Cite this article:
Cartilage repair in terms of replacement, or
regeneration of damaged or diseased articular cartilage with functional tissue,
is the ‘holy grail’ of joint surgery. A wide spectrum of strategies
for cartilage repair currently exists and several of these techniques
have been reported to be associated with successful clinical outcomes
for appropriately selected indications. However, based on respective
advantages, disadvantages, and limitations, no single strategy, or
even combination of strategies, provides surgeons with viable options
for attaining successful long-term outcomes in the majority of patients.
As such, development of novel techniques and optimisation of current techniques
need to be, and are, the focus of a great deal of research from
the basic science level to clinical trials. Translational research
that bridges scientific discoveries to clinical application involves
the use of
Tendinopathy is a debilitating musculoskeletal
condition which can cause significant pain and lead to complete rupture
of the tendon, which often requires surgical repair. Due in part
to the large spectrum of tendon pathologies, these disorders continue
to be a clinical challenge.
Objectives. The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture
Objectives. The primary purpose of this meta-analysis was to determine whether statin usage could reduce the risk of glucocorticoid-related osteonecrosis in
Objectives. We studied subchondral intraosseous pressure (IOP) in an
Aim. Treatment of infected and non-infected non-unions remain a major challenge after orthopedic fracture-related surgery. In clinical practice, several revision surgeries are usually required, including a radical debridement and exchange of implants, to control or even eradicate the infection to finally achieve bone healing. However, a clear treatment algorithm in clinical practice may be difficult to follow due to the heterogeneous patient population. Thus, so controlled settings for research purposes is better achieved in standardized animal studies. So far, there exists no multi-stage
Objectives. Our objective in this article is to test the hypothesis that
type 2 diabetes mellitus (T2DM) is a factor in the onset and progression
of osteoarthritis, and to characterise the quality of the articular
cartilage in an appropriate rat model. Methods. T2DM rats were obtained from the UC Davis group and compared
with control Lewis rats. The diabetic rats were sacrificed at ages
from six to 12 months, while control rats were sacrificed at six
months only. Osteoarthritis severity was determined via histology
in four knee quadrants using the OARSI scoring guide. Immunohistochemical
staining was also performed as a secondary form of osteoarthritic
analysis. Results. T2DM rats had higher mean osteoarthritis scores than the control
rats in each of the four areas that were analysed. However, only
the results at the medial and lateral femur and medial tibia were
significant. Cysts were also found in T2DM rats at the junction
of the articular cartilage and subchondral bone. Immunohistochemical
analysis does not show an increase in collagen II between control
and T2DM rats. Mass comparisons also showed a significant relationship
between mass and osteoarthritis score. Conclusions. T2DM was found to cause global degeneration in the UCD rat knee
joints, suggesting that diabetes itself is a factor in the onset
and progression of osteoarthritis. The immunohistochemistry stains
showed little to no change in collagen II degeneration between T2DM
and control rats. Overall, it seems that the
In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine. Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as
Costoplasty remains useful in the treatment of adolescent idiopathic scoliosis, rib hump and associated chest wall deformities. However traditional costoplasty increases morbidity and blood loss. We examine the feasibility and possible effectiveness of a more conservative costoplasty using an
Purpose: To investigate the effect of pressurizing vertebral bodies during vertebroplasty using different materials in the development of fat embolism (FE) and any associated cardiovascular changes. Polymethylmethacrylate (PMMA) is the material of choice for vertebroplasty (VP). However, PMMA has several disadvantages such as exothermic curing, uncertain long-term biomechanical effects and biocompatibility. As a result alternative materials are being developed to overcome these problems. In order to determine the role of PMMA in the generation of cardiovascular changes following vertebroplasty we compared injection of cement with wax in an
To investigate the effect of pressurizing vertebral bodies during vertebroplasty using different materials in the development of fat embolism (FE) and any associated cardiovascular changes. Polymethylmethacrylate (PMMA) is the material of choice for vertebroplasty (VP). However, PMMA has several disadvantages such as exothermic curing, uncertain long-term biomechanical effects and biocompatibility. As a result alternative materials are being developed to overcome these problems. In order to determine the role of PMMA in the generation of cardiovascular changes following vertebroplasty we compared injection of cement with wax in an
Objectives: Development a giant cell tumor model arising from the mutated mesenchymal cells present in its stroma. This establishes the pathogenic mechanism of giant cell tumor, and allows the evaluation of the possible role of biphosphonates and retinoic acid in medical therapy of giant cell tumor of bone. Introduction: In previous studies our group has shown that mesenchymal stroma contains mesenchymal cells capable of recruiting osteoclasts, and lacking capacity to undergo osteoblastic differentiation. These cells represent the actual neoplastic component of the tumor. In the current study, an attempt was made to establish a giant cell tumor in an
Background: Aseptic loosening of total joint arthroplasty is characterised by osteolysis caused by osteoclasts and macrophages. Osteolysis occurs by acidification and dissolution of hydroxyapatite crystals then proteolysis of the bone collagen matrix. N-Telopeptide (NTx) and deoxypyridinolone (DPD) represent highly specific markers for bone resorption. Aim: To investigate whether urinary NTx and DPD generated in-vivo can be used as bone markers in a small
Summary. Osteoporosis reduces particle-induced osteolysis in rat model. Introduction. Wear particle induced osteolysis is considered to be a vital factor that reduces the life span of joint prosthesis. Osteoporosis is not rare in patients with indication for arthroplasty. However, the influence of osteoporosis on wear particles induced osteolysis is not clear. This study is aimed to explore on this issue by using
The Masquelet or induced membrane technique (IMT) is a two-stage surgical procedure used for the treatment of segmental bone defects. In this technique, the defect is first filled with a polymethyl methacrylate (PMMA) spacer, which triggers the formation of a membrane that will encapsulate the defect. During the second surgery, the spacer is carefully removed and replaced by autologous bone graft while preserving the membrane. This membrane is vascularized, contains growth factors, and provides mechanical stability to the graft, all of which are assumed to prevent graft resorption and promote bone healing. The technique is gaining in popularity and several variations have been introduced in the clinical practice. For instance, orthopaedic surgeons now often include antibiotics in the spacer to treat or prevent infection. However, the consequences of this approach on the properties of the induce membrane are not fully understood. Accordingly, in a small
Aim. A gentamicin-eluting biocomposite consisting of hydroxyapatite and calcium sulfate. 1. can provide effective dead space management in chronic osteomyelitis. However, radiographic follow-up after implantation of this novel material has consistently shown evidence of several unique imaging features previously not described with other comparable bone graft substitutes. Conclusive interpretation of these newly described imaging features is difficult as long term follow-up and histological correlation is not yet available. The aim of this study was to establish a large
Background: The commonest cause of long term failure of total joint arthroplasty is aseptic loosening. As a result, many patients will require complex revision surgery that is not only technically challenging but associated with poorer results. Revisions procedures are also associated with higher morbidity and costs. Aim: To quantify osteolysis in a small
Aim. A gentamicin-eluting biocomposite consisting of hydroxyapatite (HA) and calcium sulphate (CaS)*1 can provide effective dead space management and bone formation in chronic osteomyelitis. However, radiographic follow-up after implantation of this biomaterial has shown imaging features previously not described with other comparable bone graft substitutes. Last year we presented preliminary results with a follow-up of 6 months. Now we present the radiographic, µCT and histological one-year follow-up of the critical-size bone defect model in sheep. The aim of this study was to simulate the clinical situation in a large
Introduction: Currently used small
Introduction: Atrophic nonunion is a well recognised complication of long bone fractures. Clinical trials show that BMP-2 accelerates healing and reduces nonunion in open tibial fractures. We are interested in a natural small molecule that has been previously demonstrated to stimulate angiogenesis in vivo. Our aim is to assess the two treatments in the prevention of nonunion. The small
Aim. Implant-associated osteomyelitis is a devastating complication with poor outcomes following treatment, especially when caused by antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). A large
Purpose: Regeneration of skeletal tissue for fracture repair or during morphogenesis involves common phases of cell proliferation and differentiation. Mesenchymatous precursor cells have multiple origins. These cells can be identified in the bone marrow, in the deep layer of the periosteum and in the endosteum. More recently, the presence of circulating multipotent stem cells has been demonstrated in the general circulation. Their contribution to skeletal regeneration processes is suspected. The experiments we report allow visualisation of the multidirectional differentiation phenomena involving mesenchymatous precursor cells in an
Aims: Little is known about effects of extracorporeal shock wave application (ESWA) on normal bone physiology. Therefore, we investigated ESWA effects on intact distal rabbit femura as an in vivo
The biomechanical evaluation of tendon repair with collagen-based scaffolds in rat model is a common method to determine the functional outcome of the tested material. We introduced a magnetic resonance imaging (MRI) approach to verify the biomechanical test data. In present study different collagen scaffolds for tendon repair were examined. Two collagen test materials: based on bovine stabilized collagen, chemically cross-linked with oriented collagenous fibres (material 1) and based on porcine dermal extracellular matrix, with no cross-linking (material 2) were compared. The animal study was approved by the local review board. Surgery was performed on male Sprague-Dawley rats with a body weight of 400 ± 19 g. Each rat underwent a 5 mm transection of the right Achilles tendon. The M. plantaris tendon was removed. The remaining tendon ends were re-joined with a 5 mm scaffold of either the material 1 or 2. Each scaffold material was sutured into place with two single stiches (Vicryl 4–0, Ethicon) each end. A total of 16 rats (n= 8 each group) were observed for 28 days follow up. The animals were sacrificed and hind limbs were transected proximal to the knee joint. MRI was performed using a 7 Tesla scanner (BioSpec 70/30, Bruker). T2-weighted TurboRARE sequences with an in-plane resolution of 0.12 mm and a slice thickness of 0.7 mm were analysed. All soft and hard tissues were removed from the Achilles tendon-calcaneus-foot complex before biomechanical testing. Subsequently, the specimens were fixed in a materials testing machine (Z1.0, Zwick, Ulm, Germany) for tensile testing. All tendons were preloaded with 1 N and subsequently stretched at a rate of 1 mm/s until complete failure was observed. Non-operated tendons were used as a control (n=4). After 28 postoperative days, MRI demonstrated that four scaffolds (material 1: n=2, material 2: n=2) were slightly dislocated in the proximal part of hind limb. In total five failures of reconstruction could be detected in the tendon repairs (material 1: n=3, material 2: n=2). Tendons augmented with the bovine material 1 showed a maximum tensile load of 57.9 ± 17.9 N and tendons with porcine scaffold material 2 of 63.1 ± 19.5 N. The native tendons demonstrated only slightly higher loads of 76.6 ± 11.6 N. Maximum failure load of the tendon-scaffold construct in both groups did not differ significantly (p < 0.05). Stiffness of the tendons treated with the bovine scaffold (9.9 ± 3.6 N/mm) and with the porcine scaffold (10.7 ± 2.7 N/mm) showed no differences. Stiffness of the native healthy tendon of the contralateral site was significantly higher (20.2 ± 6.6 N/mm, p < 0.05). No differences in the mechanical properties between samples of both scaffold groups could be detected, regardless of whether the repaired tendon defect has failed or the scaffold has been dislocated. The results show that MRI is important as an auxiliary tool to verify the biomechanical outcome of tendon repair in
Long term, secondary implant fixation of Total Disc Replacements (TDR) can be enhanced by hydroxyapatite or similar osseo-conductive coatings. These coatings are routinely applied to metal substrates. The objective of this in vivo study was to investigate the early stability and subsequent bone response adjacent to an all polymer TDR implant over a period of six months in an
Stem cells represent an exciting biological therapy for the management of many musculoskeletal tissues that suffer degenerative disease and/or where the reparative process results in non-functional tissue (‘failed healing’). The original hypothesis was that implanted cells would differentiate into the target tissue cell type and synthesise new matrix. However, this has been little evidence that this happens in live animals compared to the laboratory, and more recent theories have focussed on the immunomodulatory effects via the release of paracrine factors that can still improve the outcome, especially since inflammation is now considered one of the central processes that drive poor tendon healing. Because of the initial ‘soft’ regulatory environment for the use of stem cells in domestic mammals, bone and fat-derived stem cells quickly established themselves as a useful treatment for naturally occurring musculoskeletal diseases in the horse more than 20 years ago (Smith, Korda et al. 2003). Since the tendinopathy in the horse has many similarities to human tendinopathy, we propose that the following challenges and, the lessons learnt, in this journey are highly relevant to the development of stem cells therapies for human tendinopathy: Source – while MSCs can be recovered from many tissues, the predominant sources for autologous MSCs have been bone and fat. Other sources, including blood, amnion, synovium, and dental pulp have also been commercialised for allogenic treatments. Preparation – Delivery – transport of cells from the laboratory to the clinic for autologous ex vivo culture techniques; implantation technique (usually by ultrasound-guided injection to minimise damage to the cells (or, more rarely, incorporated into a scaffold). They can also be delivered by regional perfusion via venous or arterial routes. Retention – relatively poor although small numbers of cells do survive for at least 5 months. Immediate loss to the lungs if the cells are administered via vascular routes. Synovially administered cells do not engraft into tendon. Adverse effects – very safe although needle tracts often visible (but do not seen to adversely affect the outcome). Allogenic cells require careful characterisation for MHC Class II antigens to avoid anaphylaxis or reduced efficacy. Appropriate injuries to treat – requires a contained lesion when administered via intra-lesional injection. Intrasynovial tendon lesions are more often associated with surface defects and are therefore less appropriate for treatment. Earlier treatment appears to be more effective than delayed, when implantation by injection is more challenging. Efficacy - beneficial effects shown at both tissue and whole animal (clinical outcome) level in naturally-occurring equine tendinopathy using bone marrow-derived autologous MSCs Recent (licenced) allogenic MSC treatment has shown equivalent efficacy while intra-synovial administration of MSCs is ineffective for open intra-synovial tendon lesions. Regulatory hurdles – these have been lighter for veterinary treatments which has facilitated their development. There has been greater regulation of commercial allogenic MSC preparations which have required EMA marketing authorisation.
Introduction. Kashin-Beck disease (KBD) is an endemic degenerative osteoarthropathy affecting approximately 3 million people in China (Stone R, 2009). The precise aetiology of KBD is not clear, but the lack of selenium and the pollution of mycotoxins in food are a suspected cause of KBD. In this pilot study, we use a rat model to investigate the effect of low selenium and T-2 toxin on articular cartilage metabolism. Methods. 140 male Sprague-Dawley rats were fed with selenium-deficient or normal diet for 4 weeks to produce a low selenium or normal nutrition status. The rats were then fed for a further 4 weeks with low selenium or normal diets with or without T-2 toxin (100ng per gram body weight per day). The rat knee joints were fixed and paraffin embedded and histological and immunohistochemical staining was performed to analyse the metabolism of articular cartilage. Results. There was increased cell cluster formation in the middle and/or deep zones in rats fed with both diets. However, an apparent cell loss was observed in the low selenium + T-2 toxin group with an apparent increase in caspase-3 staining, indicating the increased cell apoptosis. Moreover, toluidine blue staining was reduced in the low selenium + T-2 toxin group, suggesting a loss of sulphated glycosaminoglycans. Similarly, there was reduced 2B6 and 6C3 staining in the territorial matrix of chondrocytes, indicating a reduced synthesis in 4-sulhated and native CS motifs. In contrast, increased 1B5 staining was observed in the articular cartilage from the low selenium + T-2 toxin group, suggesting a lack of CS sulphatransferase activity. Interestingly, there was increased 7D4 staining in the superficial zone of articular cartilage from low selenium + T-2 toxin group, suggesting an initiation of an osteoarthritis-like lesion. Discussion. These results indicated that low selenium nutrition and T-2 toxin could promote cell apoptosis and disrupt CS-GAG metabolism in ECM of rat articular cartilage in this
Aims: Thrombembolic complications, which include the fat embolism syndrome, are well known consequences of cementless and cemented total hip replacement. Embolic phenomena could be demonstrated clinically and experimentally with both fixation techniques. Methods: We investigated in a standardized
The objective of this study was to investigate the effects of different doses rhBMP-2 on bone healing in an ovine lumbar interbody fusion model. In this study 22 sheep underwent two level lumbar interbody fusion using a ventrolateral approach with secondary dorsal fixation at L1/2 and L3/4. After randomization in one level a PEEK-cage was implanted filled with one of three doses rhBMP-2 (0,5mg; 1mg; 2mg) delivered on an ACS. The other level received an empty PEEK-cage or ACS filled cage. Animals were sacrificed after 3 and 6 months and decalcified histology was performed. This included histomorphological analysis as well as histomorphometry of the tissues within the cage.Introduction
Methods
To evaluate the findings of fusion of titanium interbody cages in a sheep lumbar interbody fusion model. Six sheep underwent lumbar discectomy and fusion at L3-L4 throught transperitoneal approach. An cervical threaded expanding and cylindrical cage packed with bone autografts was placed into intervertebral disc space. The sheeps were killed at 9, 12 and 18 months after surgery. The lumbar spines were excised, trimmed of residual musculature and underwent to plain radiographs and CT scans. The spines were dissected and sectioned using the EXAKT microgrinding device creating parasagittal and coronal sections. Plain radiographs demonstrated no lucent lines around the implants and no change in disc height. CT scans showed mineralized bone within the cages and bone in growth wit anterior bony bridging outside of the cages. Histologic characterizations indicated the presence of mature lamellar bone with osteonic systems filling the central area of the cage. Bone in growth on the surface of the implant is present near the fenestrations alone. A membrane of fibrous tissue layer is present on the external surface of any cage separating bone from the implant. Expanding titanium cages have shown mechanical and biological validity to achieve an optimal interbody fusion. Design of the cage showed a decisive role to provide superior endplate-to-endplate contact for unsurpassed strenght and stability and to agree the achievement of the interbody fusion across its fenestrations.
The present study was performed on 30 mature white rabbits (male range, 2800–3500 gr). The right knees were accepted as study and left knees as control group. Group 1 was received intraarticular 0.1ml sodium hyaluronate treatment, rabbits in group 2 were received 0.1 ml Serum Physiologique once a week for three weeks. Biopsy was taken from both knees at the 3rd and 6th week. Histopathological evaluation was performed by a pathologist who is blind to study according to modified Mankin score.
Doxorubicin-containing pellets were incubated with sarcoma cultures at 37°C for 24 hours. A significantly higher cell death rate(as measured by flow cytometry) was seen in the plates exposed to Doxorubicin compared to those exposed only to plain PMMA, indicating that the Doxorubicin released from the cement pellets retained its cytotoxic capability. PMMA-Doxorubicin cement pellets were implanted in rat tibiae and the animals killed at intervals over three weeks. HPLC analysis showed that this technique produced high concentrations of Doxorubicin adjacent to the implant but negligible systemic levels(heart, kidney, lung, liver). Four groups of rats had sarcomas established in their tibiae and then treated either by excision of tumour and Doxorubicin/PMMA implantation, excision and plain PMMA implantation, excision only or no treatment. The animals were then observed for tumour regrowth. A survival advantage was demonstrated for those animals treated by tumour excision and Doxorubicin/PMMA implantation. Conclusion: These experiments demonstrate that PMMA is an effective medium for the delivery of cytotoxic chemotherapy. This method has scope for early translation to the human situation.
The response of the intervertebral disc to asymmetric forces may accelerate degeneration through changes in the matrix. Macroscopically, the disc sustains structural changes that may play a part in the progression of a scoliotic curve. Molecularly, disc degeneration is the outcome of the action of matrix metalloproteases (MMPs), members of a family of enzymes that bring about the degradation of extracellular matrix components. In this study we measured in vivo the expression of MMPs in a rat scoliotic intervertebral disc and studied the effect of the degree of the deformity on their production. Asymmetric forces were applied in the intervertebral disc between the ninth and tenth vertebrae at the base of a rat tail with the use of a mini Ilizarov external fixator, under anaesthesia. Animals were categorised into three groups according to the degree of the deformity. In group I, the deformity that was applied on the intervertebral disc was 10°, in group II 30°, and in group III 50°. All the animals used were female Wistar rats before adulthood, to take into account the effect of growth for the study of intervertebral disc changes. The intact intervertebral discs outside the fixator were used as controls. After the rats' death on day 35, the tails were prepared and analysed with an immunohistochemical protocol for chromogenic detection and location of MMPs 1 and 12 in tissue sections of the intervertebral discs.Introduction
Methods
Nucleus pulposus (NP) replacements represent a less invasive alternative for treatment of early stage degenerative disc disease (DDD). Hydrogel based NP replacements are of particular interest as they can be injected/implanted using minimally invasive surgical (MIS) techniques to re-establish mechanical integrity and as a scaffold for regeneration. A thiol-modified hyaluronan elastin-like polypeptide (TMHA/EP) hydrogel crosslinked using polyethylene diacrylate has shown promise as a potential NP replacement for DDD in vitro. This study aims to assess the mechanical properties of this hydrogel when injected into an induced early stage DDD porcine model and to determine the optimal injection method for delivery. It is hypothesized that minimally invasive injection of the TMHA/EP material can restore mechanical behaviour of spinal motion segments in early stage DDD. Intervertebral disc (IVD) degeneration was enzymatically induced in L2-L3 and L4-L5 lumbar levels in 10 Yorkshire boars using chondroitinase ABC (n=20 discs). An additional three animals served as healthy controls (n=6 discs). Following a four-week degradation period, the TMHA/EP solution (250microL in a 3:1 weight ratio) was injected into the degenerate NP of 16 discs by one of two MIS techniques: A direct 18G needle injection or a modified kyphoplasty technique (MKT) in which a balloon angiocatheter was inserted through an 11G trocar into the IVD and inflated to create a cavitary defect that was then filled with the hydrogel. Excised motion segments were tested in axial compression under a load of 400N and in axial rotation (AR), lateral bending (LB) and flexion/extension (FE) at 5Nm. Range of motion (ROM), neutral zone (NZ) length, NZ stiffness (NZStiff) and axial compressive stiffness (ACStiff) were quantified.Purpose
Method
In the treatment of nonunions, and other complications of bone repair, an attractive alternative to bone autografts would be the use of a combination of autologous mesenchymal progenitors cells (MSCs), biomaterials and growth factors. Our goal was to determine the therapeutic potential and contribution to the repair process of different sources of mesenchymal stem cells for the treatment of nonunions. The right femur of Sprague-Dawley (SD) rats was stabilized with an aluminum plate (20 mm long, 4 mm wide, 2 mm thick) and four screws (1.5 mm diameter, 8 mm long). A diaphyseal critical size defect was performed (5 mm). Six groups (n=6–8 animals each) were created. A nonunion group (Control group, empty defect); LBA group, live bone allograft; BMP2 group, rhBMP-2 (2 μg) in collagen sponge; PCL group, polycaprolactone scaffold; PMSCs group, PCL scaffold loaded with 5×106 periosteum-derived MSCs; and BMSCs group, PCL scaffold loaded with 5×106 bone marrow-derived MSCs. For cell tracking purposes, LBA and MSCs were derived from SD-GFP transgenic rats. The repair process was followed up by x-rays up to sacrifice, week 10. After sacrifice, femurs were analyzed by micro computed tomography (μCT), histology and immunohistochemistry. For multiple comparisons one-way ANOVA followed by Dunnett”s test for single comparisons was used. Statistical significance was established for p<0.05.INTRODUCTION
METHODS
Conventional imaging techniques lack the ability to objectively assess early stages of intervertebral disc degeneration, characterised by glycosaminoglycan loss. This study shows that MRI T2∗ mapping correlates positively with GAG content and that it provides continuous measurements for disc degeneration. Early degenerative changes arise in the nucleus pulposus (NP) and are characterised by a loss of glycosaminoglycans (GAG). Early disc degeneration (DD) could possibly be treated with upcoming regenerative therapies (e.g. with stem cells and/or growth factors). In order to evaluate degeneration and treatments, a sensitive diagnostic tool is needed. While conventional magnetic resonance imaging (MRI) and x-ray techniques can detect late stages of DD, these techniques lack the ability to detect early degenerative changes. Recently, T2∗ mapping has been proposed as a new technique to evaluate early IVD degeneration, yet the correlation with GAG content and histological features has not been previously investigated. The objective of this study was to determine the value of T2∗ mapping in diagnosing DD by correlating this technique with the biochemical composition of IVDs.Summary Statement
Introduction
There is little information about the effects of extracorporeal shock-wave about application the effects (ESWA) of on normal bone physiology. We have therefore investigated the effects of ESWA on intact distal rabbit femora in vivo. The animals received 1500 shock-wave pulses each of different energy flux densities (EFD) on either the left or right femur or remained untreated. The effects were studied by bone scintigraphy, MRI and histopathological examination. Ten days after ESWA (0.5 mJ/mm2 and 0.9 mJ/mm2 EFD), local blood flow and bone metabolism were decreased, but were increased 28 days after ESWA (0.9 mJ/mm2). One day after ESWA with 0.9 mJ/mm2 EFD but not with 0.5 mJ/mm2, there were signs of soft-tissue oedema, epiperiosteal fluid and bone-marrow oedema on MRI. In addition, deposits of haemosiderin were found epiperiosteally and within the marrow cavity ten days after ESWA. We conclude that ESWA with both 0.5 mJ/mm2 and 0.9 mJ/mm2 EFD affected the normal bone physiology in the distal rabbit femur. Considerable damaging side-effects were observed with 0.9 mJ/mm2 EFD on periosteal soft tissue and tissue within the bone-marrow cavity.
Ten percent of fractures end in delayed or non-union. NSAIDs have been linked to an inhibitory action on fracture repair for three decades yet the mechanism of action remains to be elucidated. Cancer research has identified that NSAIDs impede cell proliferation by inhibiting angiogenesis. It is proposed that a similar mechanism occurs in the induction of NSAID induced non-union. We have investigated this hypothesis in a randomised placebo control trial of the NSAID rofecoxib using a murine femoral fracture. All animals had an open femoral fracture treated using an external fixator. Outcomes measures included x-ray, histology and biomechanical testing, with laser Doppler used to assess blood flow across the fracture gap. Radiology showed similar healing patterns in both groups; however, at the later stages (day 32) the NSAID group had significantly poorer healing. Histological analysis showed that controls healed quicker (days 24 and 32), with more callus (day 8) and less fibrous tissue (Day 32). Biomechanical testing showed controls were stronger at day 32. Both groups exhibited a similar pattern of blood flow; however NSAIDs exhibited a lower median flow from day 4 onwards (significant at days 4, 16 and 24). Positive correlations were demonstrated between both histological and radiographic assessments of healing, with increasing blood flow. NSAID animals exhibited lower flows and poorer healing by all outcomes. Regression analysis demonstrates, however, that the negative effect of NSAIDs on fracture repair is independent of its inhibitory action on blood flow. COX-2 inhibitors are marketed as having cleaner side effect profiles and are widely used in trauma patients. Following development of a novel method of analysing functional vascularity across a fracture gap, we have demonstrated that the COX-2 inhibitor rofecoxib has a significant negative effect on blood flow at the fracture gap alongside inhibiting fracture repair.
In patients with conventional metal-on-Polyethylene (MoP) hip replacements, osteolysis can occur in response to wear debris. During revision hip surgery, surgeons usually remove the source of osteolysis (polyethylene) but cannot always remove all of the inflammatory granulomatous tissues in the joint. We used a human/rat xenograft model to evaluate the effects of polyethylene granuloma tissues on bone healing. Human osteoarthritic and periprosthetic tissues collected during primary and revision hip arthroplasty surgeries were transplanted into the distal femora of athymic (nude) rats. The tissues were assessed before and after implantation and the bone response to the tissues was evaluated after 1 week and 3 weeks using micro-computed tomography, histology, and immunohistochemistry. After 3 weeks, the majority (70%) of defects filled with osteoarthritic tissues healed, while only 21% of defects with polyethylene granuloma tissues healed. Polyethylene granuloma tissues in trabecular bone defects inhibited bone healing. Surgeons should remove polyethylene granuloma tissues during revision surgery when possible, since these tissues may slow bone healing around a newly implanted prosthesis. This model provides a method for delivering clinically relevant sized particles into an
This study evaluated the biologic fixation of two different titanium porous coatings: a clinically successful sintered spherical bead coating [ The time-zero average peak push-out load (±S.D.) of the STIKTITE group (95±3 N) was found to be significantly greater (p <
0.02) than that of the spherical bead group (36±5 N). By six weeks in vivo, the average peak push-out load for the STIKTITE group was up to 1001±362 N, and that for the spherical bead group was up to 985±425 N, both representing a significant increase compared to their time-zero results (p <
0.0005). From six to twenty-six weeks in vivo, there was again a significant increase in the peak push-out load irrespective of group (p <
0.0005), with the average peak push-out loads up to 1620±406 N and 1444±446 N for the STIK-TITE and spherical bead groups, respectively. Histology revealed bone ingrowth in both groups that confirmed the findings of the mechanical push-out testing. While the STIKTITE group showed a trend toward greater biologic fixation, overall there was insufficient evidence to support differences between the two groups (p = 0.47) irrespective of the amount of time in vivo. The results of this study confirm the ability of the STIK-TITE coating to achieve superior initial stability. This improved initial stability reduces the reliance on adjunct fixation (such as screws) or large amounts of press-fit to prevent micromotion and create an environment suitable for long-term bone ingrowth. The results also suggest that the STIKTITE coating had a tendency to initiate and maintain bone ingrowth under load-bearing conditions to a level greater than that of a clinically successful sintered bead coating. Because loading of the implant can cause micromotion at the bone/implant interface, models like the one used in this study likely provide a more challenging and realistic representation of anticipated clinical conditions than models with minimal implant loading.
We used demineralised bone matrix (DBM) to augment re-attachment of tendon to a metal prosthesis in an A significant increase of 23.5% was observed in functional weight-bearing at six weeks in the DBM-augmented group compared with non-augmented controls (p = 0.004). By 12 weeks augmentation with DBM resulted in regeneration of a more direct-type enthesis, with regions of fibrocartilage, mineralised fibrocartilage and bone. In the controls the interface was predominantly indirect, with the tendon attached to the bone graft-hydroxyapatite base plate by perforating collagen fibres.
INTRODUCTION: Intradiscal electrothermal therapy (IDET) is being used increasingly as a minimally-invasive treatment for chronic discogenic low back pain, with success reported in up to 70% of cases. The mechanism of action however is poorly understood. Proposed mechanisms include the contraction of collagen and the coagulation of annular nociceptors. An ovine model was used to assess the innervation of peripheral posterolateral annular lesions and the potential for IDET to denervate this region. METHODS: Posterolateral annular incisions were made in 36 lumbar discs of 18 sheep. After twelve weeks the sheep underwent IDET at one level and a sham treatment at the other level. IDET was performed using a modified intradiscal catheter (SpineCATHTM, Oratec Interventions Inc., Menlo Park, CA). Temperatures were recorded in the nucleus and the posterior annulus. The spines were harvested at intervals of up to eighteen months. Histological sections of the discs were stained with haematoxylin and eosin and an antibody to the general neuronal marker PGP 9.5. RESULTS: The target temperature of 90°C at the catheter tip was reached in all cases. The mean maximum TPa was 63.6°C and the mean maximum TN was 67.8°C. Vascular granulation tissue consistent with a healing response was observed in the region of the posterior annulus tear of all incised discs from 12 weeks. PGP 9.5 positive nerve fibres were clearly identified in the adjacent periannular tissue, but were scarce within the outer few lamellae of the annulus. There were no fewer nerve fibres identified in those specimens that had undergone IDET. From six weeks after IDET there was evidence of thermal necrosis in the inner annulus, sparing the periphery of the disc. DISCUSSION: IDET delivered at 90°C in the sheep consistently heats the posterior annulus and the nucleus to a temperature associated with coagulation of nociceptors and collagen contraction. Thermal necrosis was observed within the inner annulus from six weeks after IDET. In this model IDET did not appear to produce denervation of the posterior annular lesion.
We used an A significant improvement in functional weight-bearing was observed between six and 12 weeks. The significant increase in ground reaction force through the operated limb between six and 12 weeks was greater than that reported previously with morcellised graft augmented reconstructions. Histological appearance and collagen fibre orientation with bone block augmentation more closely resembled that of an intact enthesis compared with the morcellised grafting technique. Bone block augmentation of tendon-implant interfaces results in more reliable functional and histological outcomes, with a return to pre-operative levels of weight-bearing by 24 weeks.
Surgeons treating fractures with many small osteochondral fragments have often expressed the clinical need for an adhesive to join such fragments, as an adjunct to standard implants. If an adhesive would maintain alignment of the articular surfaces and subsequently heal it could result in improved clinical outcomes. However, there are no bone adhesives available for clinical indications and few pre-clinical models to assess safety and efficacy of adhesive biomaterial candidates. A bone adhesive candidate based on water, α-TCP and an amino acid phosphoserine was evaluated in-vivo in a novel murine bone core model (preliminary results presented EORS 2019) in which excised bone cores were glued back in place and harvested @ 0, 3, 7, 14, 28 and 42days. Adhesive pull-out strength was demonstrated 0–28 days, with a dip at 14 days increasing to 11.3N maximum. Histology 0–42 days showed the adhesive progressively remodelling to bone in both cancellous and cortical compartments with no signs of either undesirable inflammation or peripheral ectopic bone formation. These favourable results suggested translation to a large
There are concerns with regard to the physiological effects of reamed intramedullary femoral fracture stabilisation in patients who have received a pulmonary injury. This large animal study used invasive monitoring techniques to obtain sensitive cardiopulmonary measurements and compared the responses to Early Total Care (reamed intramedullary femoral fracture fixation) to Damage Control Orthopaedics (external fixation), after the induction of acute lung injury. We hypothesised a greater cardiopulmonary response to intramedullary fracture fixation. Acute lung injury (PaO2/FiO2 < 200 mmHg) was induced in 12 invasively monitored and terminally anaesthetised male sheep via the infusion of oleic acid into the right atrium. Each animal underwent surgical femoral osteotomy and fixation with either reamed intramedullary (n=6) or external fixation (n=6). Simultaneous haemodynamic and arterial blood-gas measurements were recorded at baseline and at 5, 30 and 60 minutes after fracture stabilisation.Purpose
Method
First described in 1910, Legg Calve Perthes disease is considered to be a complication of osteonecrosis of the femoral head-affecting children between the ages of 2 and 12. Treatment has centred on containment, surgical and non-surgical in the hope that keeping the femoral head covered by acetabulum that it will remodel and maintain congruency with the acetabulum. We know from previous studies that deformities of the femoral head increase the risk of development of arthritis in later life and that the shape of the femoral head is the only alterable parameter in the development of this early onset arthritis. During the natural history of the disease, once the central part of the femoral head collapses the integrity of the femoral head is reliant on the support of the lateral and medial columns. These columns then collapse altering the shape of the femoral head. We induced LCPD in the femoral heads of twenty skeletally immature rabbits and buttressed the central column of the femoral head in twelve. These treated rabbits had cement, bone graft or bone paste inserted through a drill hole that extended into the centre of the femoral head. The rabbits were then recovered and x-rayed at six weeks. All the rabbits had evidence of varying degrees of head collapse radiologically. Once the rabbits reach skeletal maturity in March, they will be euthanised and their femoral heads examined histologically and radiologically to determine the effects of central column enhancement by each of the three substances.
Aims. Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo
Introduction: The beneficial effects of insulin in the maintenance of normoglycaemia in non-diabetic myocardial infarct and intensive care patients have recently been reported. Hyperglycaemia and neutrophilia have been shown to be independent prognostic indicators of poor outcome in the traumatised patient. The role of insulin and the maintenance of normoglycaemia in the trauma patient have as yet not been explored. We hypothesised that through the already described anti-inflammatory effects of insulin and the maintenance of normoglycaemia, that the systemic inflammatory response would be attenuated, in the injured patient. This might result in less adult respiratory distress syndrome (ARDS) and multi-organ dysfunction and therefore less morbidity and mortality in trauma patients. Materials and Methods: We used a previously validated rodent trauma model. There were 3 groups, two groups underwent bilateral femur fracture and 15% blood loss via cannulation and aspiration of the external jugular vein. The third group were anaesthetised only. The treatment group immediately receive subcutaneous insulin according to a recently identified sliding scale, and thereafter subcutaneous boluses, dependent on ½ hourly blood sugar estimations. The control groups received the same volume of normal saline ½ hourly, subcutaneously. The animals were maintained under anaesthetic for 4 hours from injury via inhaled isoflurane and oxygen. Core temperature and O2 saturations were recorded throughout. At 4 hours, each animal underwent midline laparotomy and cannulation of the IVC for blood sampling for full blood counts and lactate levels. Serum was also taken for flow cytometric analysis of neutrophil activation via respiratoy burst and CD11b levels. Broncho-alveolar lavage (BAL) was performed for neutrophil content and total protein estimation. The left lower lobe was harvested for wet-dry lung weight ratios. Results: While O2 saturations were equal throughout in both groups, respiratory rates were persistently elevated in the controls. Wet:Dry lung weight ratios (p<
0.05) and lactate levels were reduced in the insulin treated animals compared to controls. There were similiarly fewer neutrophils in the BAL specimens of the insuliln treated animals compared to injured controls (p<
0.05). Conclusions: Insulin reduces leukocyte lung sequestration in the injured
Aims. As has been shown in larger
Mesenchymal stem-cell based therapies have been
proposed as novel treatments for intervertebral disc degeneration,
a prevalent and disabling condition associated with back pain. The
development of these treatment strategies, however, has been hindered
by the incomplete understanding of the human nucleus pulposus phenotype
and by an inaccurate interpretation and translation of animal to
human research. This review summarises recent work characterising
the nucleus pulposus phenotype in different
Due to well-known disadvantages of the autologous bone graft, many alternatives have been studied for a reliable spinal fusion. Herein, we aimed to investigate the effects of human recombinant epidermal growth factor (EGF) on posterolateral lumbar fusion in a rat model. 36 male SD rats underwent posterolateral fusion at L4-5 level. They were randomly assigned to 3 groups: Sham control group, Hydoxyapatite β-tricalcium phosphate (HA/β-TCP) group and HA/β-TCP + EGF group. Rats were euthanized at 8 weeks post-surgery. 6 rats from each group were selected for manual palpation examination, micro-computed tomography analysis and histologic analysis; and the rest was used for biomechanical analysis. Based on manual palpation, there was no fusion in the sham control group. Fusion rate was 33.3% in the HA/β-TCP group and 66.7% in the HA/β-TCP + EGF group (p=0.085). Micro-CT results revealed that new bone formation was higher in the HA/β-TCP + EGF group (BV/TV: 40% vs. 65%) (p=0.004). Histologically newly formed bone tissue was more pronounced in the EGF group and compacted and bridging bone spicules were observed. The median maximum bending moment values were 0.51 Nmm (0.42– 0.59), 0.73 Nmm (0.49– 0.88) and 0.91 Nmm (0.66– 1.03) in the sham control, HA/β-TCP and HA/β-TCP + EGF groups, respectively (p=0.013). The median stiffness values were 1.69 N/mm (1.12–2.18), 1.68 N/mm (1.13–2.74) and 3.10 N/mm (1.66–4.40) as in the previous order (p=0.087). This study demonstrates that EGF enhances posterolateral lumbar fusion in the rat model. EGF in combination with ceramic grafts increased the fusion rates.
Translational models for OA have used a variety of small (mouse, rat) and large (sheep, pig)
Osteoporosis is a progressive, chronic disease of bone metabolism, characterized by decreased bone mass and mineral density, predisposing individuals to an increased risk of fractures. The use of
Aims. To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model. Methods. A modularized experimental device has been developed that allows rat models to be used instead of large
To create a comprehensive, user-friendly, database that facilitates selection of optimized
Introduction. Major trauma during military conflicts involve heavily contaminated open fractures. Staphylococcus aureus (S. aureus) commonly causes infection within a protective biofilm. Lactoferrin (Lf), a natural milk glycoprotein, chelates iron and releases bacteria from biofilms, complimenting antibiotics. This research developed a periprosthetic biofilm infection model in rodents to test an Lf based lavage/sustained local release formulation embedded in Stimulin beads. Method. Surgery was performed on adult rats and received systemic Flucloxacillin (Flu). The craniomedial tibia was exposed, drilled, then inoculated with S. aureus biofilm. A metal pin was placed within the medullary cavity and treatments conducted. Lf in lavage solutions: The defect was subject to 2× 50 mL lavage with 4 treatment groups (saline only, Lf only, Bactisure with Lf, Bactisure with saline). Lf embedded in Stimulin beads: 4 bead types were introduced (Stimulin only, Lf only, Flu only, Lf with Flu). At day 7, rats are processed for bioluminescent and X-ray imaging, and tibial explants/pins collected for bacterial enumeration (CFU). Results. Rats without treatments established a mean infection of 2×106 CFU/tibia. 4 treatment groups with a day 0, one-off lavage demonstrated >95% reduction in bacterial load 7 days post-op, with a reduction in CFU from 1×106/tibia down to 1×104/tibia. There was no statistically significant difference between each group (p = 0.55 with one way ANOVA). The stimulin bead experiments are ongoing and complete results will be obtained in the end of July. Conclusions. This research demonstrated a clinically relevant
Prosthetic joint infection (PJI) is a complex disease that causes significant damage to the peri-implant tissue. Developing an
In this work, we propose a new quantitative way of evaluating acute compartment syndrome (ACS) by dynamic mechanical assessment of soft tissue changes. First, we have developed an
Aim. To provide proof of concept in an in vivo
Aim. Debridement, Antibiotics, Irrigation, and implant Retention (DAIR) is a surgical treatment protocol suitable for some patients with fracture related infection (FRI). Clinically relevant pre-clinical models of DAIR are scarce and none have been developed in large animals. Therefore, this project aimed to develop a large
Abstract. Objectives. Despite overwhelming need, with about 9 million osteoarthritis (OA) sufferers in UK alone, little progress has been made towards pathogenesis-based categorising of patients and subsequent intervention. Experimental studies relied heavily on
Aims. Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells. Methods. HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury
Abstract. Objectives. Tendon and ligament injury poses an increasingly large burden to society. With surgical repair and grafting susceptible to high failure rates, tissue engineering provides novel avenues for treatment. This systematic review explores in vivo evidence whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can facilitate tendon and ligament repair in
Aims. Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT
Aims. Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone. Methods. S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs). Results. Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms. Conclusion. Halicin is a promising antibiotic that should be tested in
Objectives. Recently, the field of tissue engineering has made numerous advances towards achieving artificial tendon substitutes with excellent mechanical and histological properties, and has had some promising experimental results. The purpose of this systematic review is to assess the efficacy of tissue engineering in the treatment of tendon injuries. Methods. We searched MEDLINE, Embase, and the Cochrane Library for the time period 1999 to 2016 for trials investigating tissue engineering used to improve tendon healing in
Aim. To conduct a systematic review of non-rodent
Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small
Abstract. Purpose. It is becoming apparent that mesenchymal stem cells (MSCs) do not directly contribute to mesenchymal tissue regeneration. Pre-clinical attempts to repair large bone defects in big
Aims. The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current
Objectives. This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling. Methods. A systematic search was performed in Pubmed, followed by a two-step selection process. We included in vivo original studies on Sr-containing biomaterials used for bone support or regeneration, comparing at least two groups that only differ in Sr addition in the experimental group. Results. A total of 572 references were retrieved and 27 were included.
No
In-vitro models of disease are valuable tools for studying disease and analysing response to therapeutics. Recently, advances in patient-derived organoid (PDO) models have been shown to faithfully recapitulate structure, function, and therapeutic response for a wide range of tissues. Frozen shoulder is a rare example of a chronic inflammatory fibrotic disease which is self-limiting, unlike many other soft tissue fibrotic disorders. As no in-vitro 3D models or in-vivo
Aims. Periprosthetic joint infections (PJIs) and osteomyelitis are clinical challenges that are difficult to eradicate. Well-characterized large
Tryfonidou leads the Horizon 2020 consortium (iPSpine; 2019–2023) bringing a transdisciplinary team of 21 partners together to address the challenges and bottlenecks of iPS-based advanced therapies towards their transition to the clinic. Here, chronic back pain due to intervertebral disc degeneration is employed as a show case. The project develops the iPS-technology and designed smart biomaterials to carry, protect and instruct the iPS cells within the degenerate disc environment. This work will be presented including ongoing activities focus on translating the developed methodology and tools towards clinically relevant
Objective . Dunkin Hartley guinea pigs, a commonly used
Aims. Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. Methods. OA
Device-associated bacterial infections are a major and costly clinical challenge. This project aimed to develop a smart new biomaterial for implants that helps to protect against infection and inflammation, promote bone growth, and is biodegradable. Gallium (Ga) doped strontium-phosphate was coated on pure Magnesium (Mg) through a chemical conversion process. Mg was distributed in a graduated manner throughout the strontium-phosphate coating GaSrPO4, with a compact structure and a Ga-rich surface. We tested this sample for its biocompatibility, effects on bone remodeling and antibacterial activities including Staphylococcus aureus, S. epidermidis and E. coli - key strains causing infection and early failure of the surgical implantations in orthopaedics and trauma. Ga was distributed in a gradient way throughout the entire strontium-phosphate coating with a compact structure and a gallium-rich surface. The GaSrPO4 coating protected the underlying Mg from substantial degradation in minimal essential media at physiological conditions over 9 days. The liberated Ga ions from the coatings upon Mg specimens inhibited the growth of bacterial tested. The Ga dopants showed minimal interferences with the SrPO4 based coating, which boosted osteoblasts and undermined osteoclasts in in vitro co-cultures model. The results evidenced this new material may be further translated to preclinical trial in large
Aims. Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant
Osteosarcoma is common in children and adolescents with high mortality due to rapid progression. Therapeutic approaches for osteosarcoma are limited and may cause side effects. Cannabinoid ligands exert antiproliferative, apoptotic effect in cancer cells via CB1/2 or TRPV1 receptors. In this study, we hypothesized that synthetic specific CB2R agonist CB65 might have an antiproliferative and apoptotic effect on osteosarcoma cell lines in vitro. If so, this agent might be a chemotherapeutic candidate for osteosarcoma, with prolonged release, increased stability and bioavailability when loaded into a liposomal system. We first determined CB2 receptor expression in MG63 and Saos-2 osteosarcoma cells by qRT- PCR and FCM. CB65 reduced proliferation in osteosarcoma cells by WST-1 and RTCA. IC50 for MG63 and Saos-2 cells were calculated as 1.11×10-11 and 4.95×10-11 M, respectively. The antiproliferative effect of CB65 on osteosarcoma cells was inhibited by CB2 antagonist AM630. IC50 of CB65 induced late apoptosis of MG63 and Saos-2 cells at 24 and 48 hours, respectively by FCM. CB65 was loaded into the liposomal system by thin film hydration method and particle size, polydispersity index, and zeta potentials were 141.7±0.6 nm, 0.451±0.026, and -10.9±0.3 mV, respectively. The CB65-loaded liposomal formulation reduced MG63 and Saos-2 cell proliferation by RTCA. IC50 of CB65 and CB65-loaded liposomal formulation induced late apoptosis of MG63 and Saos-2 cells at 24 and 48 hours, respectively, by FCM. Scratch width was higher in CB65 and CB65-loaded liposome-treated cells compared to control. In this study, the real-time antiproliferative and apoptotic effect of synthetic specific CB2 agonist CB65 in osteosarcoma cell lines was demonstrated for the first time, and the real time therapeutic window was determined. The CB65-loaded liposomal formulation presents a potential treatment option that can be translated to clinic following its validation within
The fixation of articular fractures, with many small osteochondral fragments, is a challenging unmet need where a bone adhesive would be a useful adjunct to standard treatments. Whilst there are no such adhesives in current clinical use, preclinical
Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. To date, there are no
Restoration a joint's articular surface following degenerative or traumatic pathology to the osteochondral unit pose a significant challenge. Recent advances have shown the utility of collagen-based scaffolds in the regeneration of osteochondral tissue. To provide these collagen scaffolds with the appropriate superstructure novel techniques in 3D printing have been investigated. This study investigates the use of polyɛ-caprolactone (PCL) collagen scaffolds in a porcine cadaveric model to establish the stability of the biomaterial once implanted. This study was performed in a porcine cadaveric knee model. 8mm defects were created in the medial femoral trochlea and repaired with a PCL collagen scaffold. Scaffolds were secured by one of three designs; Press Fit (PF), Press Fit with Rings (PFR), Press Fit with Fibrin Glue (PFFG). Mobilisation was simulated by mounting the pig legs on a continuous passive motion (CPM) machine for either 50 or 500 cycles. Biomechanical tensile testing was performed to examine the force required to displace the scaffold. 18 legs were used (6 PF, 6 PFR, 6 PFFG). Fixation remained intact in 17 of the cohort (94%). None of the PF or PFFG scaffolds displaced after CPM cycling. Mean peak forces required to displace the scaffold were highest in the PFFG group (3.173 Newtons, Standard deviation = 1.392N). The lowest peak forces were observed in the PFR group (0.871N, SD = 0.412N), while mean peak force observed in the PF group was 2.436N (SD = 0.768). There was a significant difference between PFFG and PFR (p = 0.005). There was no statistical significance in the relationship between the other groups. PCL reinforcement of collagen scaffolds provide an innovative solution for improving stiffness of the construct, allowing easier handling for the surgeon. Increasing the stiffness of the scaffold also allows press fit solutions for reliable fixation. Press fit PCL collagen scaffolds with and without fibrin glue provide dependable stability. Tensile testing provides an objective analysis of scaffold fixation. Further investigation of PCL collagen scaffolds in a live
Surgical reattachment of torn rotator cuff tendons can lead to satisfactory clinical outcome but failures remain common. Ortho-R product is a freeze-dried formulation of chitosan (CS) that is solubilized in platelet-rich plasma (PRP) to form injectable implants. The purpose of the current pilot study was to determine Ortho-R implant acute residency, test safety of different implant doses, and assess efficacy over standard of care in a sheep model. The infraspinatus tendon (ISP) was detached and immediately repaired in 22 skeletally mature ewes. Repair was done with four suture anchors in a suture bridge configuration (n = 6 controls). Freeze-dried formulations containing 1% w/v chitosan (number average molar mass 35 kDa and degree of deacetylation 83%) with 1% w/v trehalose (as lyoprotectant) and 42.2 mM calcium chloride (as clot activator) were solubilized with autologous leukocyte-rich PRP and injected at the tendon-bone interface and on top of the repaired site (n = 6 with a 1 mL dose and n = 6 with a 2 mL dose). Acute implant residency was assessed histologically at 1 day (n = 2 with a 1 mL dose and n = 2 with a 2 mL dose). Outcome measures included MRI assessment at baseline, 6 weeks and 12 weeks, histopathology at 12 weeks and clinical pathology. MRI images and histological slides were scored by 2 blinded readers (veterinarian and human radiologist, and veterinarian pathologist) and averaged. The Generalized Linear Model task (SAS Enterprise Guide 7.1 and SAS 9.4) was used to compare the different groups with post-hoc analysis to test for pairwise differences. Ortho-R implants were detected near the enthesis, near the top of the anchors holes and at the surface of ISP tendon and muscle at 1 day. Numerous polymorphonuclear cells were recruited to the implant in the case of ISP tendon and muscle. On MRI, all repair sites were hyperintense compared to normal tendon at 6 weeks and only 1 out 18 repair sites was isointense at 12 weeks. The tendon repair site gap seen on MRI, which is the length of the hyperintense region between the greater tuberosity and tendon with normal signal intensity, was decreased by treatment with the 2 mL dose when compared to control at 12 weeks (p = 0.01). Histologically, none of the repair sites were structurally normal. A trend of improved structural organization of the tendon (p = 0.06) and improved structural appearance of the enthesis (p = 0.1) with 2 mL dose treatment compared to control was seen at 12 weeks. There was no treatment-specific effect on all standard safety outcome measures, which suggests high safety. Ortho-R implants (2 mL dose) modulated the rotator cuff healing processes in this large
Recent studies on
In the past decades, a huge amount of effort has been devoted to translate evidence based on standard preclinical models of bone tumours to effective tools for clinical applications. Although cancer is a genetic disease, hence the emphasis on -omics approaches, the complexity of cancer tissue, a mix of competing clones of transformed elements that react differently to microenvironmental stimuli, may hardly be reproduced by standard approaches. Cost, biological differences and ethical concerns are increasingly recognized as weaknessess of
Bone allograft is the most widely accepted approach in treating patients suffering from large segmental bone defect regardless of the advancement of synthetic bone substitutes. However, the long-term complications of allograft application in term of delayed union and nonunion were reported due to the stringent sterilization process. Our previous studies demonstrated that the incorporation of magnesium ions (Mg2+) into biomaterials could significantly promote the gene up-regulation of osteoblasts and new bone formation in
Carpal tunnel syndrome (CTS) is the most common condition affecting the hand, with a prevalence of 2–3% in most populations, and a lifetime incidence over 10%. There is consensus that CTS results from increased pressure in the carpal tunnel, which eventually affects nerve function, but, aside from direct trauma and space occupying lesions, there is no consensus on what causes the pressure to rise. In the absence of an identifiable biological mechanism, the most common treatment involves surgical opening of the carpal tunnel. Recent data suggests that CTS patients demonstrate, in the carpal tunnel synovium and subsynovial connective tissue (SSCT), evidence of cellular senescence, with a senescence associated secretory phenotype (SASP). This finding suggests the potential for a biological treatment for CTS with senolytic drugs. This presentation will review the evidence for CTS as a disease of cellular senescence, and our preliminary data on the effects of senolytics, including in a relevant
Osteoarthritis (OA) is the most prevalent degenerative joint disease that is a leading cause of disability worldwide. Existing therapies of OA only address the symptoms. Liraglutide is a well-known anti-diabetic medication that is used to treat type 2 diabetes and obesity. In inflammatory and post-traumatic OA
Segmental bone transport (SBT) with an external fixator has become a standard method for treatment of large bone defect. However, a long time-application of devices can be very troublesome and complications such as nonunion is sometimes seen at docking site. Although there have been several studies on SBT with large
Bone non-union following fracture is a major cause of morbidity in combat casualties. The various clinical treatments used to prevent or treat non-union remain of limited efficacy. Research therefore continues in pre-clinical
Aims. Femoral bone preparation using compaction technique has been shown to preserve bone and improve implant fixation in