Objectives. The primary purpose of this meta-analysis was to determine whether statin usage could reduce the risk of glucocorticoid-related osteonecrosis in
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. 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
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
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
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.