Reverse total shoulder arthroplasty (RSA) with glenoid bone grafting has become a common option for the management of significant glenoid bone loss and deformity associated with glenohumeral osteoarthritis. Despite the increasing utilization of this technique, our understanding of the rates of bone graft union, complications and outcomes are limited. The objectives of this systematic review are to determine 1) the overall rate of bone graft union, 2) the rate of union stratified by graft type and technique, 3) the reoperation and complication rates, and 4) functional outcomes, including range of motion (ROM) and functional outcome scores following RSA with glenoid bone grafting. A comprehensive search of MEDLINE, Embase, and CINAHL databases was completed for studies reporting outcomes following RSA with glenoid bone grafting. Inclusion criteria included clinical studies with greater than 10 patients, and minimum follow up of one year. Studies were screened independently by two reviewers and quality assessment was performed using the MINORs criteria. Pooled and frequency-weighted means and standard deviations were calculated where applicable. Overall, 15 studies were included, including nine retrospective case series (level IV), four retrospective cohort studies (level III), one prospective cohort study (level II) and one randomized control trial (level I). The entire cohort consisted of 555 patients with a mean age of 71.9±2.1 years and 70 percent female. The mean follow-up was 33.8±9.4 months. Across all procedures, 84.9% (N=471) were primary arthroplasties, and 15.1% (N=84) were revisions. The overall graft union rate was 89.2%, but was higher at 96.1% among studies that used autograft bone (9 studies, N=308). When stratified by technique, bone graft for the purposes of lateralization resulted in a 100% union rate (4 studies, N=139), while eccentric bone grafts used in asymmetric bone loss resulted in a lower union rate of 84.9% (10 studies, N=345). The overall revision rate was 6.5%, and was lowest following primary cases at 1.8% (11 studies, N=393). The pooled mean scapular notching rate was 20.1% (12 studies, N=497). Excluding notching, the pooled mean complication rate was 21.5% for all cases and 13% for primary cases (11 studies, N=393). When reported, there was significant improvement in post-operative ROM in all planes. There was also improvement in functional outcome scores, whereby the frequency-weighted mean Constant score increased from 25.9 to 67.2 (8 studies, N=319), ASES score increased from 34.7 to 75.2 (4 studies, N=142), and SST score increased from 2.1 to 7.6 (5 studies, N=196) at final follow up. This review demonstrates that glenoid bone grafting with RSA results in good mid-term clinical and radiographic outcomes. Union rate appears to depend highly on graft type and technique, whereby the highest union rates were seen following the use of autograft bone for the purposes of lateralization. Interestingly, the union rate of autograft bone for the purposes of augmentation in eccentric bone loss is considerably lower and its impact on the long-term survivorship of the implant remains unknown

Aim. infected segmental bone defect (ISBD) is frequent in developing countries. The aim of this study was to assess the efficacy of the Masquelet technique in the treatment of ISBD in a low-resource setting. Patients and Method. We performed a prospective cohort study during the period from 2018 to 2022. Patients with infected bone defect of long bones were included. Management protocol consisted of two stages in all patients. The first stage consisted in debridement, tissues biopsy for microbiological culture, stabilization with external fixator and defect filling with gentamicin cement spacer. The second stage consisted of reconstruction using a cancellous bone autograft alone, or a mixture of autograft with allograft (demineralized bone matrix + tricalcium phosphate) and 1 gram of vancomycin powder. All patients were followed-up for at least one year. The results were assessed based on both objective (clinical and radiographic evaluation) and subjective (limb function and patient satisfaction) criteria. Main outcomes were bone union, reoperation and failure rates, union time, and limb function. Results. We included 31 patients in this study (80.6% men), with a median age of 35 [9 – 80] years. The tibia was affected in 12 cases and the femur in 15 cases. The median size of bone defect was 4 [1.5 – 12] cm. The most prevalent microorganisms were Klebsiella pneumoniae and Staphylococcus aureus. The mean interval between both stages was 14 (8 – 36) weeks and the median follow-up period after the second stage was 20 [12-62] months. External fixation was used in both stages in 25(80%) cases. Bone union was achieved in 26 (83.8%) patients of whom 24 without recurrence of infection, over a median time of 9 [6 – 16] months. All patients with a mixed graft (allograft and autograft) impregnated with local antibiotics achieved bone union. Two patients needed reoperation for relapse of infection between both stages, and subsequently achieved bone union without recurrence of infection. There were three cases of failure related to persistent infection or insufficient fixation stability in the second stage. Conclusions. Masquelet technique is a reliable procedure that can be safely performed in limited resources settings with satisfactory results. The mixture of autograft and allograft when available, all mixed with vancomycin seems to give promising results

Lumbar fusion surgery is an established procedure for the treatment of several spinal pathologies. Despite numerous techniques and existing devices, common surgical trends in lumbar fusion surgery are scarcely investigated. The purpose of this Canada-based study was to provide a descriptive portrait of current surgeons’ practice and implant preferences in lumbar fusion surgery while comparing findings to similar investigations performed in the United Kingdom. Canadian Spine Society (CSS) members were sampled using an online questionnaire which was based on previous investigations performed in the United Kingdom. Fifteen questions addressed the various aspects of surgeons’ practice: fusion techniques, implant preferences, and bone grafting procedures. Responses were analyzed by means of descriptive statistics. Of 139 eligible CSS members, 41 spinal surgeons completed the survey (29.5%). The most common fusion approach was via transforaminal lumber interbody fusion (TLIF) with 87.8% performing at least one procedure in the previous year. In keeping with this, 24 surgeons (58.5%) had performed 11 to 50 cases in that time frame. Eighty-six percent had performed no lumbar artificial disc replacements over their last year of practice. There was clear consistency on the relevance of a patient specific management (73.2%) on the preferred fusion approach. The most preferred method was pedicle screw fixation (78%). The use of stand-alone cages was not supported by any respondents. With regards to the cage material, titanium cages were the most used (41.5%). Published clinical outcome data was the most important variable in dictating implant choice (87.8%). Cage thickness was considered the most important aspect of cage geometry and hyperlordotic cages were preferred at the lower lumbar levels. Autograft bone graft was most commonly preferred (61.0%). Amongst the synthetic options, DBX/DBM graft (64.1%) in injectable paste form (47.5%) was preferred. In conclusion, findings from this study are in partial agreement with previous work from the United Kingdom, but highlight the variance of practice within Canada and the need for large-scale clinical studies aimed to set specific guidelines for certain pathologies or patient categories

Previous clinical studies have shown the efficacy of a foreign body-induced membrane combined with bone autograft for the reconstruction of traumatologic or pathologic large bone defects or, bone non union. This membrane, rich in mesenchymal stromal cells (MSC), avoids bone autograft resorption and promotes consolidation by revascularisation of the bone and secretion of growth factors. Reconstruction requires two different surgical stages: firstly, insertion of a cement spacer in the defect, and secondly, removal of the spacer, preservation of the foreign body-induced membrane and filling of the cavity by bone autograft. The optimal time to perform the second surgical stage remains unclear. So, we aimed to correlate bone healing and, phenotype and function of cells isolated from the induced membrane, in patients whose second surgery was performed on average after 6 months (i.e. beyond the recommended time of one month). Cell phenotype was determined by flow cytometry and cell function by: alkaline Phosphatase enzyme activity, secretion of calcium and von Kossa staining. Second, using histological and immunohistochemistry studies, we aimed to determine the nature and function of induced membrane over time. Seven patients were included with their consent. Results showed Treated patients achieved in all cases bone union (except for one patient) and in in vitro and histology and immunohistochemistry gave some indications which need to be completed in the future. First, patient age seemed to be an indicator of bone union speed and recurrent infection, appeared to influence in vitro MSC osteogenic potential and induced membrane structure. Second, we reported, in bone repair situation, the commitment over time in osteogenic lineage of a surprising multipotent tissue (induced membrane) able of vascularisation/ osteogenesis/ chondrogenesis at a precocious time. Finally, best time to perform the second stage (one month) could be easily exceeded since bone union occurred even at very late times

Spinal fusion is one of the most common surgical procedures in spine surgery, whose primary objective is the stabilization of the spine for the treatment of many degenerative, traumatic and oncological diseases of the spine. Autologous bone is still considered the “gold standard” technique for spinal fusion. However, biomaterials which are potentially osteogenic, osteoinductive and osteoconductive can be used to increase the process of spinal fusion. We evaluated two new bone substitutes as an alternative to autologous bone for spinal fusion, using an animal model of large size (adult sheep). A preclinical study was designed to compare the efficacy of SINTlife® Putty and DBSINT® biomaterials with conventional bone autograft in an ovine model of lumbar spine fusion. SINTlife® is a biomaterial made from hydroxyapatite enriched with magnesium ions, resulting to be very similar to natural bone. DBSint® is a paste composite bone, osteo-inductive, pliable and conformable, consisting of demineralized bone matrix (DBM) carried by hydroxyapatite biomimetics. Eighteen adult female sheep were selected for two-levels spine surgical procedures. The animals were divided in two groups: in Group A, one fusion level was treated with SINTlife® Putty and the other level received cortical-cancellous bone autograft; in Group B, one fusion level was treated with DBSINT® and the other level received cortical-cancellous bone autograft. At the end of the experimental time, all the animals were euthanized. The spine segments were analyzed macroscopically, radiographically, microtomographically, histologically and histomorphometrically. The SINT-Life® Putty shows a perfect osteointegration in all the histological specimens. A high percentage of newly formed bone tissue is detected, with lots of trabeculae having structure and morphology similar to the pre-existing bone. In all the specimens collected from DBSINT®-treated animals the presence of hydroxyapatite alone is reported but not the demineralized bone matrix. The presence of newly formed bone tissue can be detected in all the specimens but newly formed bone shows very thin and irregular trabeculae next to the cartilage zone, while away from the border of ossification there are thicker trabeculae similar to the pre-existing bone. The use of the experimental biomaterial SINT-Life® Putty in an ovine model of spine fusion leads to the development of newly formed bone tissue without qualitative and quantitative differences with the one formed with autologous bone. The experimental material DBSINT® seems to lead to less deposition of newly formed bone with wider intertrabecular spaces. Following these results, we planned and submitted to the Ethical Committee a clinical study to evaluate the safety and efficacy of SINT-Life® product in comparison to autologous bone, as an alternative treatment for spine fusion procedures

Introduction. Purpose: Injuries to the long bones of the upper limb resulting in bone defects are rare but potentially devastating. Literature on the management of these injuries is limited to case reports and small case series. The aim of this study was to collate the most recent published work on the management of upper limb bone defects to assist with evidence based management when confronted with these cases. Materials and Methods. Methods: Following a preliminary search that confirmed the paucity of literature and lack of comparative trials, a scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) was conducted. A literature search of major electronic databases was conducted to identify journal articles relating to the management of upper limb long bone defects published between 2010 and 2020. Results. Results: A total of 46 publications reporting on the management of 341 patients were reviewed. Structural autograft, bone transport, one-bone forearm and the induced membrane technique were employed in an almost equal number of cases. The implemented strategies showed similar outcomes but different indications and complication profiles were observed. Conclusions. Conclusion: Contemporary techniques for the management of post-traumatic upper limb bone defects all produce good results. Specific advantages, disadvantages and complications for each modality should be considered when deciding on which management strategy to employ for each specific patient, anatomical location, and defect size

Background. Synthetic interbody spinal fusion devices are used to restore and maintain disc height and ensure proper vertebral alignment. These devices are often filled with autograft bone to facilitate bone bridging through the device while providing mechanical stability. Nonporous polyetheretherketone (PEEK) devices are widely used clinically for such procedures. 1. Trabecular Metal devices are an alternative, fabricated from porous tantalum. It was hypothesized that the porous Trabecular Metal device would better maintain autograft viability through the center of the device, the ‘graft hole’ (GH). Methods. Twenty-five goats underwent anterior cervical discectomy and fusion using a Trabecular Metal or PEEK device for 6, 12 or 26 weeks. The GH of each device was filled with autograft bone morsels harvested from the animal at implantation. Fluorochrome labeling oxytetracycline was administered to the animals and used to determine bone viability in the device regions. Following necropsy, the vertebral segments were embedded in poly(methyl methacrylate) sectioned and analyzed using fluorescence and backscatter electron (BSE) imaging. The percent of bone tissue present within the GH was measured as a volume percent using BSE images (Fig. 1). Results. Bone percent analysis demonstrated that there was no significant difference (p<0.05) in volume of bone tissue within the GH of the two devices at 6 and 26 weeks (Fig. 2). At 12 weeks the animals implanted with the Trabecular Metal device had significantly greater volumes of bone within the GH region. Viable bone was observed in the host bone region and periprosthetic to the implant of all PEEK (n=12) and Trabecular Metal (n=12) animals within the study, determined by the presence of fluorescent labels (Fig. 3). Viable bone was also observed in the GH region of all animals with a Trabecular Metal device. However, only 5 of 12 PEEK animals showed bone viability within the GH (2 at 12 weeks and 3 at 26 weeks). A Fisher's exact comparison of the number of animals with viable bone in the GH showed a significant difference between the two devices, p<0.05. Conclusion. Autograft viability was better maintained within the GH for the porous Trabecular Metal device compared to the PEEK device. Although the amount of bone tissue within the GH of the PEEK devices was determined to have no significant difference compared to the Trabecular Metal devices at 6 and 26 weeks, the GH bone tissue was not viable in a number of the PEEK animals at each time point. The interconnected network and high volume porosity of the Trabecular Metal device may have allowed for fluid exchange, angiogenesis and increased blood supply to the autograft morsels. The viability of the autograft morsels also played an important role in the success of bone bridging through the GH between the vertebral endplates. In this animal model it was demonstrated that the autograft bone placed within the PEEK spinal fusion device did not always remain viable after implantation, but sometimes only filled the GH and did not necessarily facilitate fusion between the vertebrae as intended

Joint surface restoration of deep osteochondral defects represents a significant unmet clinical need. Moreover, untreated lesions lead to a high rate of osteoarthritis. The current strategies to repair deep osteochondral defects such as osteochondral grafting or sandwich strategies combining bone autografts with ACI/MACI fail to generate long-lasting osteochondral interfaces. Herein, we investigated the capacity of juvenile Osteochondral Grafts (OCGs) to repair osteochondral defects in skeletally mature animals. With this regenerative model in view, we set up a new biological, bilayered, and scaffold-free Tissue Engineered (TE) construct for the repair of the osteochondral unit of the knee. Skeletally immature (5 weeks old) and mature (11 weeks old) Lewis rats were used. Cylindrical OCGs were excised from the intercondylar groove of the knee of skeletally immature rats and transplanted into osteochondral defects created in skeletally mature rats. To create bilayered TE constructs, micromasses of human periosteum-derived progenitor cells (hPDCs) and human articular chondrocytes (hACs) were produced in vitro using chemically defined medium formulations. These constructs were subsequently implanted orthotopically in vivo in nude rats. At 4 and 16 weeks after surgery, the knees were collected and processed for subsequent 3D imaging analysis and histological evaluation. Micro-computed tomography (µCT), H&E and Safranin O staining were used to evaluate the degree of tissue repair. Our results showed that the osteochondral unit of the knee in 5 weeks old rats exhibit an immature phenotype, displaying active subchondral bone formation through endochondral ossification, the absence of a tidemark, and articular chondrocytes oriented parallel to the articular surface. When transplanted into skeletally mature animals, the immature OCGs resumed their maturation process, i.e., formed new subchondral bone, partially established the tidemark, and maintained their Safranin O-positive hyaline cartilage at 16 weeks after transplantation. The bilayered TE constructs (hPDCs + hACs) could partially recapitulate the cascade of events as seen with the immature OCGs, i.e., the regeneration of the subchondral bone and the formation of the typical joint surface architecture, ranging from non-mineralized hyaline cartilage in the superficial layers to a progressively mineralized matrix at the interface with a new subchondral bone plate. Cell-based TE constructs displaying a hierarchically organized structure comprising of different tissue forming units seem an attractive new strategy to treat osteochondral defects of the knee

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

Autologous bone has been the gold standard for grafting material in foot and ankle arthrodesis. While autograft use has been effective, the harvest procedure does present risks to the patient including readmission, infection, and persistent graft harvest site pain. Previous studies have examined graft harvest site pain, but most have focused on the iliac crest and none have long term follow-up. The purpose of this study was to examine long-term (7–10 year) harvest site pain in subjects undergoing autograft harvest from multiple sites for hindfoot and/or ankle arthrodesis. Sixty (60) subjects underwent hindfoot or ankle arthrodesis supplemented with autograft as part of the control arm of a prospective, randomized trial. The mean subject age was 59.4 years (range, 24.7–76.8) and mean body mass index was 30.6 kg/m2 (range, 22.0–44.0). There were 29 males and 31 female subjects. Subjects had the tibiotalar (37.9%), subtalar (24.1%), talonavicular (10.3%), subtalar/talonavicular (5.1%), or subtalar/calcaneocuboid/talonavicular (22.4%) joints arthrodesed. Autograft was harvested from either the proximal tibia (51.7%), iliac crest (17.2%), calcaneous (15.5%), distal tibia (6.8%), or other location (8.6%). Graft harvest site pain was evaluated using a 100-point visual analog score (VAS), with clinically significant pain being any score greater than 20. Subjects were followed a mean of 9.0 years (range, 7.8–10.5). The percentage of subjects who reported clinically significant pain was 35.7%, 21.4%, 18.2%, 10.5%, 8.9%, and 5.2% at 2, 6, 12, 24, 52 weeks, and final follow-up (7.8–10.5 years), respectively. The mean VAS autograft harvest site pain at final follow-up was 4.4 (range, 0.0–97.0), with 37.9% of subjects reporting at least some pain. For three subjects (5%) with clinically significant pain (VAS >20) at final follow-up, two had proximal tibial harvest sites and one had an iliac crest harvest site. There was no correlation between graft volume and harvest site pain. This study is the first to examine long-term pain following autologous bone graft harvest for hindfoot and/or ankle arthrodesis. Over a third of patients reported having some pain at an average follow-up of nine years, with 5% experiencing clinically significant pain. The results of this study suggest that harvesting autograft bone carries a risk of persistent, long-term pain regardless of the volume of graft that is harvested. This potential for persistent pain should be considered when informing patients of procedure risks and when deciding to use autograft or a bone graft substitute material

Aims: Clinical use of BMP-7: actual situation The tibial pseudoarthrosis. The Friedlander paper can be considered the only golden standard about the clinical application. It is a prospective, randomized clinical trial comparing BMP-7 with fresh bone autograft. The results of the BMP-7 are similar under to use of fresh bone autograft. Some cases of very serious pseudoar-throsis treated with BMP-7 have demonstrated an high percentual of clinical recovery. In UOA of traumatology and in I Orthopaedic Clinic of Turin University the pseudoarthrosis are treated with the Ilizarov’s technique, not with the autologous transplantation, so Friedlander’s results are not discriminant for the our work. Methods: In our department the guide lines for BMP-7 application are:. Delayed union of the docking point in pseudoarthrosis of long bones treated with the Ilizarov technique (resection and distractional osteogenesis) and traditional techniques (decortication and fresh bone autograft) not suitable for application. The treatment of a pseudoartrhosis is based on our classification in type: I, II, III, IV (septic). Traditional techniques failure. Choice first treatment in very difficult cases of limb reconstruction and bone nonunion. Results: From 30/09/2002 till 28/02/2007 55 patients have been treated with BMP-7. In 5 cases it has been associated with autologus bone graft. The material is: 24 cases of traditional techniques failure, 17 cases in wich traditional techniques were unfeasible to be treated and 9 docking point nonunions, in 5 particular cases. Mean age is 38 years. Before last intervention, mean number of porevious operation is 6,5 with mean time before BMP procedures is 3 years. 43 patients healed, 9 are under treatment and 3 are failure. The mean time of healing was 4 months. Conclusions: The series is strictly observational but results are effective in front of the complexity of cases. Late complications suggest that BMP-7 induces bone formation but mechanical function could need time to be achived.According to literature the BMP-7 should be usefull also in more simple cases but more prospective clinical double blind randomised series and cost decreasing are necessary to extend the indications for BMP-7 application

In the treatment of bone non-unions an alternative to bone autografts is the use of bone morphogenetic proteins (BMP-2, BMP-7) with powerful osteoinductive and osteogenic properties. In clinical settings, BMPs are applied using absorbable collagen sponges. Supraphysiological doses are needed and major side effects may occur as induce ectopic bone formation, chronic inflammation and excessive bone resorption. In order to increase the efficiency of the delivered for BMPs we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic, ANI) or trabecular bone (random distributed porosity, isotropic, ISO). We hypothesize that anisotropic structure would enhance osteoconductive properties of the scaffolds increasing rhBMP-2 regenerative properties. In vitro, both scaffolds presented similar mechanical properties, rhBMP-2 retention and delivery capacity. For in vivo testing, a rat femoral critical size defect model was created. Four groups were assessed depending on the implant applied to the bone defect: ISO, unloaded isotropic sponge; ISO-BMP, isotropic sponge loaded with 5 μg of hrBMP-2; ANI, unloaded anisotropic sponge; and ANI-BMP, anisotropic sponge loaded with 5 μg of hrBMP-2. Regeneration was allowed for 10 weeks. X-ray, μCT, biomechanical testing and histology were used to evaluate repair. Independently of their structure, sponges loaded with rhBMP-2 demonstrate increased bone volume, and biomechanical properties than their controls (p<0.01 and p<0.05 respectively). Globally, ANI-BMP group demonstrated better bone regeneration outputs with increased defect bridging (p<0.05 when compared ANI-BMP vs ISO-BMP groups). In conclusion, anisotropic cryostructured collagen scaffolds improve the efficiency of rhBMP-2 in bone regeneration

Background. We have reported an injectable L-pNIPAM-co-DMAc hydrogel with hydroxyaptite nanoparticles (HAPna) which promotes mesenchymal stem cell (MSC) differentiation to bone cells without the need for growth factors. This hydrogel could potentially be used as an osteogenic and osteoconductive bone filler of spinal cages to improve vertebral body fusion. Here we investigated the biocompatibility and efficacy of the hydrogel in vivo using a proof of concept femur defect model. Methods. Rat sub-cut analysis was performed to investigate safety in vivo. A rat femur defect model was performed to evaluate efficacy. Four groups were investigated: sham operated controls; acellular L-pNIPAM-co-DMAc hydrogel; acellular L-pNIPAM-co-DMAc hydrogel with HAPna; L-pNIPAM-co-DMAc hydrogel with rat MSCs and HAPna. Following 4 weeks, defect site and organs were histologically examined to determine integration, repair and inflammatory response, as well as Micro-CT to assess mineralisation. Results. No inflammatory reactions or toxicity were seen in any animal. Enhanced bone healing was observed in aged exbreeder female rats where hydrogel was injected with increased deposition of collagen type I. Integration of the hydrogel with surrounding bone was observed without the need for delivered MSCs; native cell infiltration was also seen and bone formation was observed within all hydrogel systems investigated. Conclusion. This novel hydrogel is biocompatible, facilitates migration of cells, promotes increased bone formation and integrates with surrounding bone. This system could be injected to fill spaces within and surrounding spinal cages to aid in cage fixation and spinal fusion without the need for harvesting of bone autografts, thus reducing operative risk and surgical cost. Conflicts of Interest: None. Source of Funding: BMRC, MERI Sheffield Hallam University

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.

Introduction. Augmentation of spinal fusion using bone grafts is largely mediated by the osteoinductive potential of mesenchymal stem cells (MSC) that reside in cancellous bone. Iliac crest (IC) is a common autograft, but its use presents an increased risk for donor-site pain, morbidity and infection. Degenerative facet joints (FJ) harvested during facetectomy might servce as alternative local grafts. In this study, we conducted an intra-individual comparison of the osteogenic potential of MSC from both sources. Methods. IC and degenerative FJ were harvested from 8 consecutive patients undergoing transforaminal lumbar interbody fusion surgery for spinal stenosis. MSC were isolated by collagenase digestion, selected by plastic adherence and minimally expanded for downstream assays. Clonogenic and osteogenic potential was evaluated by colony formation assays in control and osteogenic culture medium. Osteogenic properties, including alkaline phosphatase (ALP) induction, matrix mineralization and type I collagen mRNA and protein expression were characterized using quantitative histochemical staining and reverse transcription PCR. Spontaneous adipogenesis was analysed by adipocyte enumeration and gene expression analysis of adipogenic markers. Results. Average colony-forming efficiency in osteogenic medium was equal between IC (38±12%) and FJ (36±11%). Osteogenic potential at the clonal level was 55±26 and 68±17% for IC and FJ MSC, respectively. Clonogenic and osteogenic potential were significantly negatively associated with donor age. Osteogenic differentiation led to significant induction of ALP activity in IC (6-fold) and FJ (8-fold) MSC. Matrix mineralization quantified by Alizarin red staining was increased by osteogenic differentiation, yet similar between both MSC sources. Protein expression of type I collagen was enhanced during osteogenesis and significantly greater in IC MSC. Correspondingly, COL1A2 mRNA expression was higher in osteogenically differentiated MSC from IC. Adipocyte numbers showed significant differences between IC (63±60) and FJ (18±15) MSC under osteogenic conditions. Negative (GREM1) and positive (FABP4) adipogenic markers were not differentially expressed between sources. Conclusion. MSC from IC and degenerative FJ largely display similar clonogenic and osteogenic properties in vitro. Differences at the molecular level are not likely to impair the osteoinductive capacity of FJ MSC. Facetectomy samples are viable bone autografts for intervertebral spinal fusion

Introduction. Acetabular fractures management is controversial since, despite a good anatomical reduction, clinical outcome is not satisfactory very often and the probability of a total hip arthroplasty (THA) is high. Surgical treatment include long operating times, large approach, blood loss, neural and muscle damage, and a high risk of failure and secondary osteoarthritis related to bone necrosis, cartilage damage, and bone loss. We hypothesized that the acetabular fracture management affected the clinical and radiological outcome of THA after posttraumatic arthritis. Materials and Methods. We compared 49 patients (49 hips) initially treated conservatively followed some months later by THA in conjunction with acetabular reconstruction (group 1); and 29 patients (29 hips) who had undergone THA after a failed osteosynthesis (group 2). There were more associated fractures according to Letournel in group 2. The mean age was 59.3±15.8 years for group 1 and 52.9±15.2 years for group 2. The mean delay between fracture and THA was 75.4±5 months for group 1 and 59.4±5 for group 2. The mean follow-up was 11.7 in group 1 and 10.2 in group 2. Preoperative bone defect was similar. We used bone autograft in 13 hips (26.5%) in group 1 and four (13.6%) in group 2. We used acetabular reconstruction plates in 2 hips with a pelvic discontinuity in group 1. Complications, clinical outcome according to Harris Hip Score, and radiological reconstruction were compared. Two-way ANOVA with repeated measures were used for comparison. Results. There were 5 cups revised for aseptic loosening in group 1 and 2 in group 2. The cumulative probability of not having a cup revision at 16 years was 90.6% (95% confidence interval (CI) 78,1 to 100) for group 1 and 94.1% (95% CI 86.5 to 100) for group 2 (p=0.76). There were 4 sciatic palsies in group 2, 4 of which developed after trauma and 2 after osteosynthesis. There were no infections. Although pre-operative clinical score was better in group 1, post-operatively at latest follow-up there were no differences. The radiological reconstruction was better in group 1 for version angle (p=0.03) and abductor lever arm (p=0.02). The change from the pre- to post-operative situation was greater in group 2 for the latter (Delta value, p=0.002). The rate of post-operative heterotopic ossifications was greater in group 2 (p=0.04). Conclusions. Long-term clinical and radiograph results are good in patients who underwent THA after a complex acetabular fracture, however, primary THA in conjunction with acetabular reconstruction had a lower number of complications and a better radiographic acetabular reconstruction than a THA after failed osteosynthesis

Introduction. Elevated remodelling of subchondral bone and marrow tissues has been firmly established as diagnostic and prognostic radiological imaging marker for human osteoarthritis. While these tissues are considered as promising targets for disease-modifying OA drugs, the development of novel treatment approaches is complicated by the lack of knowledge whether similar tissue changes occur in rodent OA models and poor understanding of joint-specific molecular and cellular pathomechanisms in human OA. Here, we describe the establishment of a human OA explant model to address this crucial niche in translational preclinical OA research. Methods. Osteochondral (knee, spine) and bone (iliac crest) clinical specimens were acquired from patients undergoing total knee arthroplasty (n=4) or lumbar spine fusion using bone autografts (n=6). Fresh specimens were immediately cut in equal-sized samples (50–500 mg wet weight) and cultured in 8 mL osteogenic medium for one week. Samples were either left untreated (control) or stimulated with lipopolysaccharide (LPS, 100 ng/mL) in the absence and presence of transforming growth factor-beta inhibitor (SB-505124, 10 μm). Pro-collagen-I (Col-I), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) secretion was determined in conditioned medium by ELISA. Tissue viability was assessed using MTT and alkaline phosphatase (ALP) activity staining. Results. Explanted tissues remained viable after one week culture in control and treatment conditions. Osteocytes, subchondral marrow spaces and calcified cartilage stained positive for ALP activity without gross morphological differences between groups. Median basal secretion levels were Col-I (2.3 ng/mg), IL-6 (90 pg/mg) and MCP-1 (25 pg/mg). LPS treatment led to a significant increase of IL-6 (330 pg/mg) and MCP-1 (70 pg/mg), but not Col-I secretion. Interestingly, inhibition of TGF-beta signalling in osteochondral tissues specifically reduced Col-I levels (0.4 ng/mg) compared to controls and LPS-treated samples. LPS-induced IL-6 and MCP-1 levels were slightly reduced (−120 pg/mg, p=0.03) and increased (+50 pg/mg) by SB-505124 treatment, respectively. IL-6 and MCP-1 levels were strongly correlated under basal (r=0.80) and treatment conditions (r=0.62). Conclusion. In this study, we provided proof of concept for the first ex vivo explant model of human osteoarthritis. Osteochondral tissue specimens can readily be cultured without loss of tissue viability and mount a robust inflammatory response upon LPS challenge. Treatment with a potential disease-modifying agent (TGF-beta signalling inhibitor) reduced collagen metabolism in bone and marrow and modified cytokine and chemokine expression. The osteochondral explant model might be highly valuable to evaluate disease-modifying OA drugs

Introduction. Implantation of total hip replacement (THR) remains a concern in patients with developmental dysplasia of the hip (DDH) because of bone deformities and previous surgeries. In this frequently young population, anatomical reconstruction of the hip rotation centre is particularly challenging in severe, low and high dislocation, DDH. The basic principles of the technique and the implant selection may affect the long-term results. The aim of the study was to compare surgical difficulties and outcome in patients who underwent THR due to arthritis secondary to moderate or severe DDH. Material and Methods. We assessed 131 hips in patients with moderate DDH (group 1) and 56 with severe DDH (Group 2) who underwent an alumina-on-alumina THR between 1999 and 2012. The mean follow-up was 11.3 years (range, 5 to 18). Mean age was 51.4 years in group 1 and 42.2 in group 2. There were previous surgery in 5 hips in group 1 and in 20 in group 2 (p<0.001). A dysplastic acetabular shape type C according to Dorr and a radiological cylindrical femur were both more frequent in group 2 (in both cases p<0.001). We always tried to place the acetabular component in the true acetabulum. Smaller cups (p<0.001), screw use for primary fixation (p<0.001) and bone autograft used as segmental reinforcement in cases of roof deficiency (p<0.001) were more frequent in group 2. Radiological analysis of the cup included acetabular abduction, version and Wiberg angles, horizontal, vertical, and hip rotation centre distances, and acetabular head index. Abductor mechanism reconstruction according to the lever arm distance and height of the greater trochanter was also evaluated. Cup placement within or outside Lewinnek´s safe zone was recorded. Two-way ANOVA with repeated measures were used to analyse clinical and radiological changes. Results. There were 6 cups revised for aseptic loosening, three in each group. Survivorship analysis at 15 years: 97.3% (95% IC 94.4–100) for group 1 and 93.0% (95% IC 85.2–100) for group 2 (p=0.186). Despite a worse preoperative status in group 2, the outcome improved similarly in both groups. Postoperative radiological measurements were better in group 1 except for acetabular acetabular and version angles. The improvement from the pre- to the post-operative situation was greater in group 2 except for the height of the greater trochanter. Acetabular component placement within the Lewinnek´s safe zone was similar in both groups. All revised cups were outside this zone. No osteolysis or complications related to the use of ceramics were found. Conclusions. The alumina-on-alumina THR provided good results in both groups including pain relief and functional improvement. Placing the acetabular component in the true acetabulum inside the Lewinnek safe zone can ensure a good result in these challenging dysplastic hips

INTRODUCTION. In the treatment of nonunions, and other complications of bone repair, an attractive alternative to bone autografts would be the use of a combination of autologous mesenchymal progenitors cells (MSCs), biomaterials and growth factors. Our goal was to determine the therapeutic potential and contribution to the repair process of different sources of mesenchymal stem cells for the treatment of nonunions. METHODS. The right femur of Sprague-Dawley (SD) rats was stabilized with an aluminum plate (20 mm long, 4 mm wide, 2 mm thick) and four screws (1.5 mm diameter, 8 mm long). A diaphyseal critical size defect was performed (5 mm). Six groups (n=6–8 animals each) were created. A nonunion group (Control group, empty defect); LBA group, live bone allograft; BMP2 group, rhBMP-2 (2 μg) in collagen sponge; PCL group, polycaprolactone scaffold; PMSCs group, PCL scaffold loaded with 5×10. 6. periosteum-derived MSCs; and BMSCs group, PCL scaffold loaded with 5×10. 6. bone marrow-derived MSCs. For cell tracking purposes, LBA and MSCs were derived from SD-GFP transgenic rats. The repair process was followed up by x-rays up to sacrifice, week 10. After sacrifice, femurs were analyzed by micro computed tomography (μCT), histology and immunohistochemistry. For multiple comparisons one-way ANOVA followed by Dunnett”s test for single comparisons was used. Statistical significance was established for p<0.05. RESULTS. Control group did not show healing during follow up or by μCT and histological analysis. Treatment groups BLA and BMP2 showed full healing by week 10 (LBA, 6 out of 6 animals; BMP2, 4 out of 6 animals). The repair callus was quantified by mCT, Control group showed limited formation of bone (11.47±2.01 mm. 3. ) while both LBA and BMP2 groups showed increased bone formation by week 10 when compared with control group (LBA, 35.36±2.24 mm. 3. , p=0.0022; BMP2, 33.32±1.84 mm. 3. , p=0.0022). Histological and μCT analysis confirmed the experimental nonunion model. In PCL treated groups a low number of animals showed radiographic healing: PCL group 1 out of 8 animals; PMSCs group, 2 out of 6 animals; BMSCs group, 0 out of 6 animals. Interestingly, quantification of the repaired callus showed that only PMSCs group produced a significant volume of bone when compared with the Control group (PMSCs, 24.97±6.03 mm. 3. , p=0.0411). PCL and BMSCs groups do not produced significant amount of bone in the repair callus (PCL, 19.00±4.25 mm. 3. , p=0.3095; BMSCs, 12.88±2.38 mm. 3. , p=0.9372). Healing was confirmed by histology and μCT analysis. Finally, the engraftment of transplanted cells was analysed by immunohistochemistry (anti-GFP antibody). Of the three groups receiving cells only the LBA group showed positive signal for GFP at week 10-post surgery. CONCLUSIONS. In conclusion, periosteum-derived progenitor cells are suitable for mimetic autograft design although integration is not yet achieved

Aims

The aim of this study is to report the implant survival and factors associated with revision of total elbow arthroplasty (TEA) using data from the Dutch national registry.