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

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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.

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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.

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Our objective was to conduct a systematic review and meta-analysis, to establish whether differences arise in clinical outcomes between autologous and synthetic bone grafts in the operative management of tibial plateau fractures.

Introduction. The treatment of large segmental defects of long bones, which is caused by high energy trauma, revision surgery and resection of tumor or osteomyelitis and so on, is usually difficult. Recently the usefulness of Induced membrane technique (Masquelet technique) is reported. Induced membrane technique is an alternative method to reconstruct long-bone defects, which is two-stage surgery and combines the use of induced pseudo-membranes and cancellous autografts. The mechanism of bone formation in this technique is unknown. We performed Induced membrane technique on four patients, collected their membranes, and tested osteogenic ability and multipotency of cells derived from the membrane. Material and Method. From 2011, we had 4 patients of large segmental defects of long bones, which underwent operations of induced membrane technique. All operation performed by one surgeon. There were 2 nonunion (2 femur) and 1 open fracture (tibia), and close comminuted fracture (femur). Average length of bone defects was 5 cm. On the second stage, we collect some membranes and cultured cells derived from them. Then, cultured cells were tested for the ability to differentiate in vitro to multiple lineage. Results. Average period of bony union was 16 weeks. Cells (Passage 0) formed calcium deposition. Cells (Passage 3) differentiated into Adipogenic, chondrogenic, and osteogenic lineage in 3 weeks. Conclusion. Induced membrane derived cells have ability of bone synthesis and multipotency

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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.

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

Introduction. The concept of “bone graft expanders” has been popularised to increase the volume and biological activity of the implanted Material. HYPOTHESIS. Orthoss® granules support exogenously seeded MSCs and attract neighbouring host MSCs. Methods. In 3-D cultures’ Orthoss® granules were seeded with 2×10. 5. bone marrow MSCs/granule and maintained in MSC expansion or differentiation media for 21 days. In homing experiments’ bone autografts were placed in close proximity to Orthoss®. Scaffold colonisation and MSC differentiation were assessed by confocal microscopy’ standard electron microscopy’ and energy-dispersive X-ray spectroscopy. Results. Long-term incubation of MSC/scaffold resulted in formation of multiple cell-matrix layers lining the scaffold pores as well as outer surfaces. MSC differentiation to osteoblasts was evident as strong deposition of Calcium and Phosphorus was detected in both MSC expansion and osteogenic conditions. Cell egress experiments demonstrated the migration of cells from neighbouring autografts and their attachment and re-settlement on Orthoss®. Discussion & Conclusions. Orthoss® scaffolds support MSC attachment’ growth and osteogenic differentiation whereas resident bone subpopulations can rapidly migrate towards’ attach’ and expand on them. These results indicate that Orthoss® can serve as a graft expander for repairing large bone defects in trauma patients

We hypothesise that the Masquelet induced membrane used for the reconstruction of large bone defects were likely to involve mesenchymal stem cells (MSCs), given the excellent resultant skeletal repair. This study represents the first characterisation in humans of the induced membrane formed as a result of the Masquelet technique. Methods. Induced membranes and matching periosteum were harvested from 7 patients. Cytokines (BMP2, VEGF, SDF1) and cell lineage markers (CD31, CD271, CD146) were studied by immunohistochemisty. Flow cytometry was used to measure the cellularity and cellular composition. MSCs were enumerated using a colony forming unit fibroblast assay. In expanded cultures, a 96-gene array card was used to assess their transcriptional profile. Alkaline phophatase, alizarin red and calcium assays were employed to measure their in vitro osteogenic potential. Results. Membrane was more cellular(p=0.028), had more MSC phenotype(p=0.043) compared to matched periosteum. The molecular profiles were similar, except for 2-fold abundance of SDF-1 in membrane (p=0.043)compared to periosteum. Membrane and periosteum had a similar proportion of endothelial cells and CFU-F colonies; expanded MSCs from both sources were highly osteogenic. Discussion. These results indicate that the induced membrane possesses a rich source of MSC and therefore our findings support the view that the induced membrane plays an active role in bone regeneration

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

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

The reconstruction of lower limb defects after oncological reconstructions is still a problem in limb salvage surgery. Large bony defects need to be treated with sound and durable reconstructions. During recent decades, the life expectancy of patients affected with cancer has improved considerably because of advances in chemotherapy, immunotherapy, hormonal treatment and radiotherapy. This improvement requires greater reliability in the reconstructive procedure in order to avoid mechanical failure during prolonged survival of the patient. The author experience with modular megaprosthesis by Link (megasystem C) allowed us to present a rapid, effective and functional solution. From June 2001 to December 2007 225 patients have been operated with a megaprosthesis C for tumoral resection. The new megaprosthesis C by Link represents a wide-ranging system that can afford a large variety of reconstructions in the inferior limb, from very short replacement of 5 cm in proximal femur, to a total femur and proximal tibia replacement. Modularity is represented by 1 cm increase in length. The different options of cemented and not cemented stem may be used with intraoperative decision. In cemented stem a rough collar seals the osteotomy and prevents polyethylene debris from entering the femoral canal by inducing a scar tissue around the stem entrance (so-called purse-string effect). Moreover in patients with solitary lesions and very good prognosis an allograft-prosthesis composite can be performed with improved clinical results on walking and function. Of the 225 patients that underwent tumoral resection and reconstruction with a modular megaprosthesis approximately 43% (97 cases) were operated for metastatic disease. Among these cases 55 cases were proximal femoral recontructions, 39 cases were distal femoral reconstructions and 3 cases were proximal tibial reconstructions. All cases were performed with cemented stems. We experienced a 7% of postoperative infections, 2% of dislocations of proximal femoral prosthesis and 3% of mechanical failures. While infections and dislocation rates were in the average for this surgery, mechanical failures were relatively high. We should consider that in patients with relatively long resections and muscle deficiency the mechanical stress exerted on the prosthesis can explain this kind of mechanical failure. However the new design of morse tapers have annulled these problems

We studied the outcome and functional status of 33 patients with 34 severe open tibial fractures (Gustilo grade IIIb and IIIc). The treatment regime consisted of radical debridement, immediate bony stabilisation and early soft-tissue cover using a muscle flap (free or rotational). The review included standardised assessments of health-related quality of life (SF-36 and Euroqol) and measurement of the following parameters: gait, the use of walking aids, limb-length discrepancy, knee and ankle joint function, muscle wasting and the cosmetic appearance of the limb. Personal comments and overall patient satisfaction were also recorded. The mean follow-up was 46 months (15 to 80). There were 30 Gustilo grade IIIb fractures and and four grade IIIc fractures. Of the 33 patients, 29 had primary internal fixation and four, external fixation; 11 (34%) later required further surgery to achieve union and two needed bone transport procedures to reconstruct large segmental defects. The mean time to union was 41 weeks (12 to 104). Two patients (6.1%) developed deep infection; both resolved with treatment. The mean SF-36 physical and mental scores were 49 and 62 respectively. The mean state of health score for the Euroqol was 68. Patients with isolated tibial fractures had a better outcome than those with other associated injuries on both scoring systems. Knee stiffness was noted in seven patients (21%) and ankle stiffness in 19 (56%); 12 patients (41%) returned to work. Our results compare favourably with previous outcome measurements published for both limb salvage and amputation. All patients were pleased to have retained their limbs

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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.

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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.

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This study describes the use of the Masquelet technique to treat segmental tibial bone loss in 12 patients.

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To evaluate the outcomes of cemented total hip arthroplasty (THA) following a fracture of the acetabulum, with evaluation of risk factors and comparison with a patient group with no history of fracture.

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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.

The results of the treatment of 31 open femoral fractures (29 patients) with significant bone loss in a single trauma unit were reviewed. A protocol of early soft-tissue and bony debridement was followed by skeletal stabilisation using a locked intramedullary nail or a dynamic condylar plate for diaphyseal and metaphyseal fractures respectively. Soft-tissue closure was obtained within 48 hours then followed, if required, by elective bone grafting with or without exchange nailing.

The mean time to union was 51 weeks (20 to 156). The time to union and functional outcome were largely dependent upon the location and extent of the bone loss. It was achieved more rapidly in fractures with wedge defects than in those with segmental bone loss. Fractures with metaphyseal defects healed more rapidly than those of comparable size in the diaphysis. Complications were more common in fractures with greater bone loss, and included stiffness of the knee, malunion and limb-length discrepancy.

Based on our findings, we have produced an algorithm for the treatment of these injuries. We conclude that satisfactory results can be achieved in most femoral fractures with bone loss using initial debridement and skeletal stabilisation to maintain length, with further procedures as required.

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.