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. 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

As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA) and collagen. Chondrocytes and mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also bioprinted to accelerate cell growth and development of ECM in bioprinted constructs. Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture, with accelerated cell growth seen with inclusion of cell spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion, we developed novel composite bioinks that can be triple-crosslinked, facilitating successful chondrocyte and MSC growth in 3D bioprinted scaffolds and in vitro repair of an osteochondral defect model. This offers hope for a new approach to treating AC defects

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

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

Aims. This study describes the use of the Masquelet technique to treat segmental tibial bone loss in 12 patients. Patients and Methods. This retrospective case series reviewed 12 patients treated between 2010 and 2015 to determine their clinical outcome. Patients were mostly male with a mean age of 36 years (16 to 62). The outcomes recorded included union, infection and amputation. The mean follow-up was 675 days (403 to 952). . Results. The mean tibial defect measured 5.8 cm (2 to 15) in length. Of the 12 patients, 11 had an open fracture. Eight underwent fixation with an intramedullary nail, three with plates and one with a Taylor Spatial Frame. The mean interval between stages was 57 days (35 to 89). Bony union was achieved in only five patients. Five patients experienced infective complications during treatment, with two requiring amputation because of severe infection. Conclusion. The Masquelet technique was relatively ineffective in achieving union in this series, and was associated with a high rate of infection. Cite this article: Bone Joint J 2017;99-B:680–5

Aims. The aims of this study were to establish whether composite fixation (rail-plate) decreases fixator time and related problems in the management of patients with infected nonunion of tibia with a segmental defect, without compromising the anatomical and functional outcomes achieved using the classical Ilizarov technique. We also wished to study the acceptability of this technique using patient-based objective criteria. Patients and Methods. Between January 2012 and January 2015, 14 consecutive patients were treated for an infected nonunion of the tibia with a gap and were included in the study. During stage one, a radical debridement of bone and soft tissue was undertaken with the introduction of an antibiotic-loaded cement spacer. At the second stage, the tibia was stabilized using a long lateral locked plate and a six-pin monorail fixator on its anteromedial surface. A corticotomy was performed at the appropriate level. During the third stage, i.e. at the end of the distraction phase, the transported fragment was aligned and fixed to the plate with two to four screws. An iliac crest autograft was added to the docking site and the fixator was removed. Functional outcome was assessed using the Association for the Study and Application of Methods of Ilizarov (ASAMI) criteria. Patient-reported outcomes were assessed using the Musculoskeletal Tumor Society (MSTS) score. Results. The mean age of patients was 38.1 years (. sd. 12.7). There were 13 men and one woman. The mean size of the defect was 6.4 cm (. sd. 1.3). the mean follow-up was 33.2 months (24 to 50). The mean external fixator index was 21.2 days/cm (. sd. 1.5). The complication rate was 0.5 (7/14) per patient. According to the classification of Paley, there were five problems and two obstacles but no true complications. The ASAMI bone score was excellent in all patients. The functional ASAMI scores were excellent in eight and good in six patients. The mean MSTS composite score was 83.9% (. sd. 7.1), with an MSTS emotional acceptance score of 4.9 (. sd. 0.5; maximum possible 5). Conclusion. Composite fixation (rail-plate) decreases fixator time and the associated complications, in the treatment of patients of infected nonunion tibia with a segmental defect. It also provides good anatomical and functional results with high emotional acceptance. Cite this article: Bone Joint J 2018;100-B:1094–9

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

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

We treated 15 patients with atrophic nonunion of a diaphyseal fracture of the humerus with an associated bony defect using an autogenous cancellous bone graft and a plate to bridge the defect. There were nine men and six women with a mean age of 48 years. The mean length of the bony defect was 3 cm. At a mean follow-up of 30 months only one fracture failed to unite. This suggests that, in the presence of a well-vascularised envelope of muscle, the application of an autogenous cancellous bone graft in conjunction with a bridging plate represents a good alternative to more demanding surgical techniques

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

Aims. Our objective was to conduct a systematic review and meta-analysis, to establish whether differences arise in clinical outcomes between autologous and synthetic bone grafts in the operative management of tibial plateau fractures. Methods. A structured search of MEDLINE, EMBASE, the online archives of Bone & Joint Publishing, and CENTRAL databases from inception until 28 July 2021 was performed. Randomized, controlled, clinical trials that compared autologous and synthetic bone grafts in tibial plateau fractures were included. Preclinical studies, clinical studies in paediatric patients, pathological fractures, fracture nonunion, or chondral defects were excluded. Outcome data were assessed using the Risk of Bias 2 (ROB2) framework and synthesized in random-effect meta-analysis. The Preferred Reported Items for Systematic Review and Meta-Analyses guidance was followed throughout. Results. Six studies involving 353 fractures were identified from 3,078 records. Following ROB2 assessment, five studies (representing 338 fractures) were appropriate for meta-analysis. Primary outcomes showed non-significant reductions in articular depression at immediate postoperative (mean difference -0.45 mm, p = 0.25, 95%confidence interval (CI) -1.21 to 0.31, I. 2. = 0%) and long-term (> six months, standard mean difference -0.56, p = 0.09, 95% CI -1.20 to 0.08, I. 2. = 73%) follow-up in synthetic bone grafts. Secondary outcomes included mechanical alignment, limb functionality, and defect site pain at long-term follow-up, perioperative blood loss, duration of surgery, occurrence of surgical site infections, and secondary surgery. Mean blood loss was lower (90.08 ml, p < 0.001, 95% CI 41.49 to 138.67) and surgery was shorter (16.17 minutes, p = 0.04, 95% CI 0.39 to 31.94) in synthetic treatment groups. All other secondary measures were statistically comparable. Conclusion. All studies reported similar methodologies and patient populations; however, imprecision may have arisen through performance variation. These findings supersede previous literature and indicate that, despite perceived biological advantages, autologous bone grafting does not demonstrate superiority to synthetic grafts. When selecting a void filler, surgeons should consider patient comorbidity, environmental and societal factors in provision, and perioperative and postoperative care provision. Cite this article: Bone Jt Open 2022;3(3):218–228

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

Aims

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

Aims. Osteopetrosis (OP) is a rare hereditary disease that causes reduced bone resorption and increased bone density as a result of osteoclastic function defect. Our aim is to review the difficulties, mid-term follow-up results, and literature encountered during the treatment of OP. Methods. This is a retrospective and observational study containing data from nine patients with a mean age of 14.1 years (9 to 25; three female, six male) with OP who were treated in our hospital between April 2008 and October 2018 with 20 surgical procedures due to 17 different fractures. Patient data included age, sex, operating time, length of stay, genetic type of the disease, previous surgery, fractures, complications, and comorbidity. Results. The mean follow-up period was 92.5 months (25 to 140). Bony union was observed in all of our patients. Osteomyelitis developed in two patients with femoral shaft fractures, and two patients had peri-implant stress fractures. Conclusion. Treatment of fractures in OP patients is difficult, healing is protracted, and the risk of postoperative infection is high. In children and young adults with OP who have open medullary canal and the epiphyses are not closed, fractures can be treated with surgical techniques such as intramedullary titanium elastic nail (TENS) technique or fixation with Kirschner (K)-wire. Cite this article: Bone Joint J 2020;102-B(8):1082–1087

Osteoinductive bone substitutes are in their developmental infancy and a paucity of effective grafts options persists despite clinical demand. Bone mineral substitutes such as hydroxyapatite cause minimal biological activity when compared to osteoinductive systems present biological growth factors in order to drive bone regeneration. We have previously demonstrated the in-vitro efficacy of a bioengineered system at presenting growth factors at ultra low-doses. This study aimed to translate this growth factor delivery system towards a clinically applicable implant. Osteoinductive surfaces were engineered using plasma polymerisation of poly(ethyl acrylate) onto base materials followed by adsorption of fibronectin protein and subsequently growth factor (BMP-2). Biological activity following ethylene oxide (EO) sterilisation was evaluated using ELISAs targeted against BMP-2, cell differentiation studies and atomic force microscopy. Scaffolds were 3D printed using polycaprolactone/hydroxyapatite composites and mechanically tested using a linear compression models to calculate stress/strain. In-vivo analysis was performed using a critical defect model in 23 mice over an 8 week period. Bone formation was assessed using microCT and histological analysis. Finally, a computer modelling process was developed to convert patient CT images into surface models, then formatted into 3D-printable scaffolds to fill critical defects. Following EO sterilisation, there was no change in scaffold surface and persistent availability of growth factors. Scaffolds showed adequate porosity for cell migration with mechanical stiffness similar to cancellous bone. Finally, the in vivo murine model demonstrated rapid bone formation with evidence of trabecular remodelling in samples presenting growth factors compared to controls

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

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

Introduction. what size of defect is optimal for creating an atrophic nonunion animal model has not been well defined. Our aim in this study was to establish a clinically relevant model of atrophic nonunion in rat femur by creation of a bone defect to research fracture healing and nonunion. Materials and methods. We used 30 male Fischer 344 rats (aged 10–11 weeks), which were equally divided into six groups. The segmental bone defects to a single femur in each rat were performed by double transverse osteotomy, and different sized defects were created by group for each group (1 mm, 2 mm, 3 mm, 4 mm, 5 mm and 6 mm). The defects were measured and maintained strictly by using an original external fixator. The periosteum for each defect was stripped both proximally and distally. Thereafter, these models were evaluated by radiology and histology. Radiographs were taken at baseline and at intervals of two weeks over a period of 8 weeks. Atrophic nonunion was defined as a lack of continuity and atrophy of both defect ends radiologically and histologically at eight weeks. Results. In the 1 mm defect group, all defects had healed. In the 2 mm group, one-fifth remained atrophic nonunion. In the 3 mm group, three-fifths had atrophic nonunion, and all of the defects of groups of 4 mm and over were atrophic nonunion. Conclusion. This study showed that we were able to predictively produce an atrophic nonunion animal model by creating defects of at least 4 mm in the Fischer 344 rat femur