Aims. Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects. Methods. We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures. Results. Mean follow-up was 39.5 months (36 to 71), with a significant improvement in post-revision function compared to preoperative function. Graft site remodelling was rated radiologically as moderate in 31 hips (63%) and strong in 12 hips (24%). There were no cases of complete graft site dissolution. No acetabular loosening was identified. None of the patients developed clinically significant heterotopic ossification. There were twelve reoperations: six patients developed post-revision infections, three experienced dislocations, two sustained periprosthetic femur fractures, and one subject had femoral component aseptic loosening. Conclusion. Our series reports bone defect restoration with the sole use of a biphasic injectable BGS in the periacetabular region. We did not observe significant graft dissolution. We emphasize that successful graft site remodelling requires meticulous recipient site preparation. Cite this article: Bone Jt Open 2022;3(12):991–997

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

Resection of a primary sarcoma of the diaphysis of a long bone creates a large defect. The biological options for reconstruction include the use of a vascularised and non-vascularised fibular autograft. The purpose of the present study was to compare these methods of reconstruction. Between 1985 and 2007, 53 patients (26 male and 27 female) underwent biological reconstruction of a diaphyseal defect after resection of a primary sarcoma. Their mean age was 20.7 years (3.6 to 62.4). Of these, 26 (49 %) had a vascularised and 27 (51 %) a non-vascularised fibular autograft. Either method could have been used for any patient in the study. The mean follow-up was 52 months (12 to 259). Oncological, surgical and functional outcome were evaluated. Kaplan–Meier analysis was performed for graft survival with major complication as the end point. At final follow-up, eight patients had died of disease. Primary union was achieved in 40 patients (75%); 22 (42%) with a vascularised fibular autograft and 18 (34%) a non-vascularised (p = 0.167). A total of 32 patients (60%) required revision surgery. Kaplan–Meier analysis revealed a mean survival without complication of 36 months (0.06 to 107.3, . sd. 9) for the vascularised group and 88 months (0.33 to 163.9, . sd. 16) for the non-vascularised group (p = 0.035). . Both groups seem to be reliable biological methods of reconstructing a diaphyseal bone defect. Vascularised autografts require more revisions mainly due to problems with wound healing in distal sites of tumour, such as the foot. Cite this article: Bone Joint J 2014;96-B:1258–63

Aims. This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes. Methods. A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data. Results. After the screening, 44 studies were included with 1,079 patients and 1,083 segments of infected bone defects treated with the induced membrane technique. The mean defect size was 6.8 cm (0.5 to 30). After the index second stage procedure, 85% (797/942) of segments achieved union, and 92% (999/1,083) of segments achieved final healing. The multivariate analysis with data from 296 patients suggested that older age was associated with higher nonunion risk. Patients with external fixation in the second stage had a significantly higher risk of developing nonunion, increasing the need for additional procedures. The autografts harvested from the femur reamer-irrigator-aspirator increased nonunion, infection recurrence, and additional procedure rates. Conclusion. The induced membrane technique is an effective technique for treating infected bone defects. Internal fixation during the second stage might effectively promote bone healing and reduce additional procedures without increasing infection recurrence. Future studies should standardize individual patient data prospectively to facilitate research on the affected patient outcomes. Cite this article: Bone Joint Res 2023;12(9):546–558

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. This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis. Methods. We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed. Results. In total, 314 patients with a mean age of 52.1 years (SD 12.1) were enrolled. After a mean of 50 months’ (24 to 96) follow-up, 53 (16.9%) patients had infection recurrence including 32 tibiae, ten femora, ten calcanea, and one humerus. Of all patients with recurrence, 30 (9.6%) occurred within one year and 39 (12.4%) within two years. Among them, 41 patients needed reoperation, five received antibiotics treatment only, and seven ultimately required amputations. Following multivariable analysis, we found that patients infected with Gram-negative bacilli were more likely to have a recurrence (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.20 to 6.94; p = 0.046) compared to Staphylococcus aureus; segmental bone defects (OR 5.25, 95% CI 1.80 to 15.26; p = 0.002) and smoking (OR 3.00, 95% CI 1.39 to 6.50; p = 0.005) were also independent risk factors for recurrence after treatment. Conclusion. Permanent ALCS might be an alternative strategy for definitive bone defect management in selected osteomyelitis cases. However, the overall high recurrence found suggests that it should be cautiously treated. Additionally, segmental defects, Gram-negative infections, and smoking were associated with an increased risk of infection recurrence. Cite this article: Bone Joint Res 2023;12(8):467–475

Aims. Large bone defects resulting from osteolysis, fractures, osteomyelitis, or metastases pose significant challenges in acetabular reconstruction for total hip arthroplasty. This study aimed to evaluate the survival and radiological outcomes of an acetabular reconstruction technique in patients at high risk of reconstruction failure (i.e. periprosthetic joint infection (PJI), poor bone stock, immunosuppressed patients), referred to as Hip Reconstruction In Situ with Screws and Cement (HiRISC). This involves a polyethylene liner embedded in cement-filled bone defects reinforced with screws and/or plates for enhanced fixation. Methods. A retrospective chart review of 59 consecutive acetabular reconstructions was performed by four surgeons in a single institution from 18 October 2018 to 5 January 2023. Cases were classified based on the Paprosky classification, excluding type 1 cases (n = 26) and including types 2 or 3 for analysis (n = 33). Radiological loosening was evaluated by an orthopaedic surgeon who was not the operating surgeon, by comparing the immediate postoperative radiographs with the ones at latest follow-up. Mean follow-up was 557 days (SD 441; 31 to 1,707). Results. Out of the 33 cases analyzed, six (18.2%) constructs required revision, with four revisions due to uncontrolled infection, one for dislocation, and one for aseptic loosening. Among the 27 non-revised constructs, only one showed wider radiolucencies compared to immediate postoperative radiographs, indicating potential loosening. Patients who underwent revision (n = 6) were significantly younger and had a higher BMI compared to those with non-revised constructs (p = 0.016 and p = 0.026, respectively). Sex, race, ethnicity, American Society of Anesthesiologists grade, infection status (patients with postoperative PJI diagnosis (septic) vs patients without such diagnosis (aseptic)), and mean follow-up did not significantly differ between revised and non-revised groups. Conclusion. The HiRISC technique may serve as a feasible short-term (about one to two years) alternative in patients with large acetabular defects, particularly in cases of PJI. Longer follow-up is necessary to establish the long-term survival of this technique. Cite this article: Bone Joint J 2024;106-B(5 Supple B):82–88

The Cierny and Mader classification assists with decision-making in the management of osteomyelitis by strafying the host status and the pathoanatomy of disease. However the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08– 8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistical significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time

Introduction. The Cierny and Mader classification assists with decision-making by stratifying host status and the pathoanatomy of the disease. However, the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. Materials & Methods. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Results. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08–8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistically significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). Conclusions. This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time

Aim. The primary endpoint of this study is to characterize the progression of bone defects at the femoral and tibial side in patients who sustained PJI of the knee that underwent two-stage revision with spacer implantation. In addition, we want to analyze the differences between functional moulded and hand-made spacers. Methods. A retrospective analysis of patients that underwent two-stage revision due to PJI of the knee between January 2014 and December 2021 at our institution. Diagnosis of infection was based on the criteria of the Muscoloskeletal Infection Society. The bone defect evaluation was performed intraoperatively based on the AORI classification. The basal evaluation was performed at the time the resection arthroplasty and spacer implantation surgery. The final evaluation was performed at the second-stage surgery, at the time of spacer removal and revision implant positioning. The differences between groups were characterized by using T-test student for continuous variables, and by using chi-square for categorical variables. A p-value < 0.05 was defined as significant. Results. Complete data of 37 two-stage TKAs revision were included in the study. An articulating moulded functional spacer was used in 14 (35.9%) cases, while a hand-made spacer was used in 23 (58.9%) cases. The average length of interval period (excluding the time for patients that retained the spacer) was 146.6 days. A bone defects progression based on the AORI classification was documented in 24 cases at the femoral side (61.6%), a bone defect progression was documented in 17 cases at the tibial side (43.6%), and a bone defect at both sides was documented in 13 cases (33.3%). A statistically significant greater bone defect progression at the tibial side was observed when hand-made spacers were used. A complication during the interval period was reported in five cases (12.8%) and postoperative complication was reported in 9 cases (23.1%). Conclusions. When comparing patients in which a functional articulating spacer was used, with patients in which static spacer was used, we reported a statistically significant reduced bone defect progression during the interval period at the femoral side only when moulded spacers were used. We observed a higher incidence of bone defect progression also at the tibial and both sides when hand-made spacers were used. This is the first study that documented the bone defect progression during two-stage revision of the knee, the results observed in this study are very encouraging

Introduction. A significant burden of disease exists with respect to critical sized bone defects; outcomes are unpredictable and often poor. There is no absolute agreement on what constitutes a “critically-sized” bone defect however it is widely considered as one that would not heal spontaneously despite surgical stabilisation, thus requiring re-operation. The aetiology of such defects is varied. High-energy trauma with soft tissue loss and periosteal stripping, bone infection and tumour resection all require extensive debridement and the critical-sized defects generated require careful consideration and strategic management. Current management practice of these defects lacks consensus. Existing literature tells us that tibial defects 25mm or great have a poor natural history; however, there is no universally agreed management strategy and there remains a significant evidence gap. Drawing its origins from musculoskeletal oncology, the Capanna technique describes a hybrid mode of reconstruction. Mass allograft is combined with a vascularised fibula autograft, allowing the patient to benefit from the favourable characteristics of two popular reconstruction techniques. Allograft confers initial mechanical stability with autograft contributing osteogenic, inductive and conductive capacity to encourage union. Secondarily its inherent vascularity affords the construct the ability to withstand deleterious effects of stressors such as infection that may threaten union. The strengths of this hybrid construct we believe can be used within the context of critical-sized bone defects within tibial trauma to the same success as seen within tumour reconstruction. Methodology. Utilising the Capanna technique in trauma requires modification to the original procedure. In tumour surgery pre-operative cross-sectional imaging is a pre-requisite. This allows surgeons to assess margins, plan resections and order allograft to match the defect. In trauma this is not possible. We therefore propose a two-stage approach to address critical-sized tibial defects in open fractures. After initial debridement, external fixation and soft tissue management via a combined orthoplastics approach, CT imaging is performed to assess the defect geometry, with a polymethylmethacrylate (PMMA) spacer placed at index procedure to maintain soft tissue tension, alignment and deliver local antibiotics. Once comfortable that no further debridement is required and the risk of infection is appropriate then 3D printing technology can be used to mill custom jigs. Appropriate tibial allograft is ordered based on CT measurements. A pedicled fibula graft is raised through a lateral approach. The peroneal vessels are mobilised to the tibioperoneal trunk and passed medially into the bone void. The cadaveric bone is prepared using the custom jig on the back table and posterolateral troughs made to allow insertion of the fibula, permitting some hypertrophic expansion. A separate medial incision allows attachment of the custom jig to host tibia allowing for reciprocal cuts to match the allograft. The fibula is implanted into the allograft, ensuring nil tension on the pedicle and, after docking the graft, the hybrid construct is secured with multi-planar locking plates to provide rotational stability. The medial window allows plate placement safely away from the vascular pedicle. Results. We present a 50-year-old healthy male with a Gustilo & Anderson 3B proximal tibial fracture, open posteromedially with associated shear fragment, treated using the Capanna technique. Presenting following a fall climbing additional injuries included a closed ipsilateral calcaneal and medial malleolar fracture, both treated operatively. Our patient underwent reconstruction of his tibia with the above staged technique. Two debridements were carried out due to a 48-hour delay in presentation due to remote geographical location of recovery. Debridements were carried out in accordance with BOAST guidelines; a spanning knee external fixator applied and a small area of skin loss on the proximal medial calf reconstructed with a split thickness skin graft. A revision cement spacer was inserted into the metaphyseal defect measuring 84mm. At definitive surgery the external fixator was removed and graft fixation was extended to include the intra-articular fragments. No intra-operative complications were encountered during surgeries. The patient returned to theatre on day 13 with a medial sided haematoma. 20ml of haemoserous fluid was evacuated, a DAIR procedure performed and antibiotic-loaded bioceramics applied locally. Samples grew Staphylococcus aureus and antibiotic treatment was rationalised to Co-Trimoxazole 960mg BD and Rifampicin 450mg BD. The patient has completed a six-week course of Rifampicin and continues on suppressive Co-Trimoxazole monotherapy until planned metalwork removal. There is no evidence of ongoing active infection and radiological evidence of early union. The patient is independently walking four miles to the gym daily and we believe, thus far, despite accepted complications, we have demonstrated a relative early success. Conclusions. A variety of techniques exist for the management of critical-sized bone defects within the tibia. All of these come with a variety of drawbacks and limitations. Whilst acceptance of a limb length discrepancy is one option, intercalary defects of greater than 5 to 7cm typically require reconstruction. In patients in whom fine wire fixators and distraction osteogenesis are deemed inappropriate, or are unwilling to tolerate the frequent re-operations and potential donor site morbidity of the Masqualet technique, the Capanna technique offers a novel solution. Through using tibial allograft to address the size mismatch between vascularised fibula and tibia, the possible complication of fatigue fracture of an isolated fibula autograft is potentially avoidable in patients who have high functional demands. The Capanna technique has demonstrated satisfactory results within tumour reconstruction. Papers report that by combining the structural strength of allograft with the osteoconductive and osteoinductive properties of a vascularised autograft that limb salvage rates of greater than 80% and union rates of greater than 90% are achievable. If these results can indeed be replicated in the management of critical-sized bone defects in tibial trauma we potentially have a treatment strategy that can excel over the more widely practiced current techniques

The Masquelet technique is a variable method for treating critical-sized bone defects, but there is a need to develop a technique for promoting bone regeneration. In recent studies of bone fracture healing promotion, macrophage-mesenchymal stem cell (MSC) cross-talk has drawn attention. This study aimed to investigate macrophage expression in the induced membrane (IM) of the Masquelet technique using a mouse critical-sized bone defect model. The study involved a 3-mm bone defect created in the femur of mice and fixed with a mouse locking plate. The Masquelet (M) group, in which a spacer was inserted, and the Control (C) group, in which the defect was left intact, were established. Additionally, a spacer was inserted under the fascia of the back (B group) to form a membrane due to the foreign body reaction. Tissues were collected at 1, 2, and 4 weeks after surgery (n=5 in each group), and immunostaining (CD68, CD163: M1, M2 macrophage markers) and RT-qPCR were performed to investigate macrophage localization and expression in the tissues. The study found that CD68-positive cells were present in the IM of the M group at all weeks, and RT-qPCR showed the highest CD68 expression at 1 week. In addition, there was similar localization and expression of CD163. The C group showed lower expression of CD68 and CD163 than the M group at all weeks. The B group exhibited CD68-positive cells in the fibrous capsule and CD163-positive cells in the connective tissue outside the capsule, with lower expression of both markers compared to the M group at all weeks. Macrophage expression in IM in M group had different characteristics compared to C group and B group. These results suggest that the IM differs from the fibrous capsules due to the foreign body reaction, and the macrophage-MSC cross-talk may be involved in Masquelet technique

Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation. Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263–273. DOI: 10.1302/2046-3758.74.BJR-2018-0006

Introduction. Acetabular bone defects are still challenging to quantify. Numerous classification schemes have been proposed to categorize the diverse kinds of defects. However, these classification schemes are mainly descriptive and hence it remains difficult to apply them in pre-clinical testing, implant development and pre-operative planning. By reconstructing the native situation of a defect pelvis using a Statistical Shape Model (SSM), a more quantitative analysis of the bone defects could be performed. The aim of this study is to develop such a SSM and to validate its accuracy using relevant clinical scenarios and parameters. Methods. An SSM was built on the basis of segmented 66 CT dataset of the pelvis showing no orthopedic pathology. By adjusting the SSM's so called modes of shape variation it is possible to synthetize new 3D pelvis shapes. By fitting the SSM to intact normal parts of an anatomical structure, missing or pathological regions can be extrapolated plausibly. The validity of the SSM was tested by a Leave-one-out study, whereby one pelvis at a time was removed from the 66 pelvises and was reconstructed using a SSM of the remaining 65 pelvises. The reconstruction accuracy was assessed by comparing each original pelvis with its reconstruction based on the root-mean-square (RMS) surface error and five clinical parameters (center of rotation, acetabulum diameter, inclination, anteversion, and volume). The influence of six different numbers of shape variation modes (reflecting the degrees of freedom of the SSM) and four different mask sizes (reflecting different clinical scenarios) was analyzed. Results. The Leave-one-out study showed that the reconstruction errors decreased when the number of shape variation modes included in the SSM increased from 0 to 20, but remained almost constant for higher numbers of shape variation modes. For the SSM with 20 shape variation modes, the RMS of the reconstruction error increased with increasing mask size, whereas the other parameters only increased from Mask_0 to Mask_1, but remained almost constant for Mask_1, Mask_2 and Mask_3. Median reconstruction errors for Mask_1, Mask_2, and Mask_3 were approximately 3 mm in Center of Rotation (CoR) position, 2 mm in Diameter, 3° in inclination and anteversion, as well as 5 ml in volume. Discussion. This is the first study analyzing and showing the feasibility of a quantitative analysis of acetabular bone defects using a SSM-based reconstruction method in the clinical scenario of a defect or implant in both acetabuli and incomplete CT-scans. Validation results showed acceptable reconstruction accuracy, also for clinical scenarios in which less healthy bone remains. Further studies could apply this method on a larger number of defect pelvises to obtain quantitative measures of acetabular bone defects

Segmental bone transport (SBT) with an external fixator has become a standard method for treatment of large bone defect. However, a long time-application of devices can be very troublesome and complications such as nonunion is sometimes seen at docking site. Although there have been several studies on SBT with large animal models, they were unsuitable for conducting drug application to improve SBT. The purpose of this study was to establish a bone transport model in mice. Six-month-old C57BL/6J mice were divided randomly into bone transport group (group BT) and an immobile control group (group EF). In each group, a 2-mm bone defect was created in the right femur. Group BT was reconstructed by SBT with external fixator (MouseExFix segment transport, RISystem, Switzerland) and group EF was fixed simply with unilateral external fixator (MouseExFix simple). In group BT, a bone segment was transported by 0.2 mm per day. Radiological and histological studies were conducted at 3 and 8 weeks after the surgery. In group BT, radiological data showed regenerative new bone consolidation at 8 weeks after the surgery, whereas high rate of nonunion was observed at the docking site. Histological data showed intramembranous and endochondral ossification. Group EF showed no bone union. In this study, experimental group showed good regenerative new bone formation and was similar ossification pattern to previous large animal models. Thus, the utilization of this bone defect mice model allows to design future studies with standardized mechanical conditions for analyzing mechanisms of bone regeneration induced by SBT

Objectives. Long bone defects often require surgical intervention for functional restoration. The ‘gold standard’ treatment is autologous bone graft (ABG), usually from the patient’s iliac crest. However, autograft is plagued by complications including limited supply, donor site morbidity, and the need for an additional surgery. Thus, alternative therapies are being actively investigated. Autologous bone marrow (BM) is considered as a candidate due to the presence of both endogenous reparative cells and growth factors. We aimed to compare the therapeutic potentials of autologous bone marrow aspirate (BMA) and ABG, which has not previously been done. Methods. We compared the efficacy of coagulated autologous BMA and ABG for the repair of ulnar defects in New Zealand White rabbits. Segmental defects (14 mm) were filled with autologous clotted BM or morcellized autograft, and healing was assessed four and 12 weeks postoperatively. Harvested ulnas were subjected to radiological, micro-CT, histological, and mechanical analyses. Results. Comparable results were obtained with autologous BMA clot and ABG, except for the quantification of new bone by micro-CT. Significantly more bone was found in the ABG-treated ulnar defects than in those treated with autologous BMA clot. This is possibly due to the remnants of necrotic autograft fragments that persisted within the healing defects at week 12 post-surgery. Conclusion. As similar treatment outcomes were achieved by the two strategies, the preferred treatment would be one that is associated with a lower risk of complications. Hence, these results demonstrate that coagulated BMA can be considered as an alternative autogenous therapy for long bone healing. Cite this article: Z. X. H. Lim, B. Rai, T. C. Tan, A. K. Ramruttun, J. H. Hui, V. Nurcombe, S. H. Teoh, S. M. Cool. Autologous bone marrow clot as an alternative to autograft for bone defect healing. Bone Joint Res 2019;8:107–117. DOI: 10.1302/2046-3758.83.BJR-2018-0096.R1

Objectives. Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients. Methods. A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft. Results. The patients were followed for 27.5 months (24 to 32). Radiographic bone union occurred at six months for 26 cases (81%) and clinical healing occurred in 29 cases (90%) at ten months. A total of six cases had a second debridement before bone grafting because of recurrence of infection and one patient required a third debridement. No cases of osteomyelitis had recurred at the time of the last follow-up visit. Conclusion. The induced membrane technique for the treatment of post-traumatic osteomyelitis is a simple, reliable method, with good early results. However, there are many challenges in determining the scope of the debridement, type of limb fixation and source of bone graft to be used. Cite this article: Dr Z. Xie. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis. Bone Joint Res 2016;5:101–105. DOI: 10.1302/2046-3758.53.2000487

Adrenomedullin is a peptide hormone that has attracted attention with its proliferative and anti-apoptotic effects on osteoblasts in recent years. We investigated the effect of adrenomedullin on healing of the segmental bone defect in a rat model. 36 Wistar rats were randomly divided in six groups based on follow-up periods and administered dose of adrenomedullin hormone. In each group, a 2 mm bone defect was created at the diaphysis of radius, bilaterally. NaCl solution was administered to sham groups three times a week for 4 and 8 weeks, intraperitoneally. Adrenomedullin was administered to study groups three times a week; 15 µg-4 weeks, 15 µg-8 weeks, 30 µg-4 weeks and 30 µg-8 weeks, respectively. After euthanasia, the segmental defects were evaluated by histomorphometric (new bone area (NBA)) and micro-tomographic (bone volume (BV), bone surface (BS), bone mineral density (BMD)) analysis. Although 4 and 8 weeks 15 μg administered study groups had higher NBA values than the other study and control groups, histomorphometric analysis did not reveal any statistical difference between the control and study groups in terms of new bone area (p > 0.05). In micro-tomographic analysis, BV was higher in 15 μg – 4 weeks group than 30 μg – 4 weeks group (296.9 vs 208.5, p = 0.003) and BS was lower in 30 μg – 4 weeks than 4 week - control group (695.5 vs 1334.7, p = 0.005) but in overall, no significant difference was found between the control and study groups (p > 0.05). Despite these minor differences in histomorphometric and micro-tomographic criteria indicating new bone formation, BMD values of 15 µg-4 and −8 weeks study groups showed significant increase comparing with the control group (p = 0.04, p = 0.001, respectively). Adrenomedullin seemed to have a positive effect on BMD at a certain dose (15 µg) but it alone is not considered sufficient for healing of the defect with new bone formation. Further studies are needed to assess its effects on bone tissue trauma. This study was funded by Hacettepe University Scientific Research Projects Coordination Unit

Purpose. The aim of this study was to compare the clinical outcomes of the revision TKA in which trabecular metal cones and femoral head allografts were used for large bone defect. Method. Total 53 patients who have undergone revision TKA from July 2013 to March 2017 were enrolled in this study. Among them, 24 patients used trabecular metal cones, and 29 patients used femoral head allografts for large bone defect. There were 3 males and 21 females in the metal cone group, while there were 4 males and 25 females in the allograft group. The mean age was 70.2 years (range, 51–80) in the femoral head allograft group, while it was 79.1 years (range, 73–85) in the metal cone group. Bone defect is classified according to the AORI classification and clinical outcomes were evaluated with Visual Analogue Scale (VAS), Hospital Special Surgery-score (HSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), and ROM. Operation time was also evaluated. We used radiographs to check complications such as migration or loosening. We took follow-up x-rays and 3D CT of the patients, to assess the mean bone union period. Shapiro-Wilk test was done to check normality and Student T-test and Mann Whitney U-test were done for comparison between two groups. Result. The mean follow-up period was 3 .75 years (Range; 2.1 ∼ 5.75). The pre-op scores did not show significant difference. The mean VAS in the allograft and trabecular metal cone groups was 2.1 ± 0.87 and 1.8 ± 0.53, respectively (p = 0.16). The mean HSS score were 76.3 ± 5.51 and 79.2 ± 4.12 respectively (p = 0.13) and the mean WOMAC scores were 15.1 ± 3.25 and 14.8 ± 3.31 respectively (p = 0.06), and the mean KOOS scores were 27.8 ± 4.77 and 25.5 ± 4.84, respectively (p = 0.07). The mean ROM ranges were 100.6 ± 17.54 and 101.3 ± 19.22, respectively (p = 0.09). But the mean operation time of the allograft and trabecular metal cone groups was 137 minutes (Range; 111–198) and 102minutes (Range; 93 −133) (p=0.02) respectively, which showed statistical significance. In follow-up x-rays, no migration or loosening of the implants, osteolysis and other complications were found in both groups. In follow-up 3D CT, osteointegration was seen at the trabecular metal cone site, host bone being interpreted to the host bone. The allograft group showed fibrous and stable union in follow-up 3D CT. Conclusion. According to this study, in case of revision TKA with large bone defect, using whether allograft or trabecular metal cones did not affect the clinical outcomes. However, operation time was significantly shorter in trabecular metal cone group, therefore, in patients with poor general condition along with severe underlying diseases, usage of trabecular metal cone would be a better choice to shorten operation time and ease postoperative care. Keywords. Revision TKA, metal cone, allograft, bone defect. For any figures or tables, please contact authors directly

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1

Treatment of segmental bone defects remains a major clinical problem, and innovative strategies are often necessary to successfully reconstruct large volumes of bone. When fractures occur, the resulting hematoma serves as a reservoir for growth factors and a space for cell infiltration, both crucial to the initiation of bone healing. Our previous studies have demonstrated very clear ultrastructural differences between fracture hematomas formed in normally healing fractures and those formed in segmental bone defects. However, there is little information available regarding potential differences in the underlying gene expression between hematomas formed in normal fractures, which usually heal by themselves, and segmental bone defects, which do not. Therefore, the aim of this study was to identify differences in gene expression within hematomas collected from 0.5 mm (normal fracture) and 5 mm (segmental bone defect) fracture sites during the earliest stages of bone healing. Osteotomies of 0.5 and 5 mm in the femur of Fisher 344 rats were stabilized with external fixators (RISystem AG). After 3 days the rats were sacrificed, and the fracture hematomas were collected for RNA-sequencing. Ingenuity pathway analysis (IPA) was used to identify upstream regulators and biological functions that were significantly enriched with differentially expressed genes from the RNA-sequencing analysis. Animal procedures were conducted following the IACUC protocol of the UT Health Science Center San Antonio. Key upstream regulators of bone formation were less active (e.g. TGFB1, FGF2, SMAD3) or even inhibited (e.g. WNT3A, RUNX2, BMP2) in non-healing defects when compared to normally healing fractures. Many upstream regulators that were uniquely enriched in healing defects were molecules recently discovered to have osteogenic effects during fracture healing (e.g. GLI1, EZH2). Upstream regulators uniquely enriched in non-healing defects were mainly involved in an abnormal modulation of hematopoiesis, revealing evidence of impaired maturation of functional macrophages and cytokines (e.g. IL3, CEBPE), both essential for successful bone healing. In addition, the enrichment pattern suggested a dysregulation of megakaryopoiesis (e.g. MRTFA, MRTFB, GATA2), which directly affects platelet production, and therefore fracture hematoma formation. Remarkably, the organization of the ECM was the most significantly enriched biological function in the normally healing fractures, and implies that the defect size directly affected the structural properties within the fracture hematoma. Conversely, genes encoding important ECM components (e.g. BGN, various collagens, IBSP, TNC), cell adhesion molecules, MMPs (MMP2), and TIMPs were all significantly downregulated in non-healing defects. Our most recent findings reveal new important key molecules that regulate defect size-dependent fracture healing. Combined with our previous results, which identified structural differences in fracture hematomas from both types of defects, current findings indicate that differential expression of genes is dictated by the structural properties of the hematomas formed during early fracture healing. Consequently, creating a bioscaffold that mimics the structure of normal fracture hematomas could be the first step towards developing new orthoregenerative treatment strategies that potentiate healing of large bone defects and non-healing fractures

Purpose. The aim of this study was to assess the clinical and radiological result of the usage of chip bone graft in non-contained type bone defect in primary or revision total knee arthroplasty patients. Subjects and Methods. We investigated 32 patients who had underwent primary or revision total knee arthroplasty from March, 2014 to February, 2017 in our hospital, who had non-contained type of defect. The mean age was 73.1 years. 5 of them were males, while 27 of them were females. 7 of them were primary total knee arthroplasty patients, while 25 of them were revision patients. 8 of them had chip bone graft used both in the femur and tibia. 9 of them had chip bone graft used only in the tibia. The other 15 had chip bone graft used only in the femur. Wire-mesh was used in the 9 patients who had chip bone graft used only in the medial side of the tibia. We used KOOS (Knee injury and osteoarthritis outcome score), HSS (Hospital for Special Surgery knee service rating system) and WOMAC scores to assess the clinical result, before the surgery and at the last follow-up. In addition, we had follow-up x-rays and 3D CT done for the patients to check the mean bone union period. In addition, overall radiologic imaging studies were used for complications such as loosening, osteolysis and lesions with radiolucency. Result. The Mean follow-up period was 2.7 years (range; 2.1 to 5). The Mean preoperative KOOS was 102.8 (range; 47 to 132), while it became 31.8 postoperatively (range; 20 to 45). The mean HSS was 13.1 (range; 6 to 35), while it became 35.9 postoperatively (range; 24 to 64). The mean WOMAC was 82.9 (range; 62 to 92), while it became 22.5 postoperatively (range; 13 to 30). According to follow-up x-ray and CT, the mean bone union period was 10.6 months (range: 10 to 13). In follow-up 3D CT of all cases, we could check cortical healing and new bone formation, seen as medium to high-attenuating conglomerate. The graft-host junction showed trabecular ingrowth, while the medullary canal showed fibrous ingrowth. Radiologically, there was no complication such as loosening, osteolysis, migration and radiolucent lines around the stems or cement mantles. In addition, there was no complication such as infection. Conclusion. Chip bone graft is not a commonly used method for bone defect in total knee arthroplasty. According to the result of the usage of chip bone graft in primary or revision total knee arthroplasty with non-contained type of bone defect, it showed favorable result for the subject patients. Therefore, we can consider it as one of the effective methods to manage non-contained bone defect in knee arthroplasty. Keywords. Revision TKA, chip bone graft, wire-mesh, non-contained bone defect. For any figures or tables, please contact authors directly

Successful reconstruction of bone defects requires an adequate filling material that supports regeneration and formation of new bone within the treated defect in an optimal fashion. Currently available synthetic bone graft substitutes cannot fulfill all requirements of the highly complex biological processes involved in physiological bone healing. Due their unphysiologically asynchronous biodegradation properties, their specific foreign material-mediated side effects and complications and their relatively modest overall osteogenic potential, their overall clinical performance typically lags behind conventional bone grafts of human origin. However, defect- and pathology specific combination of synthetic bone graft substitutes exhibiting appropriate carrier properties with therapeutic agents and/or conventional bone graft materials allows creation of biologically enhanced composite constructs that can surpass the biological and therapeutic limits even of autologous bone grafts. This presentation introduces a bone defect reconstruction concept based on biological enhancement of optimal therapeutic agent-carrier composites and provides a rationale for an individual, requirement-specific adaptation of a truly patient-specific reconstruction of bone defects. It represents the pinnacle of the bone defect reconstruction pyramid, founded on the basic principles and prerequisites of complete elimination of the underlying pathology, preservation, augmentation or restoration of mechanical stability of the treated bone segment and creation of a biodegradable scaffold with adequate mechanical integrity. It summarises the current body of relevant experimental and clinical research, presents clinical case examples illustrating the various aspects of the proposed concept as well as early clinical results. The author hopes that the theoretical and conceptual framework provided, will help guide future research as well as clinical decision making with respect to this particular field

Introduction. Cancellous and cortical bone used as a delivery vehicle for antibiotics. Recent studies with cancellous bone as an antibiotic carrier in vitro and in vivo showed high initial peak concentrations of antibiotics in the surrounding medium. However, high concentrations of antibiotics can substantially reduce osteoblast replication and even cause cell death. Objectives. To determine whether impregnation with gentamycine impair the incorporation of bone allografts, as compared to allografts without antibiotic. Materials and method. Seventy two healthy rabbits (24 rabbits in each group) were used for this study. Bone defects (3-mm diameter, 10-mm depth) were created in the femur. Human femoral head prepared according to the Marburg bone bank system was used as bone allograft. In the experimental groups, in 1 group - the defects were filled with bone allografts, in 2 group – Perforated Gentamycin-impregnated bone allografts. The control group did not receive any filling. The animals were killed after 14, 30 and 60 days. Evaluations consisted of X-ray plain radiography, histology at 14-, 30- and 60-days post-surgery. Results. Active osteoblast activity and active formation of new bones were detected around the defect area in all groups, but the amount of new bone formation was greater in the experimental groups than the control group. We found no statistically significant differences in the rate of bone formation between 1 and 2 groups at 14, 30 and 60 days in any of the parameters studied. X-ray results showed no significant difference in bony callus formation around allografts in 1 and 2 groups. In contrast, no significant callus formation was observed in the control group. Conclusion. The use of gentamycin-impregnated bone allografts may be of value in procedures performed at the site of osteomyelitis which require a second stage reconstruction with impacted bone grafting techniques

Acetabular reconstruction of extensive bone defect is troublesome in revision total hip arthroplasty (rTHA). Kerboull or Kerboull type reinforcement acetabular device with allobone grafting has been applied since 1996. Clinical results of the procedure were evaluated. Patients. One hundred and ninety-two consecutive revision total hip arthroplasties were performed with allograft bone supported by the Kerboull or Kerboull type reinforcement acetabular device from 1996 to 2009. There were 23 men and 169 women. Kerboull plates were applied to 18 patients, and Kerboull type plates to 174. The mean follow up of the whole series was 8 years (4–18years). Surgical Technique. The superior bone defect was reconstructed principally by a large bulky allo block with plate system. Medial bone defect was reconstructed by adequate bone chips and/or sliced bone plates. After temporally fixation of bulky bone block with two 2.0mm K-wires, it was remodeled by reaming to fit the gap between host bone and plate, followed by fixation to the iliac bone by screws. Finally, residual space of the defect between host bone and the fixed plated was filled up with morselized cancellous bones, bone chips, and/or wedged bony fragments with impaction. This method was sufficiently applicable to AAOS Typeâ�, II, and III bone defects. In case of AAOS Typeâ�£, the procedure was also available after repairing discontinuation between distal and proximal bones by reconstrusion plate or allografting with tibial bone plates or sliced femoral head. Results. Nine patients (4.7%) required revision surgery (infection 5, breakage 3, and malalignment 1). The plate breakage was observed in 8 joints (4.2%). Three patients had no symptoms after the breakage. Three required revision, but the other cases were carefully observed without additional surgical intervention. Ten-year survival rate by Kaplan-Meier method was 96.6% when the endpoint was set revision by asceptic loosning. Conclusions. This study indicated that acetabular allograft reconstructions reinforced by Kerboull or Kerboull type acetabular device were able to recover bone stock with anatomic reconstruction of femoral head center, thus providing satisfactory clinical results in middle term period

This article is based on the analysis of surgical treatment peculiarities of 641 patients with post-osteomyelitis long bones defects. The average age of patients at the time of hospital admission was 32,4 ± 0,7 and ranged from 4 to 70 years. Most of them were people of active working age (476 (74.3%)) and male (523 (81.1%)). In this observation group 566 (88.3%) patients had the osteomyelitis process of the traumatic origin, including post-surgical (n = 155) and post-gunshot injuries (n = 13). Chronic hematogenous osteomyelitis was diagnosed in 75 (11.7%) patients. Most patients had lower extremity bones problems, including 444 tibia defects and 142 femoral bone defects. Much fewer patients had the osteomyelitis process of the upper extremity (humerus, radius, ulnar bone – 18, 19 and 18 respectively). Purulent necrotic process was accompanied by nonunion bone fragments in 160 (24%) patients, delayed union in 95 (14.6%) patients, false joint in 178 (27.6%) patients, segmental bone defect in 75 (11 5%) patients and bones union with edge defects and cavities in 143 (22.3%) patients. 340 (53%) patients were operated using the method of free bone grafting, and 301 (47%) patients were operated using the distraction method. The need to use the bilocal for external fixation on upper extremities occurs quite seldom (twice in our observations). Even when there is an upper extremity bone defect of several centimeters the preference should be given not to bilocal external fixation. When treating the lower extremities taking the above mentioned into consideration, segmental defects predominated, that is why the bilocal distraction-compression method of surgical treatment prevailed (98.6%). Thus, the main method of upper extremities long bones defects replacement is free bone grafting with segment fixation by the external fixation device, for lower extremities the is not-free main Ilizarov method, which allows to get positive results in 84.6% of patients with femoral bone problems and in 96.4% of tibia problems, mainly due to one-step treatment, directed simultaneously to inflammatory process elimination and maximum possible anatomical and functional restoration of the affected extremity

Introduction. The bone defect reconstruction is the first step of successful primary or revision TKA in case of large bone defect. If the defect is not reconstructed adequately, we can neither preserve knee joint function nor guarantee long survival of the implant. Allogeneic bone graft is known to be the treatment of choice in large defect. However the surgical technique is demanding and incorporation failure is constant issue of the allogeneic bone graft. We propose new bone defect reconstruction technique using multiple screws and cement. Material and method. From April 2012 to April 2014, 12 patients with large defect which could not be reconstructed with metal augment were involved in this study. The bone defect type was 10 cases of 2A and 2 cases of 2B according to AORI (Anderson Orthopedic Research Institute) classification. The defect was reconstructed with multiple screws and cementing technique by single surgeon (WS Cho). Average follow-up period was 15 months. (24 ∼ 1 month). Result. We analyzed 6 patients whose follow-up periods were more than 12 months. Average ROM was 107' and clinical scores were 86 by HSS, 93 by KS and 11 by WOMAC respectively. No complications such as infection and loosening were developed. Mean surgical time was 1 hour and 57 minutes. Conclusion. In short term follow-up, cementing technique using multiple screws can be a solution for large bone defect reconstruction

We report the results of 79 patients (81 hips) who underwent impaction grafting at revision hip replacement using the Exeter femoral stem. Their mean age was 64 years (31 to 83). According to the Endoklinik classification, 20 hips had a type 2 bone defect, 40 had type 3, and 21 had type 4. The mean follow-up for unrevised stems was 10.4 years (5 to 17). . There were 12 re-operations due to intra- and post-operative fractures, infection (one hip) and aseptic loosening (one hip). All re-operations affected type 3 (6 hips) and 4 (6 hips) bone defects. The survival rate for re-operation for any cause was 100% for type 2, 81.2% (95% confidence interval (CI) 67.1 to 95.3) for type 3, and 70.8% (95% CI 51.1 to 90.5) for type 4 defects at 14 years. The survival rate with further revision for aseptic loosening as the end point was 98.6% (95% CI 95.8 to 100). The final clinical score was higher for patients with type 2 bone defects than type 4 regarding pain, function and range of movement. Limp was most frequent in the type 4 group (p < 0.001). The mean subsidence of the stem was 2.3 mm (. sd. 3.7) for hips with a type 2 defect, 4.3 mm (. sd. 7.2) for type 3 and 9.6 mm (. sd.  10.8) for type 4 (p = 0.022). The impacted bone grafting technique has good clinical results in femoral revision. However, major bone defects affect clinical outcome and also result in more operative complications

Objectives. To compare the therapeutic potential of tissue-engineered constructs (TECs) combining mesenchymal stem cells (MSCs) and coral granules from either Acropora or Porites to repair large bone defects. Materials and Methods. Bone marrow-derived, autologous MSCs were seeded on Acropora or Porites coral granules in a perfusion bioreactor. Acropora-TECs (n = 7), Porites-TECs (n = 6) and bone autografts (n = 2) were then implanted into 25 mm long metatarsal diaphyseal defects in sheep. Bimonthly radiographic follow-up was completed until killing four months post-operatively. Explants were subsequently processed for microCT and histology to assess bone formation and coral bioresorption. Statistical analyses comprised Mann-Whitney, t-test and Kruskal–Wallis tests. Data were expressed as mean and standard deviation. Results. A two-fold increaseof newly formed bone volume was observed for Acropora-TECs when compared with Porites-TECs (14 . sd. 1089 mm. 3. versus 782 . sd. 507 mm. 3. ; p = 0.09). Bone union was consistent with autograft (1960 . sd. 518 mm. 3. ). The kinetics of bioresorption and bioresorption rates at four months were different for Acropora-TECs and Porites-TECs (81% . sd. 5% versus 94% . sd. 6%; p = 0.04). In comparing the defects that healed with those that did not, we observed that, when major bioresorption of coral at two months occurs and a scaffold material bioresorption rate superior to 90% at four months is achieved, bone nonunion consistently occurred using coral-based TECs. Discussion. Bone regeneration in critical-size defects could be obtained with full bioresorption of the scaffold using coral-based TECs in a large animal model. The superior performance of Acropora-TECs brings us closer to a clinical application, probably because of more suitable bioresorption kinetics. However, nonunion still occurred in nearly half of the bone defects. Cite this article: A. Decambron, M. Manassero, M. Bensidhoum, B. Lecuelle, D. Logeart-Avramoglou, H. Petite, V. Viateau. A comparative study of tissue-engineered constructs from Acropora and Porites coral in a large animal bone defect model. Bone Joint Res 2017;6:208–215. DOI: 10.1302/2046-3758.64.BJR-2016-0236.R1

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

In therapeutic bone repairs, autologous bone grafts, conventional or vascularized allografts, and biocompatible artificial bone substitutes all have their shortcomings. Tissue engineering may be an alternative for cranial bone repair. Titanium (Ti) and its alloys are widely used in many clinical devices because of perfect biocompatibility, highly corrosion resistance and ideal physical properties. An important progress in treating bone defects has been the introduction of bone morphogenetic proteins (BMPs), specifically BMP-2. The proteins induce osteogenic cell differentiation in vitro, as well as bone defect healing in vivo. In this study, we fabricated the titanium plate with dioxide creating by microarc oxidation (MAO) and then electronic deposition of Ca.P that can carrier recombinant human bone morphogenetic protein-2 (rhBMP-2) to enhance osteogenesis in vitro and bone formation in vivo. The rhBMP-2 was controlled released from MAO-Ca.P-rhBMP2 implant was maintain within 35days longer than Ti without MAO modification group and without CaP electronic deposition group. In addition, the in vitro results revealed that the bioactivity of rhBMP-2 released from MAO-Ca.P-rhBMP2 implant with an ideal therapeutic dose was well maintained. In vivo, the critical-sized defect (20-mm diameter) of New Zealand White rabbits was used to experiment. We concluded that sustained controlled-release of rhBMP-2 above a therapeutic dose could induce osseointegration between the implant and surrounding bone the rate of bone formation into the implant and produce neovascularization. Our study combined the concept of osteoconductive and osteoinductive to do the bone tissue regeneration

Introduction: Filling bone defects with Polymethylmetaacrylate (PMMA) has been a easy, safe and reliable technique for past four decade. Newly developed Calcium Phosphate Paste (CPP) is a mixture of alpfa Tri Calcium Phsphate (TCP), Tetra Calcium Phosphate, Calcium Hydrogen Phosphate and Hydroxyapatite. This paste hardens in 10 minutes and its stffness increases to 80Mpa in seven days. It generates no heat, no gas and requires no organic solvents. In process of hardening, the TCP structure changes to Hydroxyapatite. Materials and methods: We have used CPP in two TKA cases associate with bone defect, and 14 fracture cases. In a MRSA infected revision TKA case, reconstruction was performed with PMMA-VCM articulated spacers, and they was fixed to bone with CPP-VCM. MRSA infection has been well controlled and weight bearing could be done in 10 days after surgery. In another TKA case, large bone necrosis in femoral condyle was filled with CPP and Cementless inplant were placed on it. Seven days later, this patient could walk with a cane. Results: CPP filled in bones were not absorbed for a year, and exess CPP in soft tissue were absorbed in several weeks. In 16 cases no side effects were observed during as long as one year. Conclusion: Handling CPP is much easier than Hydroxyapatite brick or granule. CPP can be useful for total joint arthroplasty, especially in large bone defect or infected cases. It can replace a part of PMMA as a bone cement for implants in the near future

We carried out a systematic review of the literature to evaluate the evidence regarding the clinical results of the Ilizarov method in the treatment of long bone defects of the lower limbs. Only 37 reports (three non-randomised comparative studies, one prospective study and 33 case-series) met our inclusion criteria. Although several studies were unsatisfactory in terms of statistical heterogeneity, our analysis appears to show that the Ilizarov method of distraction osteogenesis significantly reduced the risk of deep infection in infected osseous lesions (risk ratio 0.14 (95% confidence interval (CI) 0.10 to 0.20), p < 0.001). However, there was a rate of re-fracture of 5% (95% CI 3 to 7), with a rate of neurovascular complications of 2.2% (95% CI 0.3 to 4) and an amputation rate of 2.9% (95% CI 1.4 to 4.4).The data was generally not statistically heterogeneous. Where tibial defects were > 8 cm, the risk of re-fracture increased (odds ratio 3.7 (95% CI 1.1 to 12.5), p = 0.036). . The technique is demanding for patients, illustrated by the voluntary amputation rate of 1.6% (95% CI 0 to 3.1), which underlines the need for careful patient selection. Cite this article: Bone Joint J 2013;95-B:1673–80

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

In severe cases of total knee & hip arthroplasty, where off-the-shelf implants are not suitable (i.e., in cases with extended bone defects or periprosthetic fractures), 3D-printed custom-made knee & hip revision implants out of titanium or cobalt-chromium alloy represent one of the few remaining clinical treatment options. Design verification and validation of such custom-made implants is very challenging. Therefore, a methodology was developed to support surgeons and engineers in their decision on whether a developed design is suitable for the specific case. A novel method for the pre-clinical testing of 3D-printed custom-made knee implants has been established, which relies on the biomechanical test and finite element analysis (FEA) of a comparable clinically established reference implant. The method comprises different steps, such as identification of the main potential failure mechanism, reproduction of the biomechanical test of the reference implant via FEA, identification of the maximum value of the corresponding FEA quantity of interest at the required load level, definition of this value as the acceptance criterion for the FEA of the custom-made implant, reproduction of the biomechanical test with the custom-made implant via FEA, decision making for realization or re-design based on the acceptance criterion is fulfilled or not. Exemplary cases of custom-made knee & hip implants were evaluated with this new methodology. The FEA acceptance criterion derived from the reference implants was fulfilled in both custom-made implants and subsequent biomechanical tests verified the FEA results. The suggested method allows a quantitative evaluation of the biomechanical properties of custom-made knee & hip implant without performing physical bench testing. This represents an important contribution to achieve a sustainable patient treatment in complex revision total knee & hip arthroplasty with custom-made 3D printed implants in a safe and timely manner

A seventy-one-years old, female, has been treated by hemodialysis from 1977 due to renal failure. In April 19, 1985, she had Charnley Low Friction Arthroplasty for right hip joint. She often felt mild pain on the joint from 2000. Radiograph showed central migration of the socket and huge cystic bone defect of the acetabulum surrounded by thin cortical bone like an egg-shell form. Tear drop (acetabular floor) was diminished due to massive bone destruction or severe osteolysis. CT showed that the diameter of the cavity was approximately 10 cm. In March 1, 2002, the socket was upside down and moving freely in the cavity. The patient could not weight-bear on right lower extremity but walk without two crutches. Hemiarthroplasty for her left hip joint (contra-lateral side) was done in June 26, 2006, due to femoral neck fracture. Because of continuous right hip joint pain and walking disturbance, she underwent revision surgery in May 20, 2008. At the surgery, the cavity was empty except for the socket and fibrous tissue. Impaction grafting by using morselized allograft including porous and solid hydroxyapatite granules (100 g and 40 g each) was done after the socket and the tissue were extracted. A custom made all polyethylene socket (73 × 68 mm in diameter) was fixed by polymethylmetacrylate bone cement. Postoperative course was uneventful. She can walk with one crutch and ride on/off a vehicles without help four months postoperatively. It is often difficult to reconstruct acetabulum with large bone defect in revision total hip arthroplasty. Especially, almost of support rings with hook cannot be applied in the case that the tear drop is destructive or absorbed. Impaction bone grafting is commonly used for reconstruction of bone defect in revision surgery. However, the extremely thick graft for large bone defect is at risk of collapsing lead to implant migration. The socket used in the case was custom made jumbo type to reduce the thickness of impaction grafting. It seems to be one of resolution to use the custom made jumbo socket for the case with large defect of acetabulum in revision total hip Arthroplasty

Introduction. Revision total knee arthroplasty (TKA) has been often used with a metal block augmentation for patients with poor bone quality. However, bone defects are frequently detected in revision TKA used with metal block augmentation. This study focused on identification of a potential possibility of the bone defect occurrence through the evaluation of the strain distribution on the cortical bone of the tibia implanted revision TKA with metal block augmentation, during high deep flexion. Materials and Methods. Composite tibia finite element (FE) model was developed and revision TKA FE model with a metal block augmentation (Baseplate size #5 44AP/67ML, Spacer size #5 44AP/67ML, Stem size Φ9, L30, Augment #5 44AP/67ML thickness 5mm) was integrated with the composite tibia FE model. 0°, 30° 60°, 90°, 120° and 140° flexion positions were then considered with femoral rollback phenomenon [Fig 1.A]. A compressive load of 1,600N through the femoral component was applied to the composite tibia FE model integrated with the tibia component, sharing by the medial and lateral condyles, simulating a stance phase before toe-off [Fig 1.B]. Results and Discussions. The strain distribution on the cortical bone of the tibia was shown in [Fig 2]. The results showed that the strains on the posterior region were gradually increased from extension to high deep of the knee joint and generally larger than the other regions. This fact was favorably corresponded to the femoral rollback phenomenon in the knee joint, showing a good accuracy of our FE model. In contrast to the results on the posterior region, the strains on the medial region were gradually decreased after 60° or 90° flexion position and relatively lower than the other regions. Particularly, the strains on the medial region were generally lower than 50–100 µstrain, which is known as critical value range able to inducing bone loss, during high deep flexion. This fact indicate that a potential possibility of bone defect occurrence in revision TKA used with a metal block augmentation may be relatively increased in patients who are frequently exposed to a personal lifestyle history with the loading conditions of the high flexion. This study may be valuable by identifying for the first time a potential possibility of the bone defect occurrence through evaluation of the strain distribution beneath metal block augmentation in revision TKA used with a metal block augmentation during high deep flexion. Conclusions. A potential possibility of bone defect occurrence in revision TKA used with a metal block augmentation may be dependent on loading patterns applied on the knee joint related to personal lifestyle history. Particularly, it may be relatively increased in patients who are frequently exposed to a personal lifestyle history with the loading conditions of the high flexion. Acknowledgements. This study was supported by a grant from the New Technology Product Evaluation Technical Research project, Ministry of Food and Drug Safety (MFDS), Republic of Korea

Introduction and Objective. In recent years, along with the extending longevity of patients and the increase in their functional demands, the number of annually performed RSA and the incidence of complications are also increasing. When a complication occurs, the patient often needs multiple surgeries to restore the function of the upper limb. Revision implants are directly responsible for the critical reduction of the bone stock, especially in the shoulder. The purpose of this paper is to report the use of allograft bone to restore the bone stock of the glenoid in the treatment of an aseptic glenoid component loosening after a reverse shoulder arthroplasty (RSA). Materials and Methods. An 86-years-old man came to our attention for aseptic glenoid component loosening after RSA. Plain radiographs showed a complete dislocation of the glenoid component with 2 broken screws in the neck of glenoid. CT scans confirmed the severe reduction of the glenoid bone stock and critical bone resorption and were used for the preoperative planning. To our opinion, given the critical bone defect, the only viable option was revision surgery with restoration of bone stock. We planned to use a bone graft harvested from distal bone bank femur as component augmentation. During the revision procedure the baseplate with a long central peg was implanted “on table” on the allograft and an appropriate osteotomy was made to customize the allograft on the glenoid defect according to the CT-based preoperative planning. The Bio-component was implanted with stable screws fixation on residual scapula. We decided not to replace the humeral component since it was stable and showed no signs of mobilization. Results. The new bio-implant was stable, and the patient gained a complete functional recovery of the shoulder. The scheduled radiological assessments up to 12 months showed no signs of bone resorption or mobilization of the glenoid component. Conclusions. The use of bone allograft in revision surgery after a RSA is a versatile and effective technique to treat severe glenoid bone loss and to improve the global stability of the implant. Furthermore, it represents a viable alternative to autologous graft since it requires shorter operative times and reduces graft site complications. There are very few data available regarding the use of allografts and, although the first studies are encouraging, further investigation is needed to determine the biological capabilities of the transplant and its validity in complex revisions after RSA

Purpose. Angiogenesis and osteogenesis are essential for bone growth, fracture repair, and bone remodeling. VEGF has an important role in bone repair by promoting angiogenesis and osteogenesis. In our previous study, endothelial progenitor cells (EPCs) promoted bone healing in a rat segmental bone defect as confirmed by radiological, histological and microCT evaluations (Atesok, Li, Schemitsch 2010); EPC treatment of fractures resulted in a significantly higher strength by biomechanical examination (Li, Schemitsch 2010). In addition, cell-based VEGF gene transfer has been effective in the treatment of segmental bone defects in a rabbit model (Li, Schemitsch et al 2009); Purpose of this study: Evaluation of VEGF gene expression after EPC local therapy for a rat segmental bone defect. Method. Rat bone marrow-derived EPCs were isolated from the rat bone marrow by the Ficoll-paque gradient centrifuge technique. The EPCs were cultured for 7 to 10 days in endothelial cell growth medium with supplements (EGM-2-MV-SingleQuots, Clonetics). and collected for treatment of the rat segmental bone defect. EPCs were identified by immunocytochemistry staining with primary antibodies for CD34, CD133, FLK-1, and vWF. A total of fifty six rats were studied. A five millimeter segmental bone defect was created in the middle 1/3 of each femur followed by mini plate fixation. The treatment group received 1×106 EPCs locally at the bone defect and control animals received saline only. Seven control and seven EPC treated rats were included in each group at 1, 2, 3 and 10 weeks. Animals were sacrificed at the end of the treatment period, and specimens from the fracture gap area were collected and immediately frozen. Rat VEGF mRNA was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantified by VisionWorksLS. All measurements were performed in triplicate. Results. Cultured EPCs at 1 week showed positive staining for CD34, CD133, Flk-1 and vWf markers. The EPC group had a greater VEGF expression than the control group at week 1, 2 and 3 but not at week 10. Three VEGF isoforms were detected in this rat model: VEGF120, VEGF164 and VEGF188. VEGF120 and VEGF164 levels peaked at two weeks, while VEGF188 levels peaked at three weeks. All three VEGF isoform levels were low at ten weeks. Conclusion. EPC-based therapy for a segmental bone defect results in increased VEGF expression during the early period of fracture repair. In addition, the specific VEGF isoform may be a key regulator of the bone healing process. These findings demonstrate that EPCs promote fracture healing by increasing VEGF levels and thus stimulating angiogenesis, a process that is essential for early callus formation and bone regeneration

The current ‘gold’ standard surgical intervention for critical size bone defect repair involves autologous bone grafting, that risks inadequate graft containment and soft tissue invasion. Here, a new regenerative strategy was explored, that uses a barrier membrane to contain bone graft. The membrane is designed to prevent soft tissue ingrowth, whilst supporting periosteal regrowth, an important component to bone regeneration. This study shows the development of a collagen-based barrier membrane supportive of periosteal-derived mesenchymal stem cell (P-MSC) growth. P-MSC-homing barrier membranes were successfully obtained with nonaligned fibres, via free-surface electrospinning using type I collagen and poly(E-caprolactone) in 1,1,1,3,3,3-Hexafluoro-2-propanol. Introduction of collagen in the electrospinning mixture was correlated with decreased mean fibre diameter (d: 319 nm) and pore size (p: 0.2–0.6 μm), with respect to collagen-free membrane controls (d: 372 nm; p: 1–2 μm). Consequently, as the average MSC diameter is 20 μm, this provides convincing evidence of the creation of a MSC containment membrane. SEM-EDX confirmed Nitrogen and therefore collagen fibre localisation. Quantification of collagen content, using Picro Sirius Red dye, showed a 50% reduction after 24 hours (PBS, 37 °C), followed by a drop to 25% at week 3. The collagen-based membrane has a significantly higher elastic modulus compared to collagen-free control membranes. P-MSCs attached and proliferated when grown onto collagen-based membranes, imaged using confocal microscopy over 3 weeks. A modified transwell cell migration assay was developed, using MINUSHEET® tissue carriers to assess barrier functionality. In line with the matrix architecture, the collagen-based membrane proved to prevent cell migration (via confocal microscopy) in comparison to the migration facilitating positive control. The aforementioned results obtained at molecular, cellular and macroscopic scales, highlight the applicability of this barrier membrane in a new ‘hybrid graft’ regenerative approach for the surgical treatment of critical size bone defects

In a rabbit model we investigated the efficacy of a silk fibroin/hydroxyapatite (SF/HA) composite on the repair of a segmental bone defect. Four types of porous SF/HA composites (SF/HA-1, SF/HA-2, SF/HA-3, SF/HA-4) with different material ratios, pore sizes, porosity and additives were implanted subcutaneously into Sprague-Dawley rats to observe biodegradation. SF/HA-3, which had characteristics more suitable for a bone substitite based on strength and resorption was selected as a scaffold and co-cultured with rabbit bone-marrow stromal cells (BMSCs). A segmental bone defect was created in the rabbit radius. The animals were randomised into group 1 (SF/HA-3 combined with BMSCs implanted into the bone defect), group 2 (SF/HA implanted alone) and group 3 (nothing implanted). They were killed at four, eight and 12 weeks for visual, radiological and histological study. The bone defects had complete union for group 1 and partial union in group 2, 12 weeks after operation. There was no formation of new bone in group 3. We conclude that SF/HA-3 combined with BMSCs supports bone healing and offers potential as a bone-graft substitute

The Masquelet or induced membrane technique (IMT) is a two-stage surgical procedure used for the treatment of segmental bone defects. In this technique, the defect is first filled with a polymethyl methacrylate (PMMA) spacer, which triggers the formation of a membrane that will encapsulate the defect. During the second surgery, the spacer is carefully removed and replaced by autologous bone graft while preserving the membrane. This membrane is vascularized, contains growth factors, and provides mechanical stability to the graft, all of which are assumed to prevent graft resorption and promote bone healing. The technique is gaining in popularity and several variations have been introduced in the clinical practice. For instance, orthopaedic surgeons now often include antibiotics in the spacer to treat or prevent infection. However, the consequences of this approach on the properties of the induce membrane are not fully understood. Accordingly, in a small animal model, this study aimed to determine the impact on the induced membrane of impregnating spacers with antibiotics frequently used in the IMT. We surgically created a five-mm segmental defect in the right femur of 25 adult male Sprague Dawley rats. The bone was stabilized with a plate and screws before filling the defect with a PMMA spacer. Animals were divided into five equal groups according to the type and dose of antibiotics impregnated in the spacer: A) no antibiotic (control), B) low-dose tobramycin (1.2 g/40 g of PMMA), C) low-dose vancomycin (1 g/40 g of PMMA), D) high-dose tobramycin (3.6 g/40 g of PMMA), E) high-dose vancomycin (3 g/40 g of PMMA). The animals were euthanized three weeks after surgery and the induced membranes were collected and divided for analysis. We assessed the expression of selected genes (Alpl, Ctgf, Runx2, Tgfb1, Vegfa) within the membrane by quantitative real-time PCR. Moreover, frozen sections of the specimens were used to quantify vascularity by immunohistochemistry (CD31 antigen), proliferative cells by immunofluorescence (Ki-67 antigen), and membrane thickness. Microscopic images of the entire tissue sections were taken and analyzed using FIJI software. Finally, we measured the concentration of vascular endothelial growth factor (VEGF) in the membranes by ELISA. No significant difference was found among the groups regarding the expression of genes related to osteogenesis (Alpl, Runx2), angiogenesis (Vegfa), or synthesis of extracellular matrix (Ctgf, Tgfb1) (n = four or five). Similarly, the density of proliferative cells and blood vessels within the membrane, as well as the membrane thickness, did not vary substantially between the control, low-dose, or high-dose antibiotic groups (n = four or five). The concentration of VEGF was also not significantly influenced by the treatment received (n = four or five). The addition of tobramycin or vancomycin to the spacer, at the defined low and high doses, does not significantly alter the bioactive characteristics of the membrane. These results suggest that orthopaedic surgeons could use antibiotic-impregnated spacers for the IMT without compromising the induced membrane and potentially bone healing

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

Bone allograft is the most widely accepted approach in treating patients suffering from large segmental bone defect regardless of the advancement of synthetic bone substitutes. However, the long-term complications of allograft application in term of delayed union and nonunion were reported due to the stringent sterilization process. Our previous studies demonstrated that the incorporation of magnesium ions (Mg2+) into biomaterials could significantly promote the gene up-regulation of osteoblasts and new bone formation in animal model. Hence, our group has proposed to establish an Mg2+ enriched tissue microenvironment onto bone allograft so as to enhance the bone healing. The decellularization and gamma irradiation process were performed on bovine bone allograft and followed by magnesium plasma treatment. To evaluate the biocompatibility and bioactivity, materials characterizations, in vitro and in vivo studies were conducted, respectively. Mg composite layer on bone surface ranged from 500nm to ∼800nm thick. The cell viability on magnesium enriched allograft was significantly higher than that of the control. The ALP gene expression of hTMSCs in the group of PIII&D treated samples was highly up-regulated. The bone regeneration ability of Mg modified bone allograft implanted in animal model was significantly superior than the control after 2-month post-operation

The use of new megaprosthesis for massive bone loss is an option for the replacement of skeletal segments. There are several clinical scenarios that can be associated with this situation including severe trauma with multiple failed osteosynthesis with a non union or with a previous prosthetic replacement of a neighbouring joint; multiple revision of arthroplasty with or without infections or large resections of tumours. The aim of this work is to evaluate retrospectively both clinical and radiological outcomes and any complications in patients treated with megaprosthesis in SEPTIC BONE DEFECTS in our Hospital from February 2012 to January 2015. From February 2012 to January 2014 a total of 20 patients were treated with mono-and bi-articular megaprosthesis subdivided as follows: 4 proximal femur, 11 distal femur, 3 total femur, 1 total humerus and 1 proximal humerus. Clinical and serial radiographic evaluations were performed at 6 weeks, 3, 6, 12, 18 and 24 months. Blood parameters with CRP and ESR were monitored for at least 2 months. The mean follow-up of patients was about 24.4 months (range 5 months to 31 months). The mean age of the patients was 53 years (range 37–80years). Of the patients 20, 9 were female and 11 were male. The aetiology was: 11 septic non unions, 3 infected TKA, 4 infected THR and 2 infected tumor prostheses. We have evaluated retrospectively both clinical and radiological outcomes of 20 patients. They had large bone defects that threatened the viability of the limb. They were treated with megaprosthesis. Although the mean length of follow-up was only 24.4 months they showed encouraging clinical results, with good articulation of the segments, no somato-sensory or motor deficit and acceptable functional recovery. There were three cases of dislocation, one case with rifampicin toxicity, one case with acute prosthetic infection (case that needed debridement and one case with chronic oral antimicrobial. Megaprosthesis provides a valuable opportunity to restore functionality to patients with highly disabling diseases. The number of complications is not depreciable

Aim. Which patients is bone-defect-reconstruction with the Masquelet-technique suitable and which problems did we see?. Method. From 11/2011 to 4/2016 we treated 49 Patients (12f/37m) with bone-defects up to 150mm after septic complications with the Masquelet-technique. We had infected-non-unions of upper and lower extremity, chronic osteomyelitis, infected knee-arthrodesis and upper-ancle-empyema. On average the patients were 48 (8–74) years old. The mean bone-defect-size was 60 mm (25–150). From other hospitals came 47 of the 49 patient, where they had up to 20 (mean 4,9) operations caused by the infection. The time before transfer to our hospital was on average 177days (6–720). 40 patients receaved flaps because of soft tissue-defects (12 free flaps, 28 local flaps). 21 patients suffered a polytrauma. In 8 cases the femur, in 4 cases a knee-arthrodesis, in 34 cases tibia, in 2 cases humerus and in 1 case the ulna were infected resulting in bone defects. Indication for the Masquelet-technique was low-/incompliance in 35 cases due to higher grade of traumatic brain injury and polytrauma and difficult soft-tissue conditions, in 9 times problems with segment-transport and in 5 cases as dead space management. Positive microbial detection succeeded in 32 patients at the first operation. Mainly we found difficult to treat bacteria. After treating the infection with radical sequestrectomy, removal of foreign bodies and filling the defect with antibiotic loaded cement spacer and external fixation we removed the spacer6–8 weeks later and filled the defect with bone graft. In 23 cases we stabilized the defect then with an internal angle stable plate. All patients were examined clinically and radiologically every 4–6 weeks in our outpatient-department until full weight bearing, later every 3 months. Results. In 41 of 49 cases the infection was clinically treated successfully. 21 patients are allowed for full weight bearing (all with secondary internal plates). There were 8 recurrences of infection, 22 instabilities needing internal stabilization and further bone graft. We saw “Plate-breaks” in 4 cases. 2 patients underwent amputation. Conclusions. For patients with low-/incompliance for various reasons and for those with difficult soft tissue conditions following flaps the Masquelet technique is a valuable alternative to the normal bone graft and to the segment transport. The stiffness of the new Masquelet bone like a rod is a problem. Internal fixation is often necessary

Introduction. Diaphyseal bone defect represents a significant problem for orthopaedic surgeons and patients. Bone is a complex tissue whose structure and function depend strictly on ultrastructural organization of its components: cells, organic (extracellular matrix, ECM) and inorganic components. The purpose of this study was to evaluate bone regeneration in a critical diaphyseal defect treated by implantation of a magnetic scaffold fixed by hybrid system (magnetic and mechanical), supplied through nanoparticle-magnetic (MNP) functionalized with Vascular Endothelial-Growth-Factor-(VEGF) and magnetic-guiding. Methods. A critical long bone defect was created in 8 sheep metatarsus diaphysis: it was 20.0 mm in length; the medullary canal was reamed till 8.00 mm of inner diameter. Then a 8.00 mm diameter magnetic rod was fitted into proximal medullary canal (10 mm in length). After that a scaffold made of Hydroxyapatite (outer diameter 17.00 mm) that incorporates magnetite (HA/Mgn 90/10) was implanted to fill critical long bone defect. A magnetic rod (6.00 mm diameter) was firmly incorporated at proximal side into the scaffold. Both magnets had 10 mm length. To give stability to the complex bone-scaffold-bone a plate was used as a bridge; it was fixed proximally by 2 screws and distally by 3 screws. Scaffolds biocompatibility was previously assessed in vitro using human osteoblast-like cells. Magnetic forces through scaffold were calculated by finite element software (COMSOL Multiphysics, AC/DC Model). One week after surgery, magnetic nanoparticles functionalized with VEGF were injected at the mid portion of the scaffold using a cutaneous marker positioned during surgery as reference point in 4 sheep; other sheep were used as control group. After sixteen weeks, sheep were sacrificed to analyze metatarsi. Macroscopical, radiological and microCT examinations were performed. Results. Samples obtained didn't show any inflammatory tissue around the scaffold and revealed bone tissue formation inside pores of the scaffolds and we could see also complete coverage of the scaffolds. Formation of new bone tissue was more evident at magnetized bone-scaffold interface. X-rays showed a good integration of the scaffold with a good healing process of critical bone defect: new cortical bone formation seemed to be present, recreating continuity of metatarsus diaphysis. No signs of scaffold mobilization was showed (Fig. 1). All these datas were confirmed by the microCT: new bone formation inside the scaffolds was evident, in particular at proximal bone-scaffold interface, where permanent magnet were present (Fig. 2). These preliminary results lead our research to exploiting magnetic forces to stimulate bone formation, as attested in both in vitro and in vivo models and to improve fixation at bone scaffold interface, as calculated by finite element software, and moreover to guide targeted drug delivery without functionalized magnetic nanoparticles dissemination in all body

To document early in-vivo concentrations of gentamicin in plasma and drain fluid after bone defect reconstruction using a gentamicin-eluting bone graft substitute. Introduction. Reconstruction of bone defects after surgical bone tumor resection is associated with an increased risk of infection and some surgeons therefore prefer extended antibiotic prophylaxis in these patients. A gentamicin-eluting bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis(1) and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this and many other indications. We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37–79) years) who underwent bone defect reconstruction with a gentamicin-eluting bone graft substitute (CERAMENT™|G – BONESUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic bone disease (n=3, proximal humerus), giant cell tumor (n=2, distal femur), aseptic prosthetic loosening (n=1, knee) and chondroid tumor (n=1, distal femur). Additional endoprosthetic reconstruction with a tumor prosthesis was performed in 3 patients (2 proximal humerus and 1 distal femur). Drain fluid and plasma was collected immediately postoperatively and each postoperative day until the drain was removed. In 2 cases we were unable to collect drain fluid directly postoperatively due to minimal fluid production. Gentamicin concentrations were analyzed using an antibody technique (Indiko™ – Thermo Scientific). A mean of 14 (10–20) mL gentamicin-eluting bone graft substitute was used, either alone or in combination with cancellous allograft and/or a bone graft substitute not containing gentamicin (CERAMENT™|BVF – BONESUPPORT AB). Mean drain fluid concentrations of gentamicin were 1200 (723–2100) mg/L immediately postoperative (0–2 hours), 1054 (300–1999) mg/L on day 1 (17–23 hours) and 509 (38–1000) mg/L on day 2 (39–45 hours). Mean plasma concentrations of gentamicin were 1.26 (1.08–1.42) mg/L immediately postoperative, 0.95 (0.25–2.06) mg/L on day 1 and 0.56 (0.20–0.88) mg/L on day 2. Discussion. As gentamicin induces a concentration-dependent bacterial killing effect, the obviously high local peak concentrations of gentamicin found in this study would be expected to deliver a substantial prophylactic effect after long operations with an increased risk of intraoperative bacterial contamination. Local implantation of a gentamicin-eluting bone graft substitute for bone defect reconstruction results in high concentrations of gentamicin in the drain fluid in the first postoperative days and low plasma concentrations