Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial

Background: ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis. Methods: Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5–10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority. Findings: With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging). Interpretation: Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic. Funding: EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/FP7-HEALTH-2009); REBORNE Project (GA: 241876

Résultats à long terme d'une tige fémorale anatomique totalement recouverte d'hydroxyapatite dans les reprises de prothèses totales de hanche

TOURS-BU Médecine (372612103) / SudocSudocFranceF

Simultaneous Evaluation of Bone Cut and Implant Placement Accuracy in Robotic-Assisted Total Knee Arthroplasty

Background: This study aimed to evaluate the accuracy of bone cuts and implant placements, simultaneously, for total knee arthroplasty (TKA) performed using a system with an active robotic arm. Methods: Two experienced orthopaedic surgeons performed TKA on ten cadaveric legs. Computed tomography scans were performed to compare the bone cuts and implant placements with the preoperative planning. The differences between the planned and actual bone cuts and implant placements were assessed using positional and angular errors in the three anatomical planes. Additionally, the cut–implant deviations were calculated. Statistical analysis was performed to detect systematic errors in the bone cuts and implant placements and to quantify the correlations between these errors. Results: The root-mean-square (RMS) errors of the bone cuts (with respect to the planning) were between 0.7–1.5 mm and 0.6–1.7°. The RMS implant placement errors (with respect to the planning) varied between 0.6–1.6 mm and 0.4–1.5°, except for the femur and tibia in the sagittal plane (2.9°). Systematic errors in the bone cuts and implant placements were observed, respectively, in three and two degrees of freedom. For cut–implant deviations, the RMS values ranged between 0.3–2.0 mm and 0.6–1.9°. The bone cut and implant placement errors were significantly correlated in eight degrees-of-freedom (ρ ≥ 0.67, p Conclusions: With most of the errors below 2 mm or 2°, this study supported the value of active robotic TKA in achieving accurate bone cuts and implant placements. The findings also highlighted the need for both accurate bone cuts and proper implantation technique to achieve accurate implant placements

Comparative bone tissue integration of nanostructured and microroughened dental implants

International audienceAIM:The aim was to compare osteointegration of nanostructured implants to a microsurface widely used for titanium dental implants.MATERIALS & METHODS:Commercial titanium dental implants with smooth or microroughened surfaces were nanostructured. Implants were inserted into the femoral condyles of rabbits. After 2 and 4 weeks, histomorphometry calculation was performed.RESULTS:Nanotubes measuring 60 nm in diameter were observed on both S-NANO (roughness: 0.05 μm) and R-NANO (roughness: 0.40 μm) surfaces. The MICRO surface exhibited typical random cavities (roughness: 2.09 μm). At 4 weeks, bone-to-implant contact values were significantly higher for the R-NANO than for the MICRO surface while no differences were observed at 2 weeks.CONCLUSION:Overall, this study shows that the nanostructured surfaces improved osteointegration similar or higher than the MICRO

Bone regeneration strategies with bone marrow stromal cells in orthopaedic surgery

International audienceBone is the most transplanted tissue human with 1 million procedures every year in Europe. Surgical interventions for bone repair are required for varied reasons such as trauma resulting non-union fractures, or diseases including osteoporosis or osteonecrosis. Autologous bone grafting is the gold standard in bone regeneration but it requires a second surgery with associated pain and complications, and is also limited by harvested bone quantity. Synthetic bone substitutes lack the osteoinductive properties to heal large bone defects. Cell therapies based on bone marrow or ex vivo expanded mesenchymal stromal stem cells (MSCs) in association with synthetic calcium phosphate (CaP) bone substitutes may be alternatives to autologous bone grafting. This manuscript reviews the different conventional biological and synthetic bone grafting procedures as well as the more recently introduced cell therapy approaches used in orthopaedic surgery for bone regeneration. Some clinical studies have demonstrated safety and efficacy of these approaches but regeneration of large bone defects remain challenging due to the absence of rapid and adequate vascularisation. Future directions in the field of bone regeneration are presented, such as testing alternative cell sources or in situ fabrication of vascularized bone grafts in patients