This review is aimed at clinicians appraising preclinical trauma studies and researchers investigating compromised bone healing or novel treatments for fractures. It categorises the clinical scenarios of poor healing of fractures and attempts to match them with the appropriate animal models in the literature.

We performed an extensive literature search of animal models of long bone fracture repair/nonunion and grouped the resulting studies according to the clinical scenario they were attempting to reflect; we then scrutinised them for their reliability and accuracy in reproducing that clinical scenario.

Models for normal fracture repair (primary and secondary), delayed union, nonunion (atrophic and hypertrophic), segmental defects and fractures at risk of impaired healing were identified. Their accuracy in reflecting the clinical scenario ranged greatly and the reliability of reproducing the scenario ranged from 100% to 40%.

It is vital to know the limitations and success of each model when considering its application.

Four uncemented Symax hip stems were extracted at three weeks and nine, 13 and 32 months, respectively, for reasons other than loosening. The reasons for implant removal were infection in two cases, recurrent dislocation in one and acetabular fracture in one. They were analysed to assess the effect and behaviour of an electrochemically deposited, completely resorbable biomimetic BONIT-hydroxyapatite (HA) coating (proximal part) and a DOTIZE surface treatment (distal part) using qualitative histology, quantitative histomorphometry and scanning electron microscopy (SEM). Early and direct bone-implant bonding with signs of active remodelling of bone and the HA coating were demonstrated by histology and SEM. No loose BONIT-HA particles or delamination of the coating were observed, and there was no inflammation or fibrous interposition at the interface.

Histomorphometry showed bone-implant contact varying between 26.5% at three weeks and 83.5% at 13 months at the HA-coated implant surface. The bone density in the area of investigation was between 24.6% at three weeks and 41.1% at 32 months. The DOTIZE surface treatment of the distal part of the stem completely prevented tissue and bone apposition in all cases, thereby optimising proximal stress transfer.

The overall features of this implant, in terms of geometry and surface texture, suggest a mechanically stable design with a highly active biomimetic coating, resulting in rapid and extensive osseo-integration, exclusively in the metaphyseal part of the stem. Early remodelling of the HA coating does not seem to have a detrimental effect on short-term bone-implant coupling. There were no adverse effects identified from either the BONIT-HA coating or the DOTIZE surface treatment.

We have investigated the effectiveness of the transplantation of bone-marrow-derived mononuclear cells (BMMNCs) with interconnected porous calcium hydroxyapatite (IP-CHA) on early bone repair for osteonecrosis of the femoral head. We studied 22 patients (30 hips) who had osteonecrosis with a minimum follow-up of one year after implantation of BMMNCs. The mean age at surgery was 41 years (18 to 64) and the mean period of follow-up was 29 months (19 to 48). In a control group, cell-free IP-CHA was implanted into a further eight patients (9 hips) with osteonecrosis of the femoral head and the outcomes were compared.

A reduction in the size of the osteonecrotic lesion was observed subsequent to hypertrophy of the bone in the transition zone in the BMMNC group. In three patients in the treatment group progression to extensive collapse was detected. In the control group subtle bone hypertrophy was observed, but severe collapse of the femoral head occurred in six of eight hips.

In this limited study the implantation of BMMNCs and IP-CHA appears to confer benefit in the repair of osteonecrosis and in the prevention of collapse.

We used interconnected porous calcium hydroxyapatite ceramic to bridge a rabbit ulnar defect. Two weeks after inducing the defect we percutaneously injected rabbit bone marrow-derived mesenchymal stromal cells labelled with ferumoxide. The contribution of an external magnetic targeting system to attract these cells into the ceramic and their effect on subsequent bone formation were evaluated.

This technique significantly facilitated the infiltration of ferumoxide-labelled cells into ceramic and significantly contributed to the enhancement of bone formation even in the chronic phase. As such, it is potentially of clinical use to treat fractures, bone defects, delayed union and nonunion.

We describe the treatment by subperiosteal resection of an aneurysmal bone cyst in the distal fibula in eight patients and highlight the role of the periosteum in the regeneration of bone defects. The mean age of the patients was 13.5 years (12 to 17). Seven had an open growth plate. The mean size of the resected specimen was 5.12 cm (3.5 to 8.0). None of the patients received instillation of bone marrow, autogenous bone graft, allograft or any synthetic bone substitutes.

All had complete regeneration of the bone defect within three to nine months, with no joint instability or recurrence.

The mean length of follow-up was 11.5 years (2 to 18). At the final follow-up there was no difference in the range of movement, alignment or stability of the ankle when compared with the opposite side. The periosteum played a major role in the complete filling of the bone defects and avoided the morbidity of other techniques.

We used demineralised bone matrix (DBM) to augment re-attachment of tendon to a metal prosthesis in an in vivo ovine model of reconstruction of the extensor mechanism at the knee. We hypothesised that augmentation of the tendon-implant interface with DBM would enhance the functional and histological outcomes as compared with previously reported control reconstructions without DBM. Function was assessed at six and 12 weeks postoperatively, and histological examination was undertaken at 12 weeks.

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.

Wear of polyethylene is associated with aseptic loosening of orthopaedic implants and has been observed in hip and knee prostheses and anatomical implants for the shoulder. The reversed shoulder prostheses have not been assessed as yet. We investigated the volumetric polyethylene wear of the reversed and anatomical Aequalis shoulder prostheses using a mathematical musculoskeletal model. Movement and joint stability were achieved by EMG-controlled activation of the muscles. A non-constant wear factor was considered. Simulated activities of daily living were estimated from in vivo recorded data.

After one year of use, the volumetric wear was 8.4 mm³ for the anatomical prosthesis, but 44.6 mm³ for the reversed version. For the anatomical prosthesis the predictions for contact pressure and wear were consistent with biomechanical and clinical data. The abrasive wear of the polyethylene in reversed prostheses should not be underestimated, and further analysis, both experimental and clinical, is required.

In order to investigate the osteoinductive properties of allograft used in impaction grafting and the effect of strain during impaction on these properties, we designed an in vitro experiment to measure strain-related release of bone morphogenetic protein-7 (BMP-7) from fresh-frozen femoral head allograft. A total of 40 10 mm cubes of cancellous bone were cut from ten samples of fresh-frozen femoral head. The marrow was removed from the cubes and the baseline concentrations of BMP-7 were measured. Specimens from each femoral head were allocated to four groups and subjected to different compressive strains with a material testing machine, after which BMP-7 activity was reassessed. It was present in all groups. There was a linear increase of 102.1 pg/g (95% confidence interval 68.6 to 135.6) BMP-7 for each 10% increase in strain. At 80% strain the mean concentration of BMP-7 released (830.3 pg/g bone) was approximately four times that released at 20% strain. Activity of BMP-7 in fresh-frozen allograft has not previously been demonstrated. This study shows that the freezing and storage of femoral heads allows some maintenance of biological activity, and that impaction grafting provides a source of osteoinductive bone for remodelling.

We have shown that BMP-7 is released from fresh-frozen femoral head cancellous bone in proportion to the strain applied to the bone. This suggests that the impaction process itself may contribute to the biological process of remodelling and bony incorporation.

The management of osteonecrosis of the femoral head ranges from symptomatic therapy to total hip replacement. Conservative treatment is effective only in small, early-stage lesions. Free vascularised fibular grafting has provided more consistently successful results than any other joint-preserving method. It supports the collapsing subchondral plate by primary callus formation, reduces intra-osseous pressure, removes and replaces the necrotic segment, and adds viable cortical bone graft plus fresh cancellous graft, which has osseoinductive and osseoconductive potential. Factors predisposing to success are the aetiology, stage and size of the lesion. Furthermore, it is a hip-salvaging procedure in early pre-collapse stages, and a time-buying one when the femoral head has collapsed.

We examined cultured osteoblasts derived from paired samples from the greater tuberosity and acromion from eight patients with large chronic tears of the rotator cuff.

We found that osteoblasts from the tuberosity had no apparent response to mechanical stimulation, whereas those derived from the acromion showed an increase in alkaline phosphatase activity and nitric oxide release which is normally a response of bone cells to mechanical strain. By contrast, we found that cells from both regions were able to respond to dexamethasone, a well-established promoter of osteoblastic differentiation, with the expected increase in alkaline phosphatase activity.

Our findings indicate that the failure of repair of the rotator cuff may be due, at least in part, to a compromised capacity for mechanoadaptation within the greater tuberosity. It remains to be seen whether this apparent decrease in the sensitivity of bone cells to mechanical stimulation is the specific consequence of the reduced load-bearing history of the greater tuberosity in these patients.

The management of bone loss in revision replacement of the knee remains a challenge despite an array of options available to the surgeon. Bone loss may occur as a result of the original disease, the design of the prosthesis, the mechanism of failure or technical error at initial surgery. The aim of revision surgery is to relieve pain and improve function while addressing the mechanism of failure in order to reconstruct a stable platform with transfer of load to the host bone. Methods of reconstruction include the use of cement, modular metal augmentation of prostheses, custom-made, tumour-type or hinged implants and bone grafting.

The published results of the surgical techniques are summarised and a guide for the management of bone defects in revision surgery of the knee is presented.

We analysed the operative technique, morbidity and functional outcome of osteotomy and plate fixation for malunited fractures of the forearm sustained in childhood.

A total of 20 consecutive patients underwent corrective osteotomy of 21 malunited fractures at a mean age of 12 years (4 to 25). The mean time between the injury and the osteotomy was 30 months (2 to 140).

After removal of the plate, one patient suffered transient dysaesthesia of the superficial radial nerve. The mean gain in the range of movement was 85° (20° to 140°). The interval between injury and osteotomy, and the age at osteotomy significantly influenced the functional outcome (p = 0.011 and p = 0.004, respectively).

Malunited fractures of the forearm sustained in childhood can be adequately treated by osteotomy and plate fixation with excellent functional results and minimal complications. In the case of established malunion it is advisable to perform corrective osteotomy without delay.

Deficiencies of acetabular bone stock at revision hip replacement were reconstructed with two different types of allograft using impaction bone grafting and a Burch-Schneider reinforcement ring. We compared a standard frozen non-irradiated bone bank allograft (group A) with a freeze-dried irradiated bone allograft, vitalised with autologous marrow (group B). We studied 78 patients (79 hips), of whom 87% (69 hips) had type III acetabular defects according to the American Academy of Orthopaedic Surgeons classification at a mean of 31.4 months (14 to 51) after surgery. At the latest follow-up, the mean Harris hip score was 69.9 points (13.5 to 97.1) in group A and 71.0 points (11.5 to 96.5) in group B. Each hip showed evidence of trabeculation and incorporation of the allograft with no acetabular loosening.

These results suggest that the use of an acetabular reinforcement ring and a living composite of sterile allograft and autologous marrow appears to be a method of reconstructing acetabular deficiencies which gives comparable results to current forms of treatment.

We present a series of 16 patients treated between 1993 and 2006 who had a failed total ankle replacement converted to an arthrodesis using bone grafting with internal fixation. We used tricortical autograft from the iliac crest to preserve the height of the ankle, the malleoli and the subtalar joint. A successful arthrodesis was achieved at a mean of three months (1.5 to 4.5) in all patients except one, with rheumatoid arthritis and severe bone loss, who developed a nonunion and required further fixation with an intramedullary nail at one year after surgery, before obtaining satisfactory fusion. The post-operative American Orthopaedic Foot and Ankle Society score improved to a mean of 70 (41 to 87) with good patient satisfaction. From this series and an extensive review of the literature we have found that rates of fusion after failed total ankle replacement in patients with degenerative arthritis are high. We recommend our method of arthrodesis in this group of patients. A higher rate of nonunion is associated with rheumatoid arthritis which should be treated differently.

We investigated the effect of locally administered bisphosphonate on distraction osteogenesis in a rabbit model and evaluated its systemic effect. An osteotomy on the right tibia followed by distraction for four weeks was performed on 47 immature rabbits. They were divided into seven equal groups, with each group receiving a different treatment regime. Saline and three types of dosage of alendronate (low, 0.75 μg/kg; mid, 7.5 μg/kg and high 75 μg/kg) were given by systemic injection in four groups, and saline and two dosages (low and mild) were delivered by local injection to the distraction gap in the remaining three groups. The injections were performed five times weekly during the period of distraction.

After nine weeks the animals were killed and image analysis and mechanical testing were performed on the distracted right tibiae and the left tibiae which served as a control group. The local low-dose alendronate group showed a mean increase in bone mineral density of 124.3 mg/cm³ over the local saline group (analysis of variance, p < 0.05) without any adverse effect on the left control tibiae.

The findings indicate that the administration of local low-dose alendronate could be an effective pharmacological means of improving bone formation in distraction osteogenesis.

We present a retrospective study of 27 patients treated by callus distraction using a unilateral external fixator of our own design for nonunion with bone loss and shortening of the femur caused by suppurative osteomyelitis. The unilateral external fixator was used either alone or in combination with an intramedullary nail. The mean age of the patients was 13.6 years (8 to 18). The fixator was used alone in 13 patients and with an intramedullary nail in 14. The bone results at a mean follow-up of 88 months (37 to 144) were excellent in 16 patients and good in 11.

The functional results were excellent in 18 patients and good in nine. However, four patients still had draining sinuses at the latest follow-up. A residual deformity greater than 7° was present in seven femora, but this did not adversely affect function or require further treatment.

Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet α granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-β, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches.

The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research.

The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats.

Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group.

Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function.