Aims. The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes. Methods. Between May 2012 and December 2020, 203 patients with infected segmental bone defects treated with the IMT were enrolled. The digital medical records of these patients were retrospectively analyzed. Factors associated with unfavourable outcomes were identified through logistic regression analysis. Results. Among the 203 enrolled patients, infection recurred in 27 patients (13.3%) after bone grafting. The union rate was 75.9% (154 patients) after second-stage surgery without additional procedures, and final union was achieved in 173 patients (85.2%) after second-stage surgery with or without additional procedures. The mean healing time was 9.3 months (3 to 37). Multivariate logistic regression analysis of 203 patients showed that the number (≥ two) of debridements (first stage) was an independent risk factor for infection recurrence and nonunion. Larger defect sizes were associated with higher odds of nonunion. After excluding 27 patients with infection recurrence, multivariate analysis of the remaining 176 patients suggested that intramedullary nail plus plate internal fixation, smoking, and an allograft-to-autograft ratio exceeding 1:3 adversely affected healing time. Conclusion. The IMT is an effective method to achieve infection eradication and union in the management of infected segmental bone defects. Our study identified several risk factors associated with unfavourable outcomes. Some of these factors are modifiable, and the risk of adverse outcomes can be reduced by adopting targeted interventions or strategies. Surgeons can fully inform patients with non-modifiable risk factors preoperatively, and may even use other methods for bone defect reconstruction. Cite this article: Bone Joint J 2024;106-B(6):613–622

Aims. To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (β-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes. Methods. A review of the medical records was conducted of consecutive 35 lower limbs (30 males and five females; median age 46 years (interquartile range (IQR) 40 to 61)) treated with IMT using β-TCP between 2014 and 2018. Lower Extremity Functional Score (LEFS) was examined preoperatively and at final follow-up to clarify patient-centered outcomes. Bone healing was assessed radiologically, and time from the second stage to bone healing was also evaluated. Patients were divided into ≥ 50 mm and < 50 mm defect groups and into femoral reconstruction, tibial reconstruction, and ankle arthrodesis groups. Results. There were ten and 25 defects in the femur and tibia, respectively. Median LEFS improved significantly from 8 (IQR 1.5 to 19.3) preoperatively to 63.5 (IQR 57 to 73.3) at final follow-up (p < 0.001). Bone healing was achieved in all limbs, and median time from the second stage to bone healing was six months (IQR 5 to 10). Median time to bone healing, preoperative LEFS, or postoperative LEFS did not differ significantly between the defect size groups or among the treatment groups. Conclusion. IMT using β-TCP provided satisfactory clinical and radiological outcomes for segmental bone defects in the lower limbs; surgical outcomes were not influenced by bone defect size or operated part. Cite this article: Bone Joint J 2021;103-B(3):456–461

Aims. The purpose of this study was to: review the efficacy of the induced membrane technique (IMT), also known as the Masquelet technique; and investigate the relationship between patient factors and technique variations on the outcomes of the IMT. Methods. A systematic search was performed in CINAHL, The Cochrane Library, Embase, Ovid MEDLINE, and PubMed. We included articles from 1 January 1980 to 30 September 2019. Studies with a minimum sample size of five cases, where the IMT was performed primarily in adult patients (≥ 18 years old), in a long bone were included. Multivariate regression models were performed on patient-level data to determine variables associated with nonunion, postoperative infection, and the need for additional procedures. Results. A total of 48 studies were included, with 1,386 cases treated with the IMT. Patients had a mean age of 40.7 years (4 to 88), and the mean defect size was 5.9 cm (0.5 to 26). In total, 82.3% of cases achieved union after the index second stage procedure. The mean time to union was 6.6 months (1.4 to 58.7) after the second stage. Our multivariate analysis of 450 individual patients showed that the odds of developing a nonunion were significantly increased in those with preoperative infection. Patients with tibial defects, and those with larger defects, were at significantly higher odds of developing a postoperative infection. Our analysis also demonstrated a trend towards the inclusion of antibiotics in the cement spacer having a protective effect against the need for additional procedures. Conclusion. The IMT is an effective management strategy for complex segmental bone defects. Standardized reporting of individual patient data or larger prospective trials is required to determine the optimal implementation of this technique. This is the most comprehensive review of the IMT, and the first to compile individual patient data and use regression models to determine predictors of outcomes. Cite this article: Bone Joint J 2020;102-B(12):1723–1734

Objectives. The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics. Methods. Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student t-test (two tailed; p < 0.05 was considered significant). Results. Average PMMA spacer in vivo time was 11.9 weeks (six to 18). Trabecular bone was present in 33.3% of the biomembrane specimens; bone presence did not correlate with spacer duration. Biomembrane morphology showed high vascularity and collagen content and positive staining for the key bone forming regulators, bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). Positive differentiation of cultured biomembrane cells for osteogenesis was found in cells from patients with PMMA present for six to 17 weeks. Stem cell differentiation showed greater variability in pluripotency for osteogenic potential (70.0%) compared with chondrogenic or adipogenic potentials (100% and 90.0%, respectively). Significant upregulation of BMP2 and 6, numerous collagens, and bone gla protein was present in biomembrane compared with the cultured cell line. Biomembranes with longer resident PMMA spacer duration (vs those with shorter residence) showed significant upregulation of bone-related, stem cell, and vascular-related genes. Conclusion. The biomembrane technique is gaining favour in the management of complicated bone defects. Novel data on biological mechanisms provide improved understanding of the biomembrane’s osteogenic potential and molecular properties. Cite this article: Dr H. E. Gruber. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Joint Res 2016;5:106–115. DOI: 10.1302/2046-3758.54.2000483

We undertook a retrospective study of 50 consecutive patients (41 male, 9 female) with an infected nonunion and bone defect of the femoral shaft who had been treated by radical debridement and distraction osteogenesis. Their mean age was 29.9 years (9 to 58) and they had a mean of 3.8 (2 to 19) previous operations. They were followed for a mean of 5.9 years (2.0 to 19.0). The mean duration of the distraction osteogenesis was 24.5 months (2 to 39). Pin-track infection was observed in all patients. The range of knee movement was reduced and there was a mean residual leg-length discrepancy of 1.9 cm (0 to 8) after treatment. One patient required hip disarticulation to manage intractable sepsis. In all, 13 patients had persistant pain. Bony union was achieved in 49 patients at a mean of 20.7 months (12 to 35). Although distraction osteogenesis is commonly used for the treatment of infected femoral nonunion with bone defects, it is associated with a high rate of complications

Introduction. Segmental bone defect is a challenging problem. We report our experience of bone transport by hexapod external fixator in patients with segmental defects if the tibia. Method. We report herein 15 patients with segmental bone defect of tibia who completed their treatment protocol. All patients were treated had bone transport with Taylor Spatial Frame from 2012 to 2017. All were treated by the senior author NH. Parameters measured included age, sex, diabetes, smoking, diagnosis, method of fixation prior to treatment use of a free flap, bone defect size, frame-time, external fixation index. Results. Mean age at the time of frame application was 42.7 years. Mean follow-up after frame removal was 23.7 months. Three were diabetic, one smoked and one quit smoking during treatment. Seven had Gustilo-Anderson 3B (47%) and 5 Gustilo-Anderson 3A (33%) open fractures. Three (20%) had closed fractures. Nine (60%) had internal fixation with plate in eight and IM nail in one. Ten patients (67%) had soft tissue defect that required a free flap in seven, local flap in two and skin graft in one. Mean transport was 62 mm. Mean external fixator time and latency were 350.1 and 12 days, respectively. Mean External fixator, distraction and maturation indices were 2.1, 0.52 and 1.43 month per centimeter, respectively. Ten Extra- procedures were required in 7 patients. There were no docking site procedures, non-union of regenerate, adjunctive stabilization after frame removal, recurrence of bone infection and recurrence of deformity. Conclusions. Segmental resection and transport by TSF is an effective method to achieve length, alignment and eradicate infection. Although our cohort had longer external fixator indices than similar studies, the complication rate was low

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks.

In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites.

Aims. This study reviews the use of a titanium mesh cage (TMC) as an adjunct to intramedullary nail or plate reconstruction of an extra-articular segmental long bone defect. Patients and Methods. A total of 17 patients (aged 17 to 61 years) treated for a segmental long bone defect by nail or plate fixation and an adjunctive TMC were included. The bone defects treated were in the tibia (nine), femur (six), radius (one), and humerus (one). The mean length of the segmental bone defect was 8.4 cm (2.2 to 13); the mean length of the titanium mesh cage was 8.3 cm (2.6 to 13). The clinical and radiological records of the patients were analyzed retrospectively. Results. The mean time to follow-up was 55 months (12 to 126). Overall, 16 (94%) of the patients achieved radiological filling of their bony defect and united to the native bone ends proximally and distally, resulting in a functioning limb. Complications included device failure in two patients (12%), infection in two (12%), and wound dehiscence in one (6%). Four patients (24%) required secondary surgery, four (24%) had a residual limb-length discrepancy, and one (6%) had a residual angular limb deformity. Conclusion. A titanium mesh cage is a useful adjunct in the treatment of an extra-articular segmental defect in a long bone. Cite this article: Bone Joint J 2018;100-B:646–51

Aims. In this randomized study, we aimed to compare quality of regenerate in monolateral versus circular frame fixation in 30 patients with infected nonunion of tibia. Patients and Methods. Both groups were comparable in demographic and injury characteristics. A phantom (aluminium step wedge of increasing thickness) was designed to compare the density of regenerate on radiographs. A CT scan was performed at three and six months postoperatively to assess regenerate density. A total of 30 patients (29 male, one female; mean age 32.54 years (18 to 60)) with an infected nonunion of a tibial fracture presenting to our tertiary institute between June 2011 and April 2016 were included in the study. Results. The regenerate mineralization on radiographs was comparable in both groups at two, four, six, and ten months’ follow-up but the rail fixator group had statistically significant higher grades of mineralization when compared with the circular frame group at eight and 12 months’ follow-up. The regenerate mineralization was also higher in the rail fixator group than in the circular frame group on CT at three and six months, although this difference was not statistically significant. Conclusion. Overall, the regenerate mineralization was higher in the monolateral than the circular frame group. A monolateral fixator may be preferred in patients with infected nonunion of the tibia with bone defects up to 7 cm. Cite this article: Bone Joint J 2019;101-B:1416–1422

Aims. Many authors have reported a shorter treatment time when using trifocal bone transport (TFT) rather than bifocal bone transport (BFT) in the management of long segmental tibial bone defects. However, the difference in the incidence of additional procedures, the true complications, and the final results have not been investigated. Patients and Methods. A total of 86 consecutive patients with a long tibial bone defect (≥ 8 cm), who were treated between January 2008 and January 2015, were retrospectively reviewed. A total of 45 were treated by BFT and 41 by TFT. The median age of the 45 patients in the BFT group was 43 years (interquartile range (IQR) 23 to 54). Results. The size of the bone defect was significantly longer (p = 0.005), the number of previous operations was significantly higher (p < 0.001), the operating time was significantly longer (p < 0.001), and the bone transport distance was significantly increased (p = 0.017) in the TFT group. However, the external fixation time (p < 0.001), the healing index (p < 0.001), the number of additional procedures (p = 0.013), and the number of true complications (p < 0.001) were significantly reduced in this group. Both groups achieved highly satisfactory bone and functional results. Conclusion. TFT can significantly reduce the treatment time, the number of additional surgical procedures, and true complications compared with BFT in the treatment of long segmental tibial bone defects

Reconstruction of 10mm segmental bone defects in rat by mesenchymal stem cell derived chondrogenic cells (MSC-DC). Background. Mesenchymal stem cell derived condrogenic cells (MSC-DC) have excellent potential for healing 5 mm bone defect in rat femur. Purpose. To evaluate the effectiveness of MSC-DC on bone healing in 10 mm segmental bone defects in rat femur. Methods. 10 millimeter bone defects were produced in rat femur and fixed with external fixator. We divided this model into four groups according to the kind of graft for bone defects. These bone defects were grafted by MSC-DC seeded on a poly (DL-lactic acid-co-glycolic acid) (PLGA) scaffold in Group A, MSC seeded on a PLGA scaffold in Group B, PLGA scaffold only in Group C, and autologus bone graft in Group D. The healing processes were monitored radiographically and studied biomechanically and histologically. Results. All the bone defects in Group A healed radiographically with bridging callus formation at 4 weeks after the procedure, while none of Group B, C, and D had achieved bone union even at 8 weeks. Mechanical testing revealed that Group A showed approximately 40 % bending strength at 4 weeks compared with the contralateral side, and approximately 60 % at 8 weeks. In histology, Group A, maturation of bridging callus occurred from outside and enchondral ossification was prominent from inside. Conclusion. This study showed that MSC-DC with PLGA scaffold enhances bone healing even in large bone defects

Abstract. Distraction Osteogenesis (DO) for the management of bone defects in long bones is an established technique. Problems with bone regeneration are a common occurrence and literature is full of different modalities to enhance regenerate formation and quality. Strontium Ranelate (SR) has a dual mode of action and enhances bone formation in addition to decreasing osteoclastic activity. Due to this dual mode of action as well as ease of administration in a suspension form, it makes an ideal drug in scenarios where realignment of bone homeostasis towards positive bone balance is desirable. We studied the relationship of administration of SR with rate of regenerate progression, docking site union and complications associated with bone transport in 48 patients undergoing bone transport for management of bone defects. The findings of our retrospective observation study indicated that compliant use of SR was associated with good regenerate progression, decreased problems with docking site union and decreased the need for additional interventions

Combined glenoid and humeral bone loss has been identified as an important factor in predicting recurrence after arthroscopic shoulder stabilisation. The “glenoid track” concept is proposed to predict recurrent instability by comparing the relative size of the glenoid to the humeral bone defect. The aim of this study was to investigate whether assessment of the glenoid track on a pre-operative MR arthrogram could be used to predict subsequent instability in a typical UK population. A retrospective study was undertaken of 175 primary arthroscopic stabilisation procedures of which 82% (n=143) were men. The median age was 26 years (IQR 22 to 32, range 16 to 77). The median follow-up was 76 months (range 21 to 125). A pre-operative MR arthrogram was used to determine if the shoulder was on-track or off-track. The endpoint of recurrent dislocation was examined. The prevalence of “off-track” bone loss in this group was 14.2% (n=25). There were 6 (24%) dislocations in the off-track group compared with 5 (3.33%) dislocations in the on-track group (RR 7.2, 95% CI 2.45 to 20.5, p=0.001). At 5 years, the cumulative redislocation rate was 26.1% in the off-track group compared with 8.7% in on-track group. The rate of any recurrent instability was 60% (n=15) v 18% (n=27) (RR 3.33, 95% CI 2.02 to 5.20, p<0.0001). Glenoid track (on v off) was not predicted by gender (p=0.411). In a typical UK population assessment of the glenoid track on an MR arthrogram can be used to risk stratify patients with shoulder instability

Aims

Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections.

Purpose. The purpose of this study was to evaluate the effects of implantation of mesenchymal stem cell derived condrogenic cells (MSC-DC) on bone healing in segmental defects in rat femur. Methods. Five-millimeter segmental bone defects were produced in the mid-shaft of the femur of Fisher 344 rats and stabilized with external fixator. The Treatment Group received MSC-DC, seeded on a PLGA scaffold, locally at the site of the bone defect, and Control Group received scaffold only. The healing processes were monitored radiographically (Softex), and studied radiographically (Micro-CT) and histologically. Results. All the bone defects in the Treatment Group healed radiographically with bridging callus formation at 4 weeks after the procedure, while none of the Control Group had achieved bone union. Micro-CT showed that newly formed bone volume in the Treatment Group at 16 weeks was 1.5 times that of unaffected side. Histological examination showed that the implanted scaffold of the Treatment Group were covered with periosteum-derived bridging callus and filled with cancellous bone-like tissue derived from enchondral ossification. Conclusion. The results of this study suggest that implantation of MSC-DC surprisingly enhances bone healing in segmental bone defects in rat much better than previously reported similar therapy using MSC

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. The need for a novel, cost effective treatment option for osteochondral defects has therefore never been greater. As an emerging technology, three-dimensional (3D) bioprinting has the capacity to deposit cells, extracellular matrices and other biological materials in user-defined patterns to build complex tissue constructs from the “bottom up”. Through use of extrusion bioprinting and fused deposition modelling (FDM) 3D printing, porous 3D scaffolds were successfully created in this study from hydrogels and synthetic polymers. Mesenchymal stem cells (MSCs) seeded onto polycaprolactone scaffolds with defined pore sizes and porosity maintained viability over a 7-day period, with addition of alginate hydrogel and scaffold surface treatment with NaOH increasing cell adhesion and viability. MSC-laden alginate constructs produced via extrusion bioprinting also maintained structural integrity and cell viability over 7 days in vitro culture. Growth within osteogenic media resulted in successful osteogenic differentiation of MSCs within scaffolds compared to controls (p<0.001). MSC spheroids were also successfully created and bioprinted within a novel, supramolecular hydrogel with tunable stiffness. In conclusion, 3D constructs capable of supporting osteogenic differentiation of MSCs were biofabricated via FDM and extrusion bioprinting. Future work will look to increase osteochondral construct size and complexity, whilst maintaining cell viability

Objectives. Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. Materials and Methods. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. Results. The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). Conclusions. This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials. Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427–435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1

A systematic literature review of distraction osteogenesis (DO) for the primary reconstruction of bone defects following resection of primary malignant tumours of long bones (PMTLB) is presented. Fewer than 50 cases were identified. Most reports relate to benign tumours or secondary reconstructive procedures. The outcomes of our own series of 7 patients is also presented (4 tibiae, 3 femora). All patients had isolated bone lesions without metastases and were assessed through the hospital sarcoma board. Mean follow-up was 59 months (17–144). Mean age was 42 years. Final histologic diagnoses were 3 chondrosarcoma, 2 malignant fibrous histiocytoma, 1 adamantinoma and 1 malignant intraosseous nerve sheath tumour. Mean bone defect after resection was 13.1cm (10–17) and bone transport was the reconstruction method in all. There was one local recurrence of tumour six months post-resection, necessitating amputation. Mean frame index for remaining cases was 30.9 days/cm (15.7–41.6). Complications included pin infection, docking site non-union, premature corticotomy union, soft-tissue infection and minor varus deformity. Six cases remain tumour-free with united, well-aligned bones and good long-term function. We conclude DO provides an effective biologic reconstruction option in select cases of PMTLB

Aims

Open reduction and plate fixation (ORPF) for displaced proximal humerus fractures can achieve reliably good long-term outcomes. However, a minority of patients have persistent pain and stiffness after surgery and may benefit from open arthrolysis, subacromial decompression, and removal of metalwork (ADROM). The long-term results of ADROM remain unknown; we aimed to assess outcomes of patients undergoing this procedure for stiffness following ORPF, and assess predictors of poor outcome.

Common cell based strategies for treating bone defects require time-consuming and expensive isolation and expansion of autologous cells. We developed a novel expedited technology creating gene activated muscle grafts. We hypothesized that BMP-2 activated muscle grafts provide healing capabilities comparable to autologous bone grafting, the clinical gold standard. Two male, syngeneic Fischer 344 rats served as tissue donors. Muscle tissue was harvested from hind limbs and incubated with an adenoviral vector carrying the cDNA encoding BMP-2. Bone tissue was harvested from the iliac crest. Segmental bone defects were created in the right femora of 12 rats and were filled with either BMP-2 activated muscle tissue or bone grafts. After 8 weeks, femora were evaluated by radiographs, microCT, and biomechanical tests. BMP-2 activated muscle grafts and autologous bone grafts resulted in complete mineralization and healing, as documented by radiographs and microCT. Bone volume in the muscle graft defects (33+/-12mm3) was similar to autologous bone graft defects (39+/-5mm3). Torque at failure of the two groups was statistically indistinguishable (240+/-115 Nmm vs. 232+/-108Nmm). In previous experiments we demonstrated that the large segmental defect model in this study will not heal with either empty defects or non-activated muscle grafts. Our findings therefore demonstrate that BMP-2 gene activation of muscle tissue effectively stimulates defect healing similar to autologous bone grafts