Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice.

Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1⁺) and stem cell factor receptor, CD117 (c-kit⁺) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1⁺ mononuclear cell (MNC^sca-1+) populations were then cultured and examined for functional vascular endothelial differentiation. Bone marrow MNC^{sca-1+,c-kit+} counts increased almost twofold within 48 hours of the event, compared with baseline levels, before decreasing by 72 hours.

Sca-1⁺ mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1′-dioctadecyl- 3,3,3,’3′-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium.

Our findings suggest that a systemic provascular response of bone marrow is initiated by musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of neovascularisation and the healing of fractures.

Avascular necrosis of the femoral head creates considerable morbidity in successful renal transplant recipients who are generally young and expect active lifestyles. Total hip replacement is considered the treatment of choice in these patients, but surgeons may be wary because of a supposed increase in the risk of infection and other complications.

A review of the literature reveals that cemented hip arthroplasty provides good to excellent functional outcomes for renal transplant patients. Most authors have found that the risk of infection is not increased despite chronic immunosuppression, but the rates of general complications are and should be anticipated and treated. There is a high rate of early failure in these patients because of their young age and diffuse osteopenia as a result of secondary hyperparathyroidism related to the underlying renal disease and chronic steroid use. Recent studies have found that despite decreased bone stock in these patients, porous-coated prostheses are not contraindicated.

We have undertaken a prospective study in patients with a fracture of the femoral shaft requiring intramedullary nailing to test the hypothesis that the femoral canal could be a potential source of the second hit phenomenon. We determined the local femoral intramedullary and peripheral release of interleukin-6 (IL-6) after fracture and subsequent intramedullary reaming.

In all patients, the fracture caused a significant increase in the local femoral concentrations of IL-6 compared to a femoral control group. The concentration of IL-6 in the local femoral environment was significantly higher than in the patients own matched blood samples from their peripheral circulation. The magnitude of the local femoral release of IL-6 after femoral fracture was independent of the injury severity score and whether the fracture was closed or open.

In patients who underwent intramedullary reaming of the femoral canal a further significant local release of IL-6 was demonstrated, providing evidence that intramedullary reaming can cause a significant local inflammatory reaction.

We prospectively reviewed 1000 consecutive patients who underwent a cementless, hydroxyapatite-coated, stemless, total knee replacement over a period of nine years. Regular post-operative clinical follow-up was performed using the Knee Society score. The mean pre-operative score was 96, improving to 182 and 180 at five and ten years, respectively. To date, there have been seven (0.5%) cases which required revision, primarily for septic loosening (four cases), with low rates of other post-operative complications. The cumulative survival at ten years with revision as the end-point, was 99.14% (95% confidence interval 92.5 to 99.8). These results support the use of hydroxyapatite in a cementless total knee replacement since it can give reliable fixation with an excellent clinical and functional outcome.

Despite advances in the prevention and treatment of osteoporotic fractures, their prevalence continues to increase. Their operative treatment remains a challenge for the surgeon, often with unpredictable outcomes. This review highlights the current aspects of management of these fractures and focuses on advances in implant design and surgical technique.

We attempted to repair full-thickness defects in the articular cartilage of the trochlear groove of the femur in 30 rabbit knee joints using allogenic cultured chondrocytes embedded in a collagen gel. The repaired tissues were examined at 2, 4, 8, 12 and 24 weeks after operation using histological and histochemical methods. The articular defect filling index measurement was derived from safranin-O stained sections. Apoptotic cellular fractions were derived from analysis of apoptosis in situ using TUNEL staining, and was confirmed using caspase-3 staining along with quantification of the total cellularity. The mean articular defect filling index decreased with time. After 24 weeks it was 0.7 (sd 0.10), which was significantly lower than the measurements obtained earlier (p < 0.01). The highest mean percentage of apoptotic cells were observed at 12 weeks, although the total cellularity decreased with time. Because apoptotic cell death may play a role in delamination after chondrocyte transplantation, anti-apoptotic gene therapy may protect transplanted chondrocytes from apoptosis.

We evaluated 31 patients who were treated with a non-vascularised fibular graft after resection of primary musculoskeletal tumours, with a median follow-up of 5.6 years (3 to 26.7 years). Primary union was achieved in 89% (41 of 46) of the grafts in a median period of 24 weeks. All 25 grafts in 18 patients without additional chemotheraphy and/or radiotherapy achieved primary union, compared with 16 of the 21 grafts (76%; 13 patients) with additional therapy (p = 0.017). Radiographs showed an increase in diameter in 70% (59) of the grafts. There were seven fatigue fractures in six patients, but only two needed treatment.

Non-vascularised fibular transfer is a simpler, less expensive and a shorter procedure than the use of vascularised grafts and allows remodelling of the fibula at the donor site. It is a biological reconstruction with good long-term results, and a relatively low donor site complication rate of 16%.

The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis.

We developed an in vivo model of the attachment of a patellar tendon to a metal implant to simulate the reconstruction of an extensor mechanism after replacement of the proximal tibia. In 24 ewes, the patellar tendon was attached to a hydroxyapatite (HA)-coated titanium prosthesis. In 12, the interface was augmented with autograft containing cancellous bone and marrow. In the remaining ewes, the interface was not grafted.

Kinematic gait analysis showed nearly normal function of the joint by 12 weeks. Force-plate assessment showed a significant increase in functional weight-bearing in the grafted animals (p = 0.043). The tendon-implant interface showed that without graft, encapsulation of fibrous tissue occurred. With autograft, a developing tendon-bone-HA-implant interface was observed at six weeks and by 12 weeks a layered tendon-fibrocartilage-bone interface was seen which was similar to a direct-type enthesis.

With stable mechanical fixation, an appropriate bioactive surface and biological augmentation the development of a functional tendon-implant interface can be achieved.

The reduced stability of hydroxyapatite (HA)-coated implants in osteopenic conditions is considered to be a major problem. We therefore developed a model of a boosted cementless implantation in osteopenic rats.

Twelve-week-old rats were either ovariectomised (OVX) or sham-operated (SO), and after 24 weeks plain or HA-coated implants were inserted. They were treated with either a prostaglandin EP4 receptor agonist (ONO-4819) or saline for one month.

The EP4 agonist considerably improved the osteoporosis in the OVX group. Ultrastructural analysis and mechanical testing showed an improvement in the implant-bone attachment in the HA-coated implants, which was further enhanced by the EP4 agonist. Although the stability of the HA-coated implants in the saline-treated OVX rats was less than in the SO normal rats, the administration of the EP4 agonist significantly compensated for this shortage. Our results showed that the osteogenic effect of the EP4 agonist augmented the osteoconductivity of HA and significantly improved the stability of the implant-bone attachment in the osteoporotic rat model.

This retrospective study describes the long-term results of core decompression and placement of a non-vascularised bone graft in the management of avascular necrosis of the femoral head. We treated 80 hips in 65 patients, 18 by a cortical tibial autograft and 62 by a fibular allograft. The mean age of the patients was 36 years (sd 13.2). A total of 78 hips were available for evaluation of which pre-operatively six were Ficat-Arlet stage 0, three stage I, 31 stage IIA, 16 stage IIB, 13 stage III and nine stage IV.

A total of 34 hips (44%) were revised at a mean of four years (sd 3.8). Survivorship analysis using a clinical end-point showed a survival rate of 59% five years after surgery. We found a significant difference (p = 0.002) in survivorship, when using a clinical and radiological end-point, between the two grafts, in favour of the tibial autograft. We considered this difference to be the result of the better quality and increased volume of tibial bone compared with that from the trochanteric region used with the fibular allograft.

This is a relatively simple, extra-articular and reproducible procedure. In our view core decompression, removal of the necrotic tissue and packing of the cancellous grafts into the core track are vital parts of the procedure.

Bone allografts can store and release high levels of vancomycin. We present our results of a two-stage treatment for infected hip arthroplasty with acetabular and femoral impaction grafting using vancomycin-loaded allografts. We treated 29 patients (30 hips) by removal of the implants, meticulous debridement, parenteral antibiotic therapy and second-stage reconstruction using vancomycin-supplemented impacted bone allografts and a standard cemented Charnley femoral component. The mean follow-up was 32.4 months (24 to 60). Infection control was obtained in 29 cases (re-infection rate of 3.3%; 95% confidence interval 0.08 to 17) without evidence of progressive radiolucent lines, demarcation or graft resorption. One patient had a further infection ten months after revision caused by a different pathogen. Associated post-operative complications were one traumatic periprosthetic fracture at 14 months, a single dislocation in two hips and four displacements of the greater trochanter. Vancomycin-supplemented allografts restored bone stock and provided sound fixation with a low incidence of further infection.

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures.

Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility.