Introduction. The fracture healing outcome is often evaluated via ex vivo testing of the fracture callus. However, there is only a small time window, where the callus stiffness is significantly different, i.e. a delayed fracture healing might be undetected if the time point of sacrifice is improper. The aim of this study was to develop an in vivo monitoring concept, which allows determining the fracture callus stiffness in vivo over the whole healing time in rats. Hypothesis. The fracture callus stiffness can be monitored by measuring the deformation of the external fixation device during gait analysis at several healing time points. Materials & Methods. The right femurs of sixteen wistar rats were osteotomized and stabilized with an external fixation device (stiffness 119 N/mm or 32 N/mm). The fixator body was instrumented with a stain gauge to measure the deformation. Gait analysis was performed once per week in a gait wheel equipped with a ground reaction force measuring device. Results. The deformation of the fixation devices decreased over the healing time indicating an increase of the callus stiffness. The flexible fixated group showed a later increase of the callus stiffness indicating a delay in fracture healing. Discussion & Conclusion. Measuring the deformation of the fixator and gait analysis provides a powerful tool to monitor the fracture healing process in rats. With this, it is possible to detect a delayed fracture healing process more reliable than with ex vivo analyses

Introduction. Modular tantalum augments have been introduced to manage severe bone defects in hip and knee revision surgery. The porous surfaces of tantalum augments are intended to enhance osseointegration and a number of studies have documented their excellent biocompatibility. However, the characteristics of tantalum augment osseointegration on human ex vivo specimens from re-revision procedures have not been reported so far. Methods. Out of a total number of 324 hip and knee revisions with a tantalum augment performed in our institution between 2007 and 2010 four patients had to be re-revised at a mean followup time of 15 months. The causes for re-revision were a periprosthetic acetabular fracture in one, a loosening of a tibial component in one and periprosthetic hip infections in two cases. To characterize osseointegration of the tantalum augments, they were removed during revision surgery and subjected to undecalcified processing. All specimens were analysed by contact radiography, histology (toluidine blue, von Kossa) and quantitative histomorphometry. Results. In all specimens trabecular ingrowth was apparent along the former bone-augment-interface. The depth of bone ingrowth into the porous microarchitecture of the augments reached up to 2000 μm. Thin-section analysis revealed scattered and partially mineralized bone forming units within the interior of the augments. Conclusions. To the best of our knowledge this is the first histomorphometric analysis on the osseointegration of tantalum augments in human ex vivo specimens. In the presented series porous tantalum showed excellent osteoconductive characteristics on the histological level. These early ex vivo histological findings are promising, but structural analysis of later re-revision cases is needed

Clinical evidence that patients with type 2 diabetes mellitus (T2DM) have increased risk of fractures is reported. Furthermore, thiazolidinediones, used to treat T2DM increases the risk of secondary osteoporosis & subsequent fractures. The osteogenic potency of metformin is reported in vitro, few studies have investigated the effects of metformin on bone mass and fracture healing in vivo. We aimed to investigate the effects of metformin on fracture healing in vivo. Method. 20 female Wistar rats aged 3 months were randomly divided in two groups, one group receiving saline, the other group receiving metformin administered orally via the drinking water at a concentration of 2mg/ml. After 4 weeks of metformin treatment, a mid-diaphyseal, open External fixation fracture was performed. Rats were sacrified 4 weeks later. Right contralateral tibia and left osteotomised femora were excised, bone architecture analysed by micro-CT in the right tibia. Results. No significant differences were noted between the two groups. Fracture callus volume and mineral content after 4 weeks were similar in metformin and saline groups. Discussion Our results indicate that while metformin has no adverse effects on bone, it does not promote bone mass, as suggested by in vitro studies. This confirms clinical data which have not shown direct links between metformin and decreased fracture risk

The osteointegration of a new three-dimensional reticular titanium material, Trabecular Titanium™, was assessed using a bilateral cancellous (distal femur, proximal tibia) and cortical (tibia diaphysis) bone drill hole model in 18 sheep. TT is a novel Ti6Al4V material characterized by a high open porosity and composed of multi-planar regular hexagonal cells. Two 5.0 mm diameter, 12 mm long cylinders (TT1 & TT2) of two different porosities (TT1:650 μm, TT2:1250 μm) were tested and compared to two solid predicate 5.0 mm diameter, 12 mm long Ti cylinders (PT1 & PT2) coated with porous Ti (PT1: vacuum-plasma spray coating; PT2: inert-gas shielding arc spray coating). Each implant type was surgically implanted at 4 separate locations in each sheep (16 implants per sheep). Three timepoints of 4, 16 and 52 weeks (n=6 sheep per timepoint) were used. Bone-implant interface was analyzed ex vivo by the determination of: 1) the shear strength (SS) measured during a push out test, 2) the percentage of bone in-growth (%B) using histomorphometry, 3) the bone apposition rate using fluorochrome labelling analysis and 4) the bone-implant contact using backscattered scanning electron microscopy (SEM). An ANOVA with a Bonferroni Post hoc test were used to detect differences between tested and predicate implants. P values 0.05 were considered significant. At 4 weeks, 5 out of the 6 TT1 could be pushed out of the cortical bone (COB) samples. The remaining TT1 collapsed during testing. All TT1 could be pushed of the cancellous bone (CAB) samples. Four out of the 6 TT2 could be pushed out of CAB and of the COB samples. At 16 and 52 weeks, only one TT1 and one TT2 could be pushed out of the bone samples, the remaining implants collapsed during testing. All the PTs were successfully pushed out at all timepoints. The mean %B of PT1 and PT2 did not significantly increase over time. For both materials, the mean %B ranged between 1.7% and 4.4% at 4 weeks and between 5.7% and 6.5% at 52 weeks. The mean %B of TT1 significantly increased over time in both COB (10.2% at 4 weeks, 46.2% at 16 weeks, 50.5% at 52 weeks) and CAB (5.8%, 23.9%, 24.3%). Similarly, the mean %B of TT2 significantly increased over time in both COB (7.8%, 48.6%, 65%) and CAB (4.5%, 24.1%, 38.6%). Bone apposition rates for the TT implants remained superior to 2 μm/day for the entire duration of the study. SEM showed an intimate bone-implant contact for all implant types at all timepoints. At 16 and 52 weeks, histomorphometry revealed an extensive osteointegration of the TT specimens. Bone-implant interface strength was so high for the TT implants that they could not be pushed out of the bone samples. The results of this study would indicate that the TT implants provide a good scaffold for bone in-growth

Aims

The Intraosseous Transcutaneous Amputation Prosthesis (ITAP) may improve quality of life for amputees by avoiding soft-tissue complications associated with socket prostheses and by improving sensory feedback and function. It relies on the formation of a seal between the soft tissues and the implant and currently has a flange with drilled holes to promote dermal attachment. Despite this, infection remains a significant risk. This study explored alternative strategies to enhance soft-tissue integration.

Magnesium calcium alloys are promising candidates for an application as biodegradable osteosynthesis implants [1,2]. As the success of most internal fracture fixation techniques relies on safe anchorage of bone screws, there is necessity to investigate the holding power of biodegradable magnesium calcium alloy screws. Therefore, the aim of the present study was to compare the holding power of magnesium calcium alloy screws and commonly used surgical steel screws, as a control, by pull-out testing.

Magnesium calcium alloy screws with 0.8wt% calcium (MgCa0.8) and conventional surgical steel screws (S316L) of identical geometries (major diameter 4mm, core diameter 3mm, thread pitch 1mm) were implanted into both tibiae of 40 rabbits. The screws were placed into the lateral tibial cortex just proximal of the fibula insertion and tightened with a manual torque gauge (15cNm). For intended pull-out tests a 1.5mm thick silicone washer served as spacer between bone and screw head. Six animals with MgCa0.8 and four animals with S316L were followed up for 2, 4, 6 and 8 weeks, respectively. Thereafter the rabbits were sacrificed. Both tibiae were explanted, adherent soft tissue and new bone was carefully dissected around the screw head. Pull-out tests were carried out with an MTS 858 MiniBionix at a rate of 0.1mm/sec until failure of the screw or the bone. For each trial the maximum pull-out force [N] was determined. Statistical analysis was performed (ANOVA, Student's t-test).

Both implant materials were tolerated well. Radiographically, new bone was detected at the implantation site of MgCa0.8 and S316L, which was carefully removed to perform pull-out trials. Furthermore, periimplant accumulations of gas were radiographically detected in MgCa0.8. The pull-out force of MgCa0.8 and S316L did not significantly differ (p = 0.121) after two weeks. From 6 weeks on the pull-out force of MgCa0.8 decreased resulting in significantly lower pull-out values after 8 weeks. Contrary, S316L pull-out force increased throughout the follow up. Thus, S316L showed significantly higher pull-out values than MgCa0.8 after 4, 6 and 8 weeks (p<0.001).

MgCa0.8 showed good biocompatibility and pull-out values comparable to S316L in the first weeks of implantation. Thus, its application as biodegradable osteosynthesis implant is conceivable. Further studies are necessary to investigate whether the reduced holding power of MgCa0.8 is sufficient for secure fracture fixation. In addition, not only solitary screws, but also screw-plate-combinations should be examined over a longer time period.

Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce peri-operative bleeding. Increasingly, topical administration as an intra-articular injection or peri-operative wash is being administered at concentrations between 10–100mg/ml. This study investigated effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. Tendon, synovium and cartilage obtained from routine orthopaedic surgeries were used ex vivo or cultured for in vitro studies using various concentrations of TXA. They were stained with 5-chloromethylfluorescein diacetate and propidium iodide and imaged using confocal microscopy to identify the proportion of live and dead cells. The in vitro effect of TXA on primary cultured tenocytes, synovial like fibroblast (FLS) cells and chondrocytes was investigated using cell viability assays (MTT), fluorescent microscopy and multi-protein apoptotic arrays for cell death. There was significant (p<0.01) increase in cell death in all tissue treated with 100mg/ml TXA, ex vivo. MTT assays revealed significant (p<0.05) decrease in cell viability following treatment with 50 or 100mg/ml of TXA within 4 hours of all cell types cultured in vitro. Additionally, there was significant (p<0.05) increase in cell apoptosis detected by fluorescent microscopy within 1 hour of exposure to TXA. Furthermore, multi-protein apoptotic arrays detected increased apoptotic proteins within 1 hour of TXA treatment in tenocytes and FLS cells. Our study provides evidence of TXA cytotoxicity to human peri-articular tissues ex vivo and in vitro at concentrations and durations of treatment routinely used in clinical environments. Clinicians should therefore show caution when considering use of topical TXA administration

Osteoinductive bone substitutes are in their developmental infancy and a paucity of effective grafts options persists despite clinical demand. Bone mineral substitutes such as hydroxyapatite cause minimal biological activity when compared to osteoinductive systems present biological growth factors in order to drive bone regeneration. We have previously demonstrated the in-vitro efficacy of a bioengineered system at presenting growth factors at ultra low-doses. This study aimed to translate this growth factor delivery system towards a clinically applicable implant. Osteoinductive surfaces were engineered using plasma polymerisation of poly(ethyl acrylate) onto base materials followed by adsorption of fibronectin protein and subsequently growth factor (BMP-2). Biological activity following ethylene oxide (EO) sterilisation was evaluated using ELISAs targeted against BMP-2, cell differentiation studies and atomic force microscopy. Scaffolds were 3D printed using polycaprolactone/hydroxyapatite composites and mechanically tested using a linear compression models to calculate stress/strain. In-vivo analysis was performed using a critical defect model in 23 mice over an 8 week period. Bone formation was assessed using microCT and histological analysis. Finally, a computer modelling process was developed to convert patient CT images into surface models, then formatted into 3D-printable scaffolds to fill critical defects. Following EO sterilisation, there was no change in scaffold surface and persistent availability of growth factors. Scaffolds showed adequate porosity for cell migration with mechanical stiffness similar to cancellous bone. Finally, the in vivo murine model demonstrated rapid bone formation with evidence of trabecular remodelling in samples presenting growth factors compared to controls

Introduction. Nonunion is a common and costly fracture outcome. Intricate reciprocity between angiogenesis and osteogenesis means vascular cell-based therapy offers a novel approach to stimulating bone regeneration. Hypothesis. The current study compared early and late outgrowth endothelial progenitor cell subtypes (EPCs vs OECs) for fracture healing potential in vitro and in vivo. Methods. Primary cell cultures were isolated and characterized by endothelial assays, immunosorbent assays, and multi-color flow cytometry. Co-cultures of EPC subtypes with/without primary osteoblasts (pObs) were analyzed for tube length and connectivity. In vivo, EPCs or OECs (1×10. 6. ) seeded on a gelfoam scaffold were implanted in a rat model of nonunion. Radiography was used to monitor callus formation. Results. OECs expressed more BMP-2 and less VEGF than EPCs (p<0.05). Analysis of surface markers showed decreased CD34+/CD133+/Flk-1+, CD133+ and CD45+ populations in OECs while CD34+/CD31+/Flk-1+ cells increased. pObs significantly inhibited the strong tubulogenesis of OECs while enhancing connectivity and sprout length of EPCs. In vivo, 0/6 scaffold-control and 1/5 OEC rats achieved union at 10 weeks. In comparison, all EPC rats achieved full or partial union. Discussion and Conclusion. Despite favorable tubulogenic and osteoconductive profiles of OECs, EPCs display enhanced fracture healing in vivo. Differences in CXCR4 expression and cell-mediated effects may contribute to this result

Antimicrobial resistance (AMR) is projected to result in 10 million deaths every year globally by 2050. Without urgent action, routine orthopaedic operations could become high risk and musculoskeletal infections incurable in a “post-antibiotic era.” However, current methods of studying AMR processes including bacterial biofilm formation are 2D in nature, and therefore unable to recapitulate the 3D processes within in vivo infection. Within this study, 3D printing was applied for the first time alongside a custom-developed bioink to bioprint 3D bacterial biofilm constructs from clinically relevant species including Staphylococcus aureus (MSSA), Methicillin-resistant staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa. Bacterial viability and biofilm formation in bioprinted constructs was excellent, with confocal laser scanning microscopy (CSLM) used to demonstrate biofilm production and maturation over 28 days. Bioprinted 3D MRSA and MSSA biofilm constructs had greater resistance to antimicrobials than corresponding two-dimensional (2D) cultures. Thicker 3D E.coli biofilms had greater resistance to tetracycline than thinner constructs over 7 days of treatment. Raman spectroscopy was also adapted in a novel approach to non-invasively diagnose 3D bioprinted biofilm constructs located within a joint replacement model. In conclusion, mature bacterial biofilm constructs were reproducibly 3D bioprinted for the first time using clinically relevant bacteria. This methodology allows the study of antimicrobial biofilm penetration in 3D, and potentially aids future antimicrobial research, replicating joint infection more closely than current 2D culture models. Furthermore, by deploying Raman spectroscopy in a novel fashion, it was possible to diagnose 3D bioprinted biofilm infections within a joint replacement model

Objectives. Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. Materials and Methods. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. Results. The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). Conclusions. This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials. Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427–435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1

Aims

Our objective was to conduct a systematic review and meta-analysis, to establish whether differences arise in clinical outcomes between autologous and synthetic bone grafts in the operative management of tibial plateau fractures.

Recent findings about UHMWPE oxidation from in vivo stresses lead to the need of a better understanding of which anti-oxidant additivation method is the best option for the use in orthopaedic field. A GUR 1050 crosslinked Vitamin E - blended UHMWPE has been investigated, to provide an accurate outline of its properties. DSC and FTIR measurements, together with ageing and tensile tests were performed on compression moulded blocks, as well as biocompatibility tests, including implantation on rabbits. Moreover, wear simulations on finished components (Delta acetabular liners) have been completed. All the test procedures have been repeated for a reference material, a GUR 1050 crosslinked and remelted standard UHMWPE (commercial name UHMWPE X-Lima), and the outcomes have been compared to the crosslinked Vitamin E - blended UHMWPE ones. On the additivated UHMWPE, we found a ultimate tensile strength of 43 MPa, a yield strength value of 25 MPa, and an elongation to breakage equal to 320%. The degree of cristallinity was 45 ± 2%, and no signal of creation of oxidation products was detected up to 2000 h of permanence in oxidant ambient after the ageing test. The reference material showed comparable mechanical resistance values (∗ = 40 MPa, y = 20 MPa, 350% elongation), a cristallinity of 46 ± 2%, and the creation of oxidation products starting from 700 h in oxidant ambient. The biocompatibility tests indicate that the additivated material is biocompatible, as the reference X-Lima UHMWPE. Wear tests gave a wear rate of 5,09 mg/million cycles against 6,13 mg/million cycles of the reference material, and no sign of run in wear rate. Our results indicate that there is no change in mechanical properties in respect to the reference material. This is confirmed by DSC measurements, that show no change in cristallinity. The blend between polymer and additive assures an uniform concentration of Vitamin E across the whole thickness of the moulded block, and ageing test results on additivated UHMWPE have shown that the material possess a superior resistance to degradation phenomena. Biocompatibility assess that the presence of Vitamin E is not detrimental for the in vivo use of the material, and wear results indicate a better wear resistance of the material, especially in the first stages of the wear process. From these considerations, it can be concluded that the material, in respect to the standard UHMWPE, is highly resistant to oxidation phenomena, therefore it is expected to have superior in vivo endurance performance

INTRODUCTION. Whilst there is a great deal of research on hip implants, few studies have looked at implant orientation and the subsequent effect upon the wear performance of a hip resurfacing. This study aimed to measure implantation angles through radiographic analysis and linear wear for retrieved acetabular cups in order to investigate possible causal links between wear and implant orientation. MATERIALS & METHODS. Seventy Birmingham Hip Resurfacing (Smith & Nephew, UK) cups with known time in vivo were analysed. Linear wear of retrieved cups were assessed using a Talyrond 290 roundness machine. Deviations from the characteristic manufactured profile, was identified as a region of wear. Polar measurements across the wear region were taken to determine wear. The linear wear rate (LWR) of a component was defined as the linear wear (μm) divided by the duration of the implant life in vivo (years). Cups which showed the wear crossing over the edge of the cup were classified as edge loaded (EL). For all non-edge loaded (NEL) cups, the wear area was within the bearing surface. Cup orientation angles were conducted for 31 cups. This was determined by superimposing BHR models of appropriate size, generated by CAD ProEngineer Wildfire 4, onto anterior-posterior x-rays. Anatomical landmarks and specific features of the BHR were used as points of reference to determine cup version and inclination angles. RESULTS. Forty two cups were classed as EL, showing regions of wear extending beyond the edge of the cup. Twenty eight were classed as NEL. The EL group had an average LWR of 25.4(±8.05 95% CL) μm/yr, whilst the NEL group generated an average LWR of 1.45 (±0.34 95% CL) μm/yr, a statistically significant difference (p<0.05).a Following radiographic analysis, 23 cups were classed as EL, showing regions of wear extending beyond the edge of the cup. Eight were classed as NEL. Cups in the EL group showed average inclination and version angles of 54.35° (±5.37° 95% CL) and 22.43° (±5.23° 95% CL). Average inclination and version angles of cups in the NEL group were 45° (±7.20° 95% CL), and 14.88° (±3.38° 95% CL) respectively. Inclination and version angles between the two groups were statistically significant (p<0.05). DISCUSSION. Through linear wear and radiographic analysis, the current study has shown that mal-positioned resurfacing devices classed as EL had higher linear wear than the NEL cups. Edge loaded cups examined in this study showed significantly higher inclination and anteversion (p<0.05) than the non-edge loaded devices. This indicates that component wear is closely associated with in vivo orientation. The success of any implant is dependent upon implant orientation both in version and inclination angles. The correct implant orientation will help to ensure that wear occurs within the bearing surfaces, maintaining an optimal lubrication regime and low wear

Aims

The aim of this study was to determine the immediate post-fixation stability of a distal tibial fracture fixed with an intramedullary nail using a biomechanical model. This was used as a surrogate for immediate weight-bearing postoperatively. The goal was to help inform postoperative protocols.

Kirschner wires are commonly used in paediatric fractures, however, the requirement for removal and the possibility of pin site infection provides opportunity for the development of new techniques that eliminate these drawbacks. Bioabsorbable pins that remain in situ and allow definitive closure of skin at the time of insertion could provide such advantages. Three concurrent studies were performed to assess the viability of bioabsorbable pins across the growth plate. (1) An epidemiological study to identify Kirschner wire infection rates. (2) A mechanical assessment of a bioabsorbable pin compared to Kirschner wires in a simulated supracondylar fracture. (3) The insertion of the implants across the physis of sheep to assess effects of the bioabsorbable implant on the growth plate via macroscopic, pathohistological and micro-CT analysis. An infection rate of 8.4% was found, with a deep infection rate of 0.4%. Mechanically the pins demonstrated comparable resistance to extension forces (p=) but slightly inferior resistance to rotation (p=). The in vivo component showed that at 6 months: there was no leg length discrepancy (p=0.6), with micro-CT evidence of normal physeal growth without tethering, and comparable physeal width (p=0.3). These studies combine to suggest that bioabsorbable pins do not represent a threat to the growth plate and may be considered for physeal fracture fixation

Introduction. Oxidized zirconium (OxZr) is used as a ceramic surface for femoral components in total knee arthroplasty (TKA). The aim of this study was to investigate its performance by examining retrieved femoral components and their corresponding PE inserts in matched comparison with conventional chrome/cobalt/molybdenum alloy (CrCoMo). Methods. 11 retrieved posterior stabilized (PS) TKA with an OxZr femoral component were included. From a cohort of 56 retrieved TKA with CrCoMo femoral components, pairs were matched according to duration of implantation, patient age, reason for revision, and BMI. The retrieved tibial polyethylene (PE) inserts were analyzed for wear using the Hood classification. Femoral components were optically viewed at 8–32x magnification and screened for scratching, pitting, delamination, and striation. Profilometry was performed to measure surface roughness of the OxZr components using a non-contact white light profiler. Results. The prostheses were in situ for a mean of 18.5±10.6 (OxZr) and 19.5±14.3 (CrCoMo) months (p=0.41). None of these cases were revised for problems directly related to the use of OxZr. There was one reaction to the implant in the CrCoMo group. The average wear of the tibial PE inserts was significantly lower with OxZr components (41.5±16.8 vs. 60.1±22.0, p=0.01). The average wear score in the visual analysis of the femoral components was significantly lower for the OxZr (1.6±1.3 vs. 9.5±0.6, p=0.005). Discussion and Conclusion. Femoral components made of OxZr are less sensitive to in vivo wear damage than those of CrCoMo. PE inlays show significantly less in vivo wear damage in combination with an OxZr femoral component

Engineered bone tissue to recreate the continuity of damaged skeletal segments is one of the field of interest of tissue engineering. Trabecular titanium has very good mechanical properties and high in vitro and in vivo biocompatibility: it can be used in biomedical applications to promote osteointegration demonstrating that it can be successfully used for regenerative medicine in orthopaedic surgery (1). Purpose of this investigation was to evaluate the behavior of adipose tissue derived stem cells (hASCs) cultured on scaffolds of Trabecular TitaniumTM (Lima-Lto) (TT). hASCs are considered to be multipotent mesenchymal stem cells that are easily induced to differentiate into functional osteoblasts both in vitro and in vivo (2). The hASCs were obtained from the subcutaneous adipose tissue of healthy donors during total hip replacement procedures after digestion with collagenase. They were seeded on monolayer and on the TT scaffolds, and incubated at 37 degrees C in 5% CO2 with osteogenic medium or control medium. The expression of bone-related genes using RT-PCR, time course of alkaline phosphatase activity and morphological investigation with Scanning Electron Microscopy (SEM) were performed to evaluate the osteogenic differentiation of hASCs. Alkaline phosphatase activity, marker of the differentiation toward the osteogenic pattern, was significantly higher in hASCs grown with osteogenic medium than in cells grown with control medium, both in monolayer and TT scaffolds; moreover, also alkaline phosphatase of hASCs grown on TT scaffolds in the presence of control medium increased with time, differently from that of cells grown on monolayer. The osteogenic differentiated hASCs expressed the bone-related genes type I collagen, osteocalcin, Runx-2 and alkaline phosphatase. SEM observations showed that hASCs differentiated toward osteoblast-like cells: they produced a big amount of extracellular matrix that covered the surface of the porous scaffolds with bridges between the pore walls. These data suggest that hASCs are able to adhere to TT scaffolds, to acquire an osteoblastic phenotype and to produce abundant extracellular matrix, with but also without osteogenic medium. We can therefore conclude that this material carries osteinductive properties being responsible of ostegenic differentiation; consequently, this scaffold/cells construct is effective to regenerate damaged tissue and to restore the function of bone tissue

Introduction. In total hip arthroplasty ceramic on ceramic bearing couples are used more and more frequently and on a wordwide basis. The main reason of this choice is reduction of wear debris and osteolysis. The tribological properties and the mechanical behaviour of the implanted ceramic must remain the same throughout the patient's life. The aim of this study was to evaluate the resistance of Alumina Matrix Composite to environmental degradation. Material and method. The alumina matrix composite or BIOLOX ® delta is manufactured in Germany by CeramTec. It is made up of 80 vol.% Al2O3, 17 vol.% Yttria Stabilized ZrO2 and 3vol.% strontium aluminate platelets. The zirconia grains account for 1.3 mol.% of the Yttria content. Accelerated aging tests in water steam at 142°C, 134°C, 121°C, and 105°C were performed to evaluate the aging kinetics of the composite. X-ray diffraction was used to determine the monoclinic phase content on the material surface. Phase transformation is associated with weakness and increase in roughness of zirconia ceramic implants. Results. The data below shows average monoclinic contents before and after aging in water vapour according to the ISO standard test (134°C, 2 bars water steam, 10 h) on the surface and inside the 28 mm taper(12/14 taper) femoral ball heads manufactured in alumina ceramic composite. There are precisions concerning the roughness and the load to failure before and after aging concerning 28mm diameter heads. Before Aging 13%+/-3% of Monoclinic content. After 10 H at 134°C23%+/-3% of Monoclinic content the roughness of the polished surface remain the same (5nm+/− 2). The load to failure of 28 mm heads before aging is 76 kN +/− 5kN, and 72 kN +/− 5kN after aging. The results show that although a rise in monoclinic content is predictable after long aging duration in vivo, the impact of the transformation is quite different to monolithic zirconia. A zirconia femoral head exhibits an important increase of roughness from 2 nm to more than 50 nm when submitted to the same duration of ageing. Other tests with hip simulators under severe micro separation have been done to analyse the impact of aging on wear performance. The main wear zone on femoral heads underwent a phase transformation from tetragonal to monoclinic (23% monoclinic) at 5 milion cycles duration without any change in roughness after 5Mc duration. Conclusion. This experimental testing program has enabled a prediction for the long-term in vivo environmental resistance of prostheses made out of Alumina Matrix Composite. The substantial improvement in mechanical properties and the excellent wear behaviour, even under severe microseparation conditions has been clinically confirmed. Today more than 960,000 ceramic ball heads and more than 450 000 ceramic inserts made of the alumina matrix composite have been implanted. Additionally, due to enhanced mechanical behaviour, new applications in orthopaedics are possible

INTRODUCTION. Analysis of retrieved ceramic components have shown areas of localized ‘stripe wear’, which have been attributed to joint laxity and/or impingement resulting in subluxation of the head, causing wear on the edge of the cup. Studies have been conducted into the effects of mild subluxation, however few in vitro tests have looked at severe subluxation. The aim of this study was to develop a more clinically relevant subluxation protocol. MATERIALS & METHODS. Seven (Subluxation n=4; standard test n=3) of 36mm Biolox Forte (R3, Smith & Nephew) ceramic devices were tested for 0.5m cycles (mc). Two of the subluxed joints were further tested to 1 Mc. The devices were subjected to subluxation under standard testing conditions. The flex/ext was 30° and 15° respectively, with internal/external rotation of ±10°. The force was Paul type stance phase loading with a maximum load of 3 kN, and a standard ISO swing phase load of 0.3 kN at 1 Hz. The test was conducted on a ProSim hip joint wear simulator (SimSol, UK). The simulator is equipped with a novel mechanism to achieve translation of the head, to achieve subluxation. During the ISO swing phase load of 0.3kN, a controlled lateral force required for the translation of the head is applied by a cam mechanism, head retraction then occurs during heel strike. The lubricant used was new born calf serum diluted with de-ionised water to achieve average protein concentration of 20 g/l, with 0.2 wt % concentration NaN3, and changed every 250k cycles. Measurements have been taken at 0.5 & 1 mc stages. RESULTS. Linear wear measurements conducted on the subluxed joints resulted in stripe wear similar to that reported in vivo. Average length, width and depth dimensions were 25.34±1.96 mm, 8±1.60 mm and 16.95±3.87 μm (± 95% CL) respectively. Linear wear at 0.5 Mc for standard joints, were undistinguishable from the original profile. Gravimetrically, weight loss was undetectable for joints tested under standard conditions. The volume loss of the joints under subluxation was 1.9± 0.7 mm3 at 0.5 mc. Two joints tested to 1mc generated an average volume loss of 3.1±2.3 mm3. The stripe wear length, width and depth at 1 Mc were 25.30±3.33mm, 8±3.92mm and 35±17.07 μm respectiveley. DISCUSSION. The current study presents test results of a hip joint simulator with a novel subluxation mechanism to simulate severe and clinically relevant hip joint. Past techniques have had to reduce the swing phase load to achieve stripe wear patches of varying size and depth. The subluxed joints produced significantly higher volumetric wear than the standard joints. Dimensional measurements in terms of length, width and depth of wear patches of subluxed joints generated similar results to that which have been observed following retrieval analysis. Tests that can simulate different types of activity in hip joint simulators will help to improve the design and understanding of implant behaviour in vivo