The Use Of Filtered Stem Cell Enrichment Technique To Prepare Active Biomaterials For Bone Defect Repair

Background and Objective: Bone defects are incredibly common in clinical practices.Traditional bone grafts such as autologous bone have their own problems.Stem cell enrichment technique intraoperatively acquires sufficient autologous bone marrow mesenchymal stem cells(MSCs)in a non-culture manner and rapidly integrates them with traditional porous bone substitutes,such as beta-tricalcium phosphate(?-TCP),to prepare active biomaterials for bone defect repair.In this study,we use the novel stem cell screen-enrich-combine(-biomaterials)circulating system(SECCS)developed by our department to rapidly prepare MSCs/?-TCP composites,and comprehensively evaluate their safety,feasibility and effectiveness in bone defect repair.Methods: 1: The effect of enrichment on cell safety was evaluated by comparing the biological behavior of MSCs before and after enrichment.2: The biocompatibility of the composites was evaluated by detecting adhesion,spreading,proliferation and differentiation of MSCs in MSCs/?-TCP.3: Bone-fracture patients with bone defects treated with the novel stem cell enrichment technique have been followed up,and both their imaging and functional data were used to evaluate the clinical efficacy of this technique for bone defect repair.4: The feasibility of combining stem cell enrichment with 3D printing in the repair of complex-anatomical bone defects was explored by filling MSCs/?-TCP in a 3D-printed titanium alloy frame matched with lateral femoral epicondyle of the goat.Results:1: The cell morphology,specific surface molecular markers,cell cycle,apoptosis and gene expression profiles of MSCs did not change significantly before and after enrichment,suggesting the safety of enrichment operations.2: In vitro culture,MSCs could effectively adhere,proliferate,spread,secrete matrix in the inner wall of composites and maintain good osteogenic potential.3: Patients with bone defects have achieved good bone defect repair and functional recovery,and the new bone formation rate is significantly better in 1.5 years after surgery than that of purebone-substitutes-implanted patients(91.9±4.8% VS 21.9±12.2%;P<0.01);4: The filled composites significantly enhance the osteointegration of 3D-printed titanium alloy frames.Conclusions: Thus,the filtered stem cell enrichment technique can safely and quickly improve the bone defect repair ability of traditional bone substitutes,and therefore being a promising alternative for autologous bone transplantation.In addition,it is also a new strategy for complex-anatomical bone defects repair to combine this technique with 3D-printing technique.