Results in patients undergoing total hip arthroplasty (THA) for femoral head osteonecrosis (ON) when compared with primary osteoarthritis (OA) are controversial. Different factors like age, THA type or surgical technique may affect outcome. We hypothesized that patients with ON had an increased revision rate compared with OA. We analysed clinical outcome, estimated the survival rate for revision surgery, and their possible risk factors, in two groups of patients. In this retrospective cohort analysis of our prospective database, we assessed 2464 primary THAs implanted between 1989 and 2017. Patients with OA were included in group 1, 2090 hips; and patients with ON in group 2, 374 hips. In group 2 there were more men (p<0.001), patients younger than 60 years old (p<0.001) and with greater physical activity (p<0.001). Patients with lumbar OA (p<0.001) and a radiological acetabular shape type B according to Dorr (p<0.001) were more frequent in group 1. Clinical outcome was assessed according to the Harris Hip Score and radiological analysis included postoperative acetabular and femoral component position and hip reconstruction. Kaplan-Meier survivorship analysis was used to estimate the cumulative probability of not having revision surgery for different reasons. Univariate and multivariate Cox regression models were used to assess risk factors for revision surgery. Clinical improvement was better in the ON at all intervals. There were 90 hips revised, 68 due to loosening or wear, 52 (2.5%) in group 1, and 16 (4.3%) in group 2. Overall, the survival rate for revision surgery for any cause at 22 years was 88.0 % (95% CI, 82-94) in group 1 and 84.1% (95% CI, 69 – 99) in group 2 (p=0.019). Multivariate regression analysis showed that hips with conventional polyethylene (PE), compared with highly-cross linked PEs or ceramic-on-ceramic bearings, (p=0.01, Hazard Ratio (HR): 2.12, 95% CI 1.15-3.92), and cups outside the Lewinnek´s safe zone had a higher risk for revision surgery (p<0.001, HR: 2.57, 95% CI 1.69-3.91). Modern highly-cross linked PEs and ceramic-on-ceramic bearings use, and a proper surgical technique improved revision rate in patients undergoing THA due to ON compared with OA

Introduction. Vascularized fibular grafting following tumor resection is an essential treatment option in limb salvage surgery. This study aimed to assess the surgical and oncological outcomes of patients treated in Denmark between 2010 and 2022. Method. We present a retrospective review of a national cohort comprising 27 patients. The indications were 13 cases of Ewing sarcoma, 12 cases of osteosarcoma, and 2 cases of giant cell tumor. The median age at surgery was 16 years (range: 2-39), and the median follow-up was 82 months (range: 12-138). Patients were analyzed overall and stratified into upper and lower extremity groups based on tumor location. Result. The primary rate of graft union was 63%, and after secondary procedures, the overall rate of graft union was 67%, with a median time to union of 13 months (range: 7-29). The reoperation rate was 74%, while the rate of limb salvage was 93%, with two patients undergoing amputation during follow-up. The 5-year overall survival rate was 81% (95% CI: 61-92). Patients with upper extremity tumors were more likely to attain graft union (92% vs. 47%, p=0.02) and less likely to undergo multiple reoperations (17% vs 60%, p=0.047) compared to patients with lower extremity tumors. Conclusion. Vascularized fibula grafting remains a valuable option in limb salvage surgery with acceptable long-term outcomes. However, especially in lower extremity cases, a low rate of graft union and multiple reoperations are to be expected

Osteosarcoma is a highly malignant primary tumor of bone tissue. The 5-year survival rate of patients with metastasis is below 20% and this scenario is unchanged in the last two decades, despite great efforts in pre-clinical and clinical research. Traditional preclinical models of osteosarcoma do not consider the whole complexity of its microenvironment, leading to poor correlation between in vitro/in vivo results and clinical outcomes. Spheroids are a promising in vitro model to mimic osteosarcoma and perform drug-screening tests, as they (i) reproduce the microarchitecture of the tumor, (ii) are characterized by hypoxic regions and necrotic core as the in vivo tumor, (iii) and recapitulate the chemo-resistance phenomena. However, to date, the spheroid model is scarcely used in osteosarcoma research. Our aim is to develop a customized culture dish to grow and characterize spheroids and to perform advanced drug-screening tests. The resulting platform must be adapted to automated image acquisition systems, to overcome the drawbacks of commercial spheroids platforms. To this purpose, we designed and developed a micro-patterned culture dish by casting agarose on a 3D printed mold from a CAD design. We successfully obtained viable and reproducible homotypic osteosarcoma spheroids, with two different cells lines from osteosarcoma (i.e., 143b and MG-63). Using the platform, we performed viability assays and live fluorescent stainings (e.g., Calcein AM) with low reagent consumption. Moreover, the culture dish was validated as drug screening platform, administrating Doxorubicin at different doses, and evaluating its effect on OS spheroids, in terms of morphology and viability. This platform can be considered an attractive alternative to the highly expensive commercial spheroid platforms to obtain homogeneous and reproducible spheroids in a high-throughput and cost effective mode

Previous scientific studies have highlighted how coupling is an important element affecting total hip arthroplasty's survival. This study aims to evaluate whether metal-on-metal (MOM) coupling could be a statistically significant risk factor. The data from the regional joint registry (Registro dell'Impiantologia Protesica Ortopedica, RIPO) was used for analysis. The data collection accuracy of this registry was 97.2% in 2017. We retrospective evaluate all MOM total hip arthroplasties (THAs) implanted in our department between January 01st 2000 and December 31st 2011. We used a control group composed by all other prosthesis implanted in our Department in the same time lapse. We registered 660 MOM THAs. Mean age of patients was 66.9 years. 603 patients have a >36mm head, while 78 a <36 mm one. Neck modularity was present in half of patients. 676 implants were cementless. We registered 69 revisions, especially due to aseptic mobilization (16 THAs), implant breakage (9 THAs) and periprosthetic fracture (6 THAs). The MOM THAs overall Kaplan-Meier survival rate was 87.2 at 15 years, and the difference between MOM THAs and other implants two curves is statistically significant (p<0.05). Male sex is a significant risk factors. Further evaluations are in progress to establish the presence of any additional risk factors. We think weight and/or BMI may be included in this category. Our study confirms the data currently present in the literature regarding a lower survival of metal-on-metal hip prostheses. The male sex is a statistically significant risk factor (p<0.05), while age, head size and modularity of the prosthetic neck are not statistically significant (p>0.05). Any new finds will be presented at the congress venue

Introduction and Objective. The surgical strategy for acetabular component revision is determined by available host bone stock. Acetabular bone deficiencies vary from cavitary or segmental defects to complete discontinuity. For segmental acetabular defects with more than 50% of the graft supporting the cup it is recommended the application of reinforcement ring or ilioischial antiprotrusio devices. Acetabular reconstruction with the use of the antiprotrusion cage (APC) and allografts represents a reliable procedure to manage severe periprosthetic deficiencies with highly successful long-term outcomes in revision arthroplasty. Objective. We present our experience, results, critical issues and technical innovations aimed at improving survival rates of antiprotrusio cages. Materials and Methods. From 2004 to 2019 we performed 69 revisions of the acetabulum using defrosted morcellized bone graft and the Burch Schneider anti-protrusion cage. The approach was direct lateral in 25 cases, direct anterior in 44. Patients were re-evaluated with standard radiography and clinical examination. Results. Eight patients died from causes not related to surgery, and two patients were not available for follow up. Five patients were reviewed for, respectively, non-osseointegration of the ring, post-traumatic loosening with rupture of the screws preceded by the appearance of supero-medial radiolucency, post-traumatic rupture of the distal flange, post-traumatic rupture of the cemented polyethylene-ceramic insert, and dislocation treated with new dual-mobility insert. Among these cases, the first three did not show macroscopic signs of osseointegration of the ring, and the only areas of stability were represented by the bone-cement contact at the holes in the ring. Although radiographic studies have shown fast remodeling of the bone graft and the implant survival range from 70% to 100% in the 10-year follow up, the actual osseointegration of the ring has yet to be clarified. To improve osseointegration of the currently available APC whose metal surface in contact with the bone is sandblasted, we combined the main features of the APC design long validated by surgical experience with the 3D-Metal Technology for high porosity of the external surface already applied to and validated with the press fit cups. The new APC design is produced with the 3D-Metal technology using Titanium alloy (Ti6Al4V ELI) that Improves fatigue resistance, primary stability and favorable environment for bone graft ingrowth. We preview the results of the first cases with short-term follow up. Conclusions. Acetabular reconstruction with impacted morcellized bone graft and APC is a current and reliable surgical technique that allows the restoration of bone loss with a high survival rate of the implant in the medium to long term. The new 3D Metal Cage is designed to offer high friction for the initial stability. The high porosity of the 3D Metal structure creates a favorable environment for bone growth, thus providing valid secondary fixation reproducing the results achieved with the 3D metal press fit cup

Intervertebral disc degeneration (IDD) affects more than 80% of the population all over the world. Current strategies for the treatment of IDD are based on conservative or surgical procedures with the aim of relieving pain. Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy in recent decades, but studies showed that the particularly hostile microenvironment in the intervertebral disc (IVD) can compromise cells survival rate. The use of exosomes, extracellular vesicles released by various cell types, possess considerable economic advantages including low immunogenicity and toxicity. Exosomes allow intercellular communication by conveying functional proteins, RNA, miRNA and lipids between cells. The purpose of this study is to assess the therapeutic effects of exosomes derived from Wharton Jelly mesenchymal stromal cells (WJ-MSC) on human nucleuspulposus cells (hNPC) in an in vitro 3D culture model. Exosomes (exos) were isolated by tangential flow filtration of WJ-MSC conditioned media and characterized by: quantification with BCA test; morphological observation with TEM, surface marker expression by WB and size evaluation by NTA. Confocal microscopy has been used to identify exosomes marked with PKH26 and monitor fusion and/or incorporation in hNPC. hNPC were isolated from waste surgical material from patients undergoing discectomy (n = 5), expanded, encapsulated in alginate beads and treated with: culture medium (control group); WJ-MSC exos (WJ-exos) at different concentrations (10 μg/ml, 50 μg/ml and 100 μg/ml). They were then analysed for: cell proliferation (Trypan Blu); viability (Live/Dead Assay); quantification of nitrites (Griess) and glycosaminoglycans, GAG (DMBB). The hNPC in alginate beads treated for 7 days were included in paraffin and histologically analysed to determine the presence of extracellular matrix (ECM) components. Finally, the expression levels of catabolic and anabolic genes were evaluated through real-time polymerase chain reaction (qPCR). All concentrations of WJ-exos under exam were capable to induce a significant increase in cell proliferation after 10 and 14 days of treatment (p < 0.01 and p < 0.001, respectively). Live/Dead assay showed a decrease in cell death at 50 μg/ml of WJ-exos (p < 0.05). While cellular oxidative stress indicator, nitrite production, was reduced in a dose-dependent way and statistically significant only with 100 μg/ml of WJ-exos (p < 0.05). WJ-exos at 10 and 100 μg/ml induced a significant increase in GAG content (p < 0.05; p < 0.01, respectively) confirmed by Alcian Blu staining. Exos derived from WJ-MSC modulated gene expression levels by increasing expression of ACAN and SOX-9 genes and reducing significantly of IL-6, MMP-1, MMP-13 and ADAMTS-5 levels (p < 0.05; p < 0.01) compared to the control group. Our results supported the potential use of exosomes from WJ-MSC for the treatment of IDD. Exosomes improved hNPC growth, attenuated ECM degradation and reduced oxidative stress and inflammation. This study offers a new scenario in IVD regeneration, promoting the potential use of extracellular vesicles as an alternative strategy to cell therapy

Introduction and Objective. TKA have shown both excellent long-term survival rate and symptoms and knee function improvement. Despite the good results, the literature reports dissatisfaction rates around 20%. This rate of dissatisfaction could be due to the overstuff that mechanically aligned prostheses could produce during the range of motion. Either size discrepancy between bone resection and prosthetic component and constitutional mechanical tibiofemoral alignment (MTFA) alteration might increase soft tissue tension within the joint, inducing pain and functional limitation. Materials and Methods. Total knee arthroplasties performed between July 2019 and September 2020 were examined and then divided into two groups based on the presence (Group A) or absence (Group B) of patellofemoral overstuff, defined as a thickness difference of more than 2 mm between chosen component and bone resection performed, taking into account at least one of the following: femoral medial and lateral condyle, medial or lateral trochlea and patella. Based on pre and post-operative MTFA measurements, Group A was further divided into two subgroups whether the considered alignment was modified or not. Patients were assessed pre-operatively and at 6 months post-op using the Knee Society Score (KSS), Oxford Knee Score (OKS), Forgotten Joint Score (FJS), Visual Analogue Scale (VAS) and Range of Motion (ROM). Results. One hundred total knee arthroplasties were included in the present study, 69 in Group A and 31 in group B. Mean age and BMI of patients was respectively 71 and 29.2. The greatest percentage of Patellofemoral Overstuff was found at the distal lateral femoral condyle. OKS, KSS functional score, and FJS were statistically significant higher in patients without Patellofemoral Overstuff. Therefore, Group A patients with a non-modified MTFA demonstrated statistically significant better KSS, ROM and FJS. Conclusions. Patellofemoral Overstuff decrease post-operative clinical scores in patients treated with TKA. The conventional mechanically aligned positioning of TKA components might be the primary cause of prosthetic overstuffing leading to worsened clinical results. Level of evidence: III; Prospective Cohort Observational study;

Introduction and Objective. Despite pure alumina have shown excellent long-term results in patients undergoing total hip arthroplasty (THA), alumina matrix composites (AMCs) composed of alumina and zirconium oxide are more commonly used. There are no comparative studies between these two different ceramics. We performed a retrospective case-control study to compare results and associated complications between AMC from two manufacturers and those with pure alumina from another manufacturer. Materials and Methods. 480 uncemented THAs with ceramic on ceramic (CoC) bearing surfaces (288 men and 192 women; mean age of 54.1 ± 12.4 years), were implanted from 2010 to 2015. Group 1: 281 THAs with pure alumina; Group 2A: 142 with AMC bearing in a trabecular titanium cup. Group 2B: 57 hips with AMC bearing with a porous-coated cup. Results. The mean follow-up was 7.3 years. There was one late infection in group 1, eight dislocations, three in group 1 (1.1%), three in group 2A (2.1%), all with a 36 mm femoral head, and two in group 2C (3.5%). Liner malseating was found in one hip in group 1, and in five hips in group 2C, of these, there were four liner fractures (7.0%). Four cups were revised for iliopsoas impingement (three in group 1 and one in group 2B). Two cups were revised for aseptic loosening, one in group 1 and one in group 2A, and four revised femoral stems in group 2A, three for subsidence and another for postoperative periprosthetic B. 2. fracture. The mean preoperative Harris Hip Score was 48.6 ± 3.3 in the whole series and 93.9 ± 7.2 at the end of follow-up. The survival rate of revision for any cause was 98.2% (95% Confidence Interval: 96.6–99.8) at ten years for group 1, 95.8% (95% CI: 92.1–99.5) for group 2A, and 91.1% (95% CI: 83.7–98.5) for group 2B (log-rank 0.030). Conclusions. Outcome of uncemented CoC THA in young patients was satisfactory at mid-term in all three groups. However, liner fractures were frequent in group 2B. All dislocated hips in group 2A had a 36 mm femoral head diameter, and revision due to any cause was less frequent in group 1. Pure alumina CoC THA can be used as a benchmark for comparison with newer CoC THAs

Introduction and Objective. Osteoarthritis (OA) is the most common inflammatory and degenerative joint disease. Mesenchymal Stromal Cells (MSCs), with their chondro-protective and immune-regulatory properties, have been considered as a new approach to treat OA. Considering the risk of cell leakage outside the articular space and the poor survival rate after intra-articular (IA) injection, we hypothesized that cell encapsulation in cytoprotective hydrogels could overcome these limitations and provide cells with a suitable 3D microenvironment supporting their biological activity. We previously generated micromolded alginate particles (diameter 150 μm) and demonstrated the long-term viability of microencapsulated MSCs isolated from human adipose tissue (hASCs). Encapsulated cells maintained their in vitro ability to sense and respond to a pro-inflammatory environment (IFN-γ/TNF-α or synovial fluids from OA patients) by secreting PGE. 2. , IDO, HGF and TGF-β. In this study, we evaluated the anti-OA efficacy of these microencapsulated hASCs in a post-traumatic OA model in rabbits. Materials and Methods. OA was surgically induced by anterior cruciate ligament transection (ACLT)-mediated destabilization of the right knee in rabbits (n=24). Eight weeks after surgery, destabilized joints were injected (IA, 26G needle) with 200 μL of either PBS, blank microparticles, non-encapsulated or microencapsulated cells (5×10. 5. cells). Six weeks after injection, rabbits were euthanized and all destabilized (right) and sham-operated (left contralateral) joints were dissected and analyzed for OA severity. Tibial subchondral bone histomorphometric parameters were measured by quantitative micro-computed tomography (micro-CT). Histological sections of samples were analyzed after Safranin-O staining and quantitatively assessed according to a modified Osteoarthritis Research Society International (OARSI) scoring system. Immunohistochemical detection of NITEGE was performed to assess the extracellular matrix degradation. Results. Micro-CT analysis of destabilized joints confirmed that the rabbit ACLT significantly affected the tibial subchondral bone architecture as early as eight weeks, as revealed by significant changes of the subchondral bone parameters of operated joints compared to the sham operated joints. In particular, destabilized joints exhibited a Bone Volume/Tissue Volume ratio (BV/TV) ranging from 53.4% to 56.6%, compared to a mean BV/TV of 65.4% for sham operated joints. All destabilized joints also exhibited a significantly increased modified OARSI score, ranging from 7.4±0.4 for those injected with encapsulated cells to 8.9±0.2 for those injected with PBS, as compared to 4.8±0.4 for sham-operated joints. Of interest, we identified a slight, while not significant, reduction of the severity of OA lesions after injection of microencapsulated cells using the modified OARSI scoring. Finally, semi-quantitative analysis of NITEGE immunostaining revealed a significant increase in all destabilized joints that were injected with PBS or blank microparticles, in comparison with sham ones. On the contrary, NITEGE immunostaining in destabilized joints that were injected with non-encapsulated or encapsulated hASC revealed a significant reduced NITEGE immunostaining, indicating a decreased matrix degradation. Conclusions. Our data suggest that the microencapsulated hASCs exerted their anti-OA properties after IA injection in rabbit knees, as evidenced by the tendency toward a reduced modified OARSI score, and most importantly a significant reduction in NITEGE immunostaining associated matrix degradation. Further studies are now warranted to investigate the anti-OA efficacy of microencapsulated hASCs in the long-term

Introduction and Objective. Total joint replacement (TJR) is indicated for patients with end-stage osteoarthritis (OA) where conservative treatment has failed. Approximately 1.3 million primary hip replacement surgeries have been recorded in the United Kingdom since 2003 and this number is set to rise due to an increase in obesity as well as an ageing population. Total hip replacement (THR) has a survival rate of 85% at 20 years; the most common reason for failure is aseptic loosening which often occurs secondary to osteolysis caused by immune-mediated inflammation responses to wear debris generated from the materials used in the THR implant. Therefore, by understanding the biological steps by which biomaterials cause immune-mediated reactions it should be possible to prevent them in the future thereby reducing the number of costly revision surgeries required. Materials and Methods. The human osteoblast-like cell line (MG-63) was seeded at a density of 100,000 cell per well of a 6-well plate and treated with and increasing doses (0.5, 5, and 50mm. 3. per cell) of cobalt-chromium (CoCr) particles generated on a six-station pin-on-plate wear generator or commercially available ceramic oxide nanopowders (Al. 2. O. 3. and ZrO. 2. ) for 24 hours. TNF-alpha was used as a positive control and untreated cells as a negative control. Cells were then analysed by transmission electron microscopy (TEM) to determine whether the osteoblasts were capable of phagocytosing these biomaterials. MG-63 cells were used in conjunction with trypan blue and the XTT Cell Proliferation II Kit to assess cytotoxicity of the biomaterials investigated. Cells supernatants were also collected and analysed by enzyme-linked immunosorbant assay (ELISA) to investigate changes in pro-inflammatory protein secretion. Protein extracted from lysed cells was used for western blotting analysis to investigate RANKL protein expression to determine changes to osteolytic activation. Lysed cells were also used for RNA extraction and subsequent cDNA synthesis for real-time quantitative polymerase chain reaction (RT-qPCR) in order to assess changes to pro-inflammatory gene expression. Results. There was no significant change to cellular viability or proliferation in the osteoblasts treated with CoCr, Al. 2. O. 3. or ZrO. 2. when compared to the untreated negative control. TEM images showed clear and distinct intracellular vesicles within the cell cytoplasm which contained CoCr, Al. 2. O. 3. and ZrO. 2. RANKL expression increased at 5 and 50mm. 3. per cell CoCr and 50mm. 3. per cell Al. 2. O. 3. and ZrO. 2. Pro-inflammatory protein secretion of CXCL10, IL-8, and IL-6 all significantly increased at 50mm. 3. per cell CoCr, Al. 2. O. 3. , and ZrO. 2. Similarly to the protein secretion, CXCL10, IL-8, and IL-6 gene expression was significantly upregulated at 50mm. 3. per cell CoCr, Al. 2. O. 3. , and ZrO. 2. Conclusions. Increased in vitro RANKL expression in response to CoCr, Al. 2. O. 3. , and ZrO. 2. may result in disruption of bone metabolism and lead to osteolysis which can contribute to aseptic loosening in vivo. Significant increases in IL-6 are particularly important because as well as being a pro-inflammatory cytokine, IL-6 is also secreted by osteoblasts in order to stimulate mature osteoclast formation to mediate bone breakdown. CXCL10 and IL-8 are chemotactic cytokines and increased secretion in response to implant biomaterials can contribute to ongoing pro-inflammatory responses through the recruitment of monocytes and neutrophils respectively. This is interesting as in vivo data demonstrates increased cellular infiltrate in patients experiencing responses to implant materials. Overall, these findings show clear immune activation as well as altered metabolism of MG-63 osteoblast cells in response to implant wear debris which is in agreement with in vivo clinical reports

Direct metal printed (DMP) porous iron implants possess promising mechanical and corrosion properties for various clinical application. Nevertheless, there is a requirement for better co-relation between in vitro and in vivo corrosion and biocompatibility behaviour of such biomaterials. Our present study evaluates absorption of porous iron implants under both static and dynamic conditions. Furthermore, this study characterizes their cytocompatibility using fibroblastic, osteogenic, endothelial and macrophagic cell types. In vitro degradation was performed statically and dynamically in a custom-built set-up placed under cell culture conditions (37 °C, 5% CO2 and 20% O2) for 28 days. The morphology and composition of the degradation products were analysed by scanning electron microscopy (SEM, JSM-IT100, JEOL). Iron implants before and after immersion were imaged by μCT (Quantum FX, Perkin Elmer, USA). Biocompatibility was also evaluated under static and dynamic in vitro culture conditions using L929, MG-63, HUVEC and RAW 264.7 cell lines. According to ISO 10993, cytocompatibility was evaluated directly using live/dead staining (Live and Dead Cell Assay kit, Abcam) in dual channel fluorescent optical imaging (FOI) and additionally quantified by flow cytometry. Furthermore, cytotoxicity was indirectly quantified using ISO conform extracts in proliferation assays. Strut size of DMP porous iron implants was 420 microns, with a porosity of 64% ± 0.2% as measured by micro-CT. After 28 days of physiological degradation in vitro, dynamically tested samples were covered with brownish degradation products. They revealed a 5.7- fold higher weight loss than statically tested samples, without significant changes in medium pH. Mechanical properties (E = 1600–1800 MPa) of these additively manufactured implants were still within the range of the values reported for trabecular bone, even after 28 days of biodegradation. Less than 25% cytotoxicity at 85% of the investigated time points was measured with L929 cells, while MG-63 and HUVEC cells showed 75% and 60% viability, respectively, after 24 h, with a decreasing trend with longer incubations. Cytotoxicity was analysed by two-way ANOVA and post-hoc Tukey's multiple comparisons test. Under dynamic culture conditions, live-dead staining and flow cytometric quantification showed a 2.8-fold and 5.7-fold increase in L929 and MG-63 cell survival rates, respectively, as compared to static conditions. Therefore, rationally designed and properly coated iron-based implants hold potential as a new generation of absorbable Orthopaedic implants

Numerous implanted hip and knee joint arthroplasties have to be replaced due to early or late loosening of the implant, a failure of osteointegration with fibrous tissue at the bone-implant-interface. This could be counteracted by ensuring that cells which attach to the implant surface differentiate towards bone cells afterwards. For this reason, human mesenchymal stem cells (hMSCs) will be included in this study. These cells are naturally available at the bone-implant-interface, multipotent and therefore ideal to study the osteoinductivity of a material. The goal of this pilot study was to test the cell response towards three different titanium grades with a novel surface structuring, as a first step towards achieving an improved implant surface for enhanced osteointegration. Disk-shaped titanium scaffolds with a diameter of 12 mm and a height of 1.2 mm were used. The surface topography (500 µm × 500 µm × 300 µm pores) was generated via laser treatment of the surface. By using nanosecond pulsed laser technique, a rough surface with micro- and nanostructural (titanium droplets) features was automatically formed. Three different batches made of commercially pure titanium grades 1 and 2 (Ti1/Ti2) or Ti6Al4V alloy grade 5 (Ti5) were produced. Four cell types were analysed on these batches: primary hMSCs from one donor (m, 25 y), periosteum derived cells (PDCs), human osteoblasts (hOBs) and periodontal ligament cells (PDLs). Cells were seeded on Ti1, Ti2 and Ti5 scaffolds in triplicates. Resazurin assay to examine cell viability was conducted with all cell types. Measurements were executed on several days after seeding, from day one up to day 14. Actin staining as well as live/dead staining was performed with hMSCs cultured on titanium for 1, 3, 5 or 7 days. The cell viability assay revealed early turning points of growth for osteogenic hOBs (day 3) and PDCs (day 7). HMSCs grew steadily on the material and non-osteogenic PDLs stayed in plateau throughout the cultivation period. With respect to the material, cells demonstrated better proliferation on Ti1 and Ti2 than on Ti5. Live/dead staining showed a high survival rate of hMSCs at each time point and on all three titanium grades, with a neglectable number of dead cells. Actin staining confirmed an enhanced spreading and stretching of hMSCs on Ti1 and Ti2 compared to hMSCs on Ti5. Our pilot data indicates that cells react to different titanium compositions, revealed by increased proliferation on commercially pure titanium (Ti1/2). Furthermore, our results demonstrate that osteogenic cells prefer the novel surface structuring in comparison to non-osteogenic PDL cells, which stayed in plateau. The turning points of growth (hOBs/PDCs) suggest an osteosupportiveness of the surface. Although hMSCs did not show a turning point in growth, their growth was steady and resulted in the highest number of cells along with a well stretched morphology. Due to their good proliferation and response to the material, hMSCs are currently being used for evaluating the osteogenic potential of the novel scaffolds

Purpose. Extraskeletal chondrosarcoma is a rare tumor with an indolent course and high propensity for local recurrence and metastasis. This tumor most commonly presents in the proximal extremities of middle-aged males, and is commonly asymptomatic. Although slow growing, these tumors have a significant risk of eventual relapse and metastases, especially to the lung. There are no clinical trials that investigated the best treatment options for this tumor given its very low incidence. The aim of this study is to present the surgical and clinical results of extraskeletal chondrosarcoma, which is a rare tumor. Methods. In our clinic, the information of 13 patients who were diagnosed with extra-skeletal chondrosarcoma between 2006 and 2018 were retrospectively reviewed. Demographic information, tumor size, surgical treatments, chemotherapy and radiotherapy status, follow-up times, recurrence and metastases of the patients were recorded. Results. This study included 13 patients with an average age of 53.6 ± 15 (range, 28 to 73) years diagnosed with extraskelatal chondrosarcoma. In 8 of the patients, the tumor was located in the lower limbs and it was observed that the thigh was located mostly (46.2%). The mean follow-up period of the patients was 52.8 ± 19.9 (range, 24 to 96) months. All patients underwent extensive resection and only one patient had a positive surgical margin. In the follow-up, 5 (38.5%) of the patients developed recurrence, while 6 patients had lung metastasis (46.2%) and 53.8% (7 patients) of the patients exitus. The mean tumor size was 10.4 ± 3.2 (range, 5 to 17) cm. The median survival time of the patients in the study was 61 (50.5–71.4) months. The 5-year survival rate is 51.8%. There was no significant difference between survival times according to age, gender, side, limb location, postoperative RT, recurrence and presence of lung metastasis (log rank tests p > 0.05). The cut off value for exitus obtained by ROC analysis of tumor size was determined as 11 cm (fig 1). Accordingly, the survival time of patients with 11 cm and above tumor size was observed to be statistically significantly shorter. Conclusion. Consequently, ECM is a rare soft tissue sarcoma with high local recurrence and metastasis capacity. Therefore, close follow-up is recommended. The first option should be extensive resection. Studies with large patient series on the prognostic factors of the future ECM are needed. For any figures or tables, please contact the authors directly

Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Introduction. What is the most effective treatment of the early stages for osteonecrosis of the femoral head? Since the results of several treatment modalities such as multiple drilling, core decompression with or without bone graft, and vascularized fibular grafts have not been completely successful, we tried multiple drilling and stem cell transplantation to treat the early stages of osteonecrosis of the femoral head and to minimize patient morbidity. We report the clinical and radiological results of stem cell transplantation and core decompression. Methods. One hundred and twenty-eight patients (190 hips) who had undergone surgery were divided in two groups based upon which treatment they had received: (1) multiple drilling and stem cell transplantation, and (2) core decompression, curettage, and bone graft. The clinical and radiological results of the two groups were compared. We defined failure as the need for additional surgery, or a Harris hip score of less than 75 points. Results. After a minimum 5-year follow-up in the stem cell transplantation group, 64.3% (27/42) of hips with Stage IIa disease, 56.7% (21/37) of hips with Stage IIb disease, and 46.9% (23/49) of hips with Stage III disease had no additional surgery. In the conventional core decompression group, 66.7% (6/9) of hips with Stage IIa disease, 66.7% (6/9) of hips with Stage IIb disease, and 60% (3/5) of hips with Stage III disease had no additional surgery. Survival rates of patients with Ficat Stages I or II lesions were greater than survival rates for patients with Stage III lesions. There was no difference of survival rate between the two groups. Conclusion. When comparing the clinical and radiological results of the two methods, we found that there was no significant difference between the two groups. The same results were found between stem cell transplantation and the conventional method of core decompression

Although cemented fixation provides excellent results in primary total hip replacement (THR), particularly in patients older than 75 years, uncemented implants are most commonly used nowadays. We compare the rate of complications, clinical and radiological results of three different designs over 75-years-old patients. 433 hips implanted in patients over 75 years old were identified from our Local Joint Registry. Group A consisted of 139 tapered cemented hips, group B of 140 tapered grit-blasted uncemented hips and group C of 154 tapered porous-coated uncemented hips. A 28 mm femoral head size on polyethylene was used in all cases. The mean age was greater in group A and the physical activity level according to Devane was lower in this group (p<0.001 for both variables). Primary osteoarthritis was the most frequent diagnoses in all groups. The radiological acetabular shape was similar according to Dorr, however, an osteopenic-cylindrical femur was most frequently observed in group A (p<0.001). The pre- and post-operative clinical results were evaluated according to the Merle-D'Aubigne and Postel scale. Radiological cup position was assessed, including hip rotation centre distance according to Ranawat and cup anteversion according to Widmer. We also evaluated the lever arm and height of the greater trochanter distances and the stem position. Kaplan-Meier analysis was done for revision for any cause and loosening. The hip rotation centre distance was greater and the height of the greater trochanter was lower in group B (p=0.003, p<0.001, respectively). The lever arm distance was lower in group C (p<0.001). A varus stem position was more frequently observed in group B (p<0.001). There were no intra- or post-operative fractures in group A, although there were five intra-operative fractures in the other groups plus two post-operative fractures in group B and four in group C. The rate of dislocation was similar among groups and was the most frequent cause for revision surgery (8 hips for the whole series). The mean post-operative clinical score improved in all groups. The overall survival rate for revision for any cause at 120 months was 88.4% (95% CI 78.8–98), being 97.8% (95% CI 95.2–100) for group A, 81.8% (95% CI 64.8–98.8) for group B and 95.3% (95% CI 91.1–99.6) for group C (log Rank: 0.416). Five hips were revised for loosening. The overall survival rate for loosening at 120 months was 91.9% (95% CI 81.7–100), being 99.2%(95% CI 97.6–100) for group A, 85.5 (95% CI 69.9 −100) for group B and 100% for group C (Log Rank 0.093). Despite a more osteopenic bone in the cemented group, the rate of peri-prosthetic fractures was higher after uncemented THR in patients older than 75 years. Although the overall outcome is good with both types of fixation, the post-operative reconstruction of the hip, which might be more reliable after cemented fixation, may affect the rate of complications in this population

The aim of this study was to report the procedure survival and patient-reported outcomes in a consecutive series of patients <50yrs at the time of hip arthroplasty with a metal-on-metal hip resurfacing system who have progressed to a minimum of 10yrs follow-up. Patients presenting for treatment of degenerative conditions of the hip electing to undergo hip resurfacing were included in a clinical registry (N=226 patients; 238 procedures). Procedure survival was confirmed by crosschecking to the Australian Orthopaedic Association National Joint Replacement Registry and comparing to all procedures by other surgeons nationwide. Kaplan-meier survival curves with 95% confidence intervals were constructed, while patient-reported outcome measures were compared with t-tests and postoperative scores assessed with anchor analysis to age and gender-matched normative data. At mean follow up of 12 years, six cases were revised with a cumulative survival rate of 96.8% (95%CI 94.2–99.4) at 15 years. Majority of revisions were early (<3yrs) and occurred in females (N=4). Patient-reported general health, disease state, hip function and activity level maintained large improvements beyond 10 years post-implantation and were equal to or exceeded age and gender-matched normative data. Metal-on-metal hip resurfacing in males and females aged <50 years at time of surgery demonstrated a high rate of cumulative survival beyond 10 years follow up. The results demonstrate excellent outcomes in this age group

Total ankle replacement (TAR) is a substitute to ankle fusion, replacing the degenerated joint with a mechanical motion-conserving alternative. Compared with hip and knee replacements, TARs remain to be implanted in much smaller numbers, due to the surgical complexity and low mid-to-long term survival rates. TAR manufacturers have recently explored the use of varying implant sizes to improve TAR performance. This would allow surgeons a wider scope for implanting devices for varying patient demographics. Minimal pre-clinical testing has been demonstrated to date, while existing wear simulation standards lack definition. Clinical failure of TARs and limited research into wear testing defined a need for further investigation into the wear performance of TARs to understand the effects of the kinematics on varying implant sizes. Six medium and six extra small BOX® (MatOrtho) TARs will be tested in a modified knee simulator for 5 million cycles (Mc). The combinations of simulator inputs that mimic natural gait conditions were extracted from ankle kinematic profiles defined in previous literature. The peak axial load will be 3.15 kN, which is equivalent to 4.5 times body weight of a 70kg individual. The flexion profile ranges from 15° plantarflexion to 15° dorsiflexion. Rotation about the tibial component will range from −2.3° of internal rotation to 8° external rotation, while the anterior/posterior displacement will be 7mm anterior to −2mm posterior throughout the gait cycle. The components will be rotated through the simulation stations every Mc to account for inter-station variability. Gravimetric measurements of polyethylene wear will be taken at every Mc stage. A contact profilometer will also be used to measure average surface roughness of each articulating surface pre-and-post simulation. The development of such methods will be crucial in the ongoing improvement of TARs, and in enhancing clinical functionality, through understanding the envelope of TAR performance

Objectives. The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. Methods. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. Results. A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-β1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. Conclusion. Mechanical stress-induced overexpression of TGF-β1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-β1 inhibitor can inhibit articular cartilage degradation. Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1). Bone Joint Res 2018;7:587–594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1