Construction Of Biofunctional Titanium-based Interface And Its Application For Bone Fracture Repair Under Osteoporotic Conditions

Titanium and titanium alloy was widely used as the bone repair implants and dental implants due to its good mechanical properties and biocompatibility.However,in practical application,its surface biological inert makes it lack of the potential of osteoinduction,hindering its bone integration with surrounding bone tissues as well as leading to implant loosening and implanting.Moreover,the early loosening and movement of titanium based material under osteoporosis are more likely to occur.Therefore,how to effectively modify the surface of titanium materials to improve the bone integration and the success rate of implant has been a hot research topic of titanium substrates surface modifying.Based on that,we constructed functional multilayer structure with the effect of inhibiting osteoclasts and promote the osteogenesis on the titanium alloy substrates via layer-by-layer assembly(LBL)techniques to promote the repairing of osteoporotic fracture.The main research contents are as follows:1.The remodeling of osteoporotic fracture by biomimic multilayered structures on Ti6Al4 V implants interface.We constructed the functional multilayer structure consist of chitosan/gelatin multilayers containing bone morphogenetic protein 2(BMP2)and an antiosteoporotic agent of calcitonin(CT)on the Ti6Al4V(TC4)implants through layer-by-layer(LBL)electrostatic assembly technique.The results dispalyed that,the obtained titanium alloy implant(TC4/LBL/CT/BMP2)can regulate the release of loaded calcitonin and BMP2 agents in a sustaining manner to accelerate the bone formation and simultaneously inhibit bone resorption.In vitro results showed that the MSCs cells on TC4/LBL/CT/BMP2 present the high level of alkaline phosphatase(ALP)activity,osteocalcin production,mineralization capacity and osteoblast-related gene expression among all groups,respectively.Besides,in vivo studies of micro-CT analysis,routine histological and immunohistochemical analysis also collectively demonstrate that the TC4/LBL/CT/BMP2 implant can dramatically promote the formation and remodeling of new bone in osteoporotic rabbits after implantation for 30 days and 90 days,respectively.In vivo push-out testing further confirms that the TC4/LBL/CT/BMP2 implant has the highest interfacial shear strength and favorable bone-implant osseointegration.Overall,the research exhibits a good application prospect for promoting bone remodeling and bone healing in patients with osteoporosis.2.The osteoporotic fracture repairing by functional molecular reservoir multilayers on the titanium interface.The chitosan grafted by beta cyclodextrin(?-CD)used as a molecular reservior(Chi-CD)to loading the calcitriol(1,25(OH)2D3,VD3)which is the active metabolite of Vitamin D.Thus we obtain the functional molecular reservior(Chi-CD@VD3).Then it was assemblyed to Ti6Al7 Nb surface with calcitonin(CT)through layer-by-layer(LBL)electrostatic assembly technique to construct the funtional multilayers(Ti6Al7Nb/LBL/ Chi-CD@VD3/CT).In vitro results show that the osteoblasts on Ti6Al7Nb/ Gel/ChiCD@VD3/Gel/CT present the high level of alkaline phosphatase(ALP)activity,mineralization capacity and osteoblast-related gene expression and protein expression among all groups,respectively.Moreover,Ti6Al7Nb/LBL/Chi-CD@VD3/CT can promote the expression of calcium binding protein via VD3 molecular to promote the transport and storage of calcium,thus to strengthen mineralization process.In vivo evaluation indicated that Ti6Al7Nb/LBL/Chi-CD@VD3/CT has the highest material and bone interface bonding strength,showing a potential to promote bone formation and bone integration.