Aim. Antibiotic-loaded biomaterials are often used in dead space management after excision of infected bone. This study assessed the chronological progression of new bone formation in infected defects, filled only with an absorbable, osteoconductive bone void filler with Gentamicin (1). Method. 163 patients were treated for osteomyelitis or infected fractures with a single-stage excision, implantation of antibiotic carrier, stabilisation and wound closure. All had Cierny & Mader Type III (n=128) or Type IV (n=35) infection. No bone grafting was performed in any patient. Patients were followed up for a minimum of 12 months (mean 21.4 months; 12–56). Bone void filling was assessed on serial digitised, standardized radiographs taken immediately after surgery, at 6 weeks, 3, 6 and 12 months and then yearly. Data on defect size, location, degree of void filling, quality of the bone-biomaterial interface and material leakage were collected. Bone formation was calculated at final follow-up, as a percentage of initial defect volume, by determining the bone area on AP and lateral radiographs to the nearest 5%. Results. 138 patients had adequate radiographs for assessment. Infection was eradicated in 95.7%. 2.5% of patients suffered a fracture during follow-up. Overall, bone formation was good (mean 73.8% defect filling), with one quarter of patients having complete defect filling and 87% having more than 50% of the defect healed. Bone formed better in metaphyseal defects compared to diaphyseal defects (mean 79% filling vs 66%; p<0.02). Good interdigitation of the biomaterial with the host bone, seen on the initial radiograph, was associated with more bone formation (77% vs 69%; p=0.021). Leakage of the biomaterial out of the defect reduced mean bone formation from 77% to 62% (p=0.006). 38 cases had radiographs more than 2 years after implantation. In 24 (63.2%), bone formation continued to increase after the first year radiograph. Conclusion. This biomaterial was effective in allowing significant amounts of bone to form in the defect. This removed the need for bone grafting in this series, with a low risk of fracture or recurrent infection. However, bone formation is affected by the site of the lesion and the adequacy of filling at surgery. It is important to achieve good contact between the bone surface and the biomaterial at operation. Bone formation is slow and progresses for at least 2 years after implantation, in two thirds of patients

Purpose. Traditionally, the gold standard for bone grafting has been either autografts or allografts. Whilst autografts are still widely used, drawbacks such as donor site morbidity are shifting the market rapidly toward the use of orthobiologic bone graft substitutes. This study investigated the in vivo performance of a novel (W02008096334) collagen-hydroxyapatite (CHA) bone graft substitute material as an osteoinductive tissue engineering scaffold. This highly porous CHA scaffold offers significantly increased mechanical strength over collagen-only scaffolds while still exhibiting an extremely high porosity (≈ 99%), and an osteoinductive hydroxyapatite phase [1]. This study assessed the ability of the CHA scaffolds to heal critical-sized (15 mm) long bone segmental defects in vivo, as a viable alternative to autologous bone grafts. Method. Collagen-HA (CHA) composite scaffolds were fabricated based on a previously-described freeze-drying technique [1]. After freeze-drying, these scaffolds were subjected to a dehydrothermal treatment and subsequently chemically crosslinked using EDAC. In vivo performance was assessed using a critical size segmental radial defect (15 mm) introduced into 16 young adult New Zealand White Rabbits under Irish Government license. Animals were divided into three groups; (i) an empty defect group (negative control), (ii) an autogenous bone graft group (positive control) and (iii) a CHA scaffold group (CHA). Segmental defect healing in all animals was assessed using plain X-Ray analysis, at four time-points (0, 6, 12 and 16 weeks). MicroCT and histological analysis were carried out at week 16. Results. Empty defect groups at all time points resulted in non-union of the segmental defect bone ends. Autogenous bone graft groups exhibited good filling of the segmental defect with extensive callus formation but even after 16 weeks showed poor remodelling. Although autogenous bone graft groups showed evidence of mineralized tissue within the defect, tissue healing appeared relatively uncontrolled (Figure 1a). CHA scaffold groups exhibited extensive bone healing as early as 6 weeks. By week 16, CHA defects showed complete bridging across the entire defect (figures 1b, 2b, 3b, 4b), development of a continuous marrow cavity (Figures 2b, 3b, 4b) and evidence of remodelling. Conclusion. The results of this study provide clear evidence that Collagen-HA scaffolds, can perform at least as well as autogenous bone grafts. This study provides strong evidence that after a relatively short time in vivo, CHA scaffolds can result in a more complete and homogenous bone healing response and have the potential to offer improved bone tissue formation above that of autogenous bone. More importantly, this study provides strong evidence that the use of low stiffness, organic, biodegradable scaffolds in fully load-bearing defects is not only successful but arguably produces significantly improved results when compared with the current Gold Standard, autogenous bone grafting

Open femoral fractures are uncommon, and there are very few reports in the literature which refer specifically to their management. The results of the treatment of 31 open femoral fractures with significant bone loss in 29 patients treated in a single Orthopaedic Trauma Unit were reviewed. All fractures underwent wound and bony debridement before skeletal stabilisation at restored femoral length, using primary locked intramedullary nailing or dynamic condylar screw fixation for diaphyseal or metaphyseal fractures respectively. Soft tissue closure was performed at 48 hours in the majority of cases, followed by elective bone grafting procedures for 13 of the fractures. All fractures achieved bony union at an average of 51 weeks (range 20-156 weeks). The time to fracture union and subsequent functional outcome were largely dependent upon the location, type and extent of the bone loss. Union was achieved more rapidly in fractures associated with wedge defects than those with segmental bone loss, and fractures with metaphyseal defects healed more rapidly than those of comparable size in the diaphysis. Metaphyseal wedge fractures did not require any further procedures to achieve union. Complications were more common in the fractures with greater bone loss, which included knee stiffness, delay to union, malunion and leg length discrepancy. One patient had a deep infection, treated by debridement. We have produced an algorithm for the treatment of these injuries, based upon our findings. We feel that satisfactory results can be achieved in most femoral fractures with bone loss, using appropriate initial debridement and modern methods of primary skeletal fixation at a restored femoral length, followed by soft tissue coverage procedures and elective bone grafting, as required

INTRODUCTION. Appropriate, well characterized animal models remain essential for preclinical research. This study investigated a relevant animal model for cancellous bone defect healing. Three different defect diameters of fixed depth were compared in both skeletally immature and mature sheep. This ovine model allows for the placement of four confined cancellous defects per animal. METHODS. Defects were surgically created and placed in the cancellous bone of the medial distal femoral and proximal tibial epiphyses (See Figure 1). All defects were 25 mm deep, with defect diameters of 8, 11, and 14 mm selected for comparison. Defects sites were flushed with saline to remove any residual bone particulate. The skeletally immature and mature animals corresponded to 18 month old and 5 year old sheep respectively. Animals were euthanized at 4 weeks post-operatively to assess early healing. Harvested sites were graded radiographically. The percentage of new bone volume within the total defect volume (BV/TV) was quantified through histomorphometry and μ-CT bone morphometry. Separate regions of interest were constructed within the defect to assess differences in BV/TV between periosteal and deep bone healing. Defect sites were PMMA embedded, sectioned, and stained with basic fuschin and methylene blue for histological evaluation. RESULTS. The animals tolerated the surgery well, with no incidence of fractures within the four weeks. Healing of the defects progressed via endochondral ossification, with none of the defects being completely healed within the 4 week time point. Bone volume fraction (BV/TV) significantly decreased with an increasing defect diameter. Actual bone volume (BV), however, increased with defect diameter, suggesting a correlation between biological response and severity of injury. Three distinct healing regions were found to exist within the defect and along the axis of the defect, with significant differences detected in the BV/TV between adjacent regions. Histologically, the 5 year old animals appeared to have decreased osteoblast activity, and lower osteocyte density within the newly formed woven bone. On occasion, the defects were found to intersect the tibial growth plate in the 18 month old animals, with bone replacing the proliferating chondrocyte zone (See Figure 2). Additionally, the 14 mm defect was not able to be placed in the tibia of sheep due to the possibility of the defect entering the tibial intramedullary (IM) canal, and the lack of cancellous bone between the tibial plateau and IM canal. Both these issues considerably affect this model and should be avoided. CONCLUSION. The surgical placement of 11 mm diameter defects in the proximal tibial and distal femoral epiphyses of skeletally mature sheep presents a suitable large animal model to study early healing of cancellous bone defects. This refined model allows for the placement of four separate non-healing defects within a single sheep, and allows for the possibility to reduce animal numbers required to obtain information

Bone is capable of regeneration, and defects often heal spontaneously. However, cartilage, tendon, and ligament injuries usually result in replacement if the site by organized scar tissue, which is inferior to the native tissue. The osteogenic potential of mesenchymal stem cells (MSCs) has already been verified. MSCs hold great potential for the development of new treatment strategies for a host of orthopedic conditions. The multi-lineage potential and plasticity of MSCs allow them to be building blocks for a host of nonhematopoietic tissues, including bone. More recently, several groups have reported on the successful clinical application of tissue engineering strategies in the repair of bony defects in patients secondary to trauma and tumor resection. Advances in fabrication of biodegradable scaffolds that serve as beds for MSC implantation will hopefully lead to better biocompatibility and host tissue integration. Current strategies for bone tissue engineering include the use of osteoconductive matrix devices that promote bony ingrowth, and the delivery of osteoinductive growth factors, including bone morphogenetic protein (BMP) family, BMP-2 and BMP-7, to bony defect sites. Minimal toxicity has been observed in animal models involving genetically-manipulated stem cells transduced with retroviral and adenoviral vectors. Gene therapy using stem cells as delivery vehicles is a powerful weapon that can be used in a plethora of clinical situations that would benefit from the osteoinductive, proliferative, and angiogenic effects of growth factors. With better understanding of the biology of stem cells in the future and with enhancement of technologies that are capable to influence, modify, and culture these cells, a new field of regenerative skeletal medicine may emerge