 12-months. Resource use was collected from hospital records and patient questionnaires.

In the systematic review, 23 studies including 1,439 patients were identified. Compared with patients receiving no intervention, LAI reduced WOMAC-Pain by standardised mean difference (SMD) −0.40 (95%CI −0.58, −0.22; p<0.001) at 24 hours at rest and by SMD −0.27 (95%CI −0.50, −0.05; p=0.018) at 48 hours during activity. In three studies there was no difference in pain at any time point between randomised groups where all patients received FNB. Patients receiving LAI spent fewer days in hospital, used less opioids and mobilised earlier. Complications were similar between groups. Few studies reported long-term outcomes.

In the APEX RCT, pain levels in hospital were broadly similar between groups. Overall opioid use was similar between groups. Time to mobilisation and discharge were largely dependent on local protocols and did not differ between groups. There were no differences in pain outcomes between groups at 12 months.

In the economic evaluation, LAI was marginally associated with lower costs. Using the NICE £20,000 per QALY threshold, the incremental net monetary benefit was £264 (95%CI, −£710, £1,238) and the probability of being cost-effective was 62%.

Although LAI appeared to have some benefit for reduced pain in hospital after TKR there was no evidence of pain control additional to that provided by femoral nerve block, however it would be cost-effective at the current NICE thresholds.

Robust evidence on the effectiveness of peri-operative local anaesthetic infiltration (LAI) is required before it is incorporated into the pain management regimen for patients receiving total hip replacement (THR). We assessed the effectiveness of LAI using a systematic review and a fully powered randomised controlled trial (RCT) with economic evaluation.

We searched MEDLINE, Embase and Cochrane databases for RCTs of peri-operative LAI in patients receiving THR. Two reviewers screened abstracts, extracted data, and liaised with authors. Outcomes were pain, opioid use, mobilisation, hospital stay and complications. If feasible, we conducted meta-analysis.

In the APEX RCT, we randomised 322 patients awaiting THR to receive additional peri-operative LAI (60mls 0.25% bupivacaine plus adrenaline) or standard anaesthesia alone. Post-operatively, all patients received patient-controlled morphine. The primary outcome was joint pain severity (WOMAC-Pain) at 12 months. Patients and outcome assessors were blinded to allocation.

Within APEX, cost-effectiveness was assessed from the health and social-care perspective in relation to quality adjusted life years (QALYs) and WOMAC-Pain at 12-months. Resource use was collected from hospital records and patient questionnaires.

In the systematic review, we identified 13 studies (909 patients). Patients undergoing THR receiving LAI experienced greater pain reduction at 24 hours at rest, standardised mean difference (SMD) −0.61 (95%CI −1.05, −0.16; p=0.008) and at 48 hours during activity, SMD −0.43 (95%CI −0.78, −0.09; p=0.014). Patients receiving LAI spent fewer days in hospital, used less opioids and mobilised earlier. Complications were similar between groups. Long-term outcomes were not a focus of these studies.

In the APEX RCT, pain levels in hospital were broadly similar between groups, probably due to patient-controlled analgesia. Opioid use was similar between groups. Time to mobilisation and discharge were largely dependent on local protocols and did not differ between groups. Patients receiving LAI were less likely to report severe pain at 12 months than those receiving standard care, odds ratio 10.2 (95%CI 2.1, 49.6; p=0.004). Complications were similar between groups.

In the economic evaluation, LAI was associated with lower costs and greater cost-effectiveness than standard care. Using a £20,000 per QALY threshold, the incremental net monetary benefit was £1,125 (95%CI £183, £2,067) and the probability of being cost-effective was greater than 98 %.

The evidence suggests that peri-operative LAI is a cost-effective intervention for reducing acute and chronic post-surgical pain after THR.

Around 20% of patients who have total knee replacement find that they experience long-term pain afterwards. There is a pressing need for better treatment and management for patients who have this kind of pain but there is little evidence about how to improve care. To address this gap we are developing a complex intervention comprising a clinic to assess potential causes of a patient's long-term pain after knee replacement and onwards referral to appropriate, existing services. The Medical Research Council recommends that development of complex interventions include several stages of development and refinement and involvement of stakeholders. This study comprises the penultimate stage in the comprehensive development of this intervention. Earlier stages included a survey of current practice, focus groups with healthcare professionals, a systematic review of the literature and expert deliberation.

Healthcare professionals from diverse clinical backgrounds with experience of caring for patients with long-term pain after knee replacement were sent a study information pack. Professionals who wished to participate were asked to return their signed consent form and completed study questionnaire to the research team. Participants rated the appropriateness of different aspects of the assessment process and care pathway from 1–9 (not appropriate to very appropriate). Data were collated and a document prepared, consisting of anonymised mean appropriateness ratings and summaries of free-text comments. This document was then discussed in 4 facilitated meetings with healthcare professional held at the future trial centres. A summary report and revised care pathway was then prepared and sent to participants for further comments.

28 professionals completed the questionnaire and/or attended a meeting. Participants included surgeons, physiotherapists, nurses, pain specialists and rheumatologists. Mean appropriateness scores ranged from 6.9 to 8.4. Taking a score of 7–9 as agreement, consensus was achieved that the assessment should be performed at 3 months post-operative by an extended scope practitioner/nurse, treatment be guided by a standardised assessment of pain, and treatment individualised. There was also agreement that referrals in the care pathway to surgical review, GP and pain clinics were appropriate. Nurse-led/self-monitoring was rated lower (6.9) because of considerations about the need to ensure that patients receive appropriate support, follow-up and referral to other services.

This work demonstrates the research methods that can be used to refine the design of a complex intervention. The process and findings enable refinement of an intervention for patients with long-term pain after knee replacement. The next stage of intervention development will assess the acceptability and reliability of the assessment process, and the usability of the intervention's standard operating procedures. The intervention will then be evaluated by a larger research team in a multi-centre randomised controlled trial, starting in late 2016.

Diffuse noxious inhibitory control (DNIC) works through the “pain-inhibits-pain” principle in which an additional painful (conditioned) stimulus can suppress the initial experienced pain through the descending and inhibiting pathways. Painful stimulation produced less pain inhibition in patients with knee osteoarthritis patients (KOA) than in controls, suggesting an impaired DNIC function and a loss of endogenous pain modulation. Electroacupuncture (EA) is widely used to treat acute pain associated with KOA, but the available evidence of its benefit on chronification of acute pain is scarce.

This is a single-arm clinical study aims to evaluate the effect of EA on the chronification of pain associated with KOA and provide a profile of various cytokines underlying the pathogenesis of KOA. Participants are recruited through hospital-based recruitment and advertisements, diagnosis was based upon the criteria formulated by the American College of Rheumatology. Each participant was administered with EA (2 mA < current < 5 mA) at the ipsilateral EX-LE5, ST35, ST34 and SP10 for two weeks (once a day, 30 minutes per session, in 5 sessions per week). Visual Analog Scale (VAS), DNIC function, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Numerical Rating Scale (NRS), Emotional Scale (ES) and Present Pain Intensity (PPI) are evaluated before treatment and after 5 to 10 sessions of treatment. Cytokines including GRO, TNF-α, VEGF, IP-10, IL-1β, IL-17, IL-8, MCP-1 and IL-10 levels in plasma were measured using a Human Cytokine/Chemokine Magnetic Bead Panel on MAGPIX instrument before and after two weeks of treatment.

A total of 39 patients with KOA were enrolled in our study (age: 63.46±9.89 years; height: 1.63±0.07 m; BMI: 22.83±2.89), all of them completed the trial. After 5 sessions of EA treatment, a significant decrease of VAS, WOMAC scores, NRS, ES and PPI was detected, but no significant difference in DNIC was observed. After two weeks' treatment, all clinical parameters (VAS, DNIC, WOMAC, NRS, ES, PPI) reduced significantly when compared with baseline; GRO, IL-17A, IL-1b, IL-8, MCP-1, TNF-a, VEGF levels in plasma reduced significantly while IL-10 and IP-10 concentrations were elevated.

This study appeared to provide evidence that EA was effective in improving chronic pain associated with KOA through repairing the impaired DNIC function and down-regulation of OA detrimental cytokines. A randomized controlled prospective study with large sample size is required to clarify the effect of EA in reversing the chronification of pain in KOA.