Construction Of Bioactive Titanium Implants For Bone Tissue Engineering

Titanium and its alloys have been widely used in bone tissue engineering because of their good biocompatibility and mechanical properties matching with bone tissue,The clinical applications of Ti implants have been limited due to their biological inertness,which is not beneficial for bonding at the bone-implant interface,and results in implant failure.Developing innovative processes to enhance implant bioactivity is a feasible strategy to improve the osseointegration of implants.Furthermore,bone injury repair involves not only the formation of new bone but also other damaged issue surrounding the bone.Peripheral nerves participate in bone development and repair via a host of signals generated through the secretion of neurotransmitters,axon guidance factors.The absence of nerve formation in the new bone tissue can lead to functional deficits,which can result in a poor prognosis.Therefore,bone tissue engineering should consider the repair of multiple sites of bone,including bone and nerves.Based on the above facts,pure titanium is selected as the representative basic material for surface modification to enhance the bioactivity.Surface nanostructure and bioactive ions are introduced to the surface of the implant in order to enhance the osseointegration of implants and promote the regeneration of injured bone tissue.The main findings of this thesis are as follows:(1)Electrochemical insertion of zinc ions into self-organized titanium dioxide nanotube arrays to achieve strong osseointegration with titanium implantsIn this study,inspired by the intercalation mechanism of rechargeable batteries,a feasible electrochemical strategy was developed to insert high-concentration bioactive zinc ions into the lattices of titanium dioxide(TiO2)nanotube arrays with a controlled release performance and without nanostructure collapse.As-prepared TiO2 nanotube had a length of about 1.3 μm and a diameter of about 80 nm.Surface nanostructure and bioactive ions can synergistically enhance the bioactivity of implants.The modified sample is able to undergo long-term zinc ion release and avoid the cytotoxicity caused by the rapid release kinetics of zinc ions.The real-time quantitative polymerase chain reaction(q-PCR)results reveal that the relative expression level of Runx2,osteopontin(OPN),and osteocalcin(OCN),of rBMSCs on zinc ion-inserted TiO2 nanotube array was climbed to 2.95,4.04,and 8.55 folds,respectively,compared to cells on TCPs.The osteogenic related proteins expression was detected by Alkaline phosphatase(ALP)kit,western blot,and immunofluorescence staining,which confirmed the higher expression level of alkaline phosphatase(ALP),OPN,and OCN protein in rBMSCs cultured on inc ion-inserted TiO2 nanotube array.Alizarin red staining results demonstrate that zinc ion-inserted TiO2 nanotube array enhanced the in vitro mineralization of rBMSCs compared to TCPs.The above results demonstrate that zinc ion-inserted TiO2 nanotube array promoted the osteogenic differentiation of rBMSCs.In addition,this electrochemical strategy is able to construct zinc ion-inserted TiO2 nanotube array on three dimensional surfaces.Rat femur defect model confirms that the process-treated implants could significantly improve new bone production around the implants,demonstrating that electrochemical process could significantly improve the osseointegration ability of titanium implants.This versatile electrochemical surface modification process provides a new approach to further improve the bioactivity and osseointegration of titanium implants.(2)Potassium titanate assembled titanium dioxide nanotube arrays endow titanium implants excellent osseointegration performance and nerve formation potentialIn this study,potassium titanate assembled titanium dioxide nanotube arrays were prepared by hydrothermal method.Cell proliferation experiment and live&dead staining show that as-prepared substrates had good biocompatibility,which is adequate for further research.Sustained release of potassium ions can be realized by potassium titanate assembled titanium dioxide nanotube arrays.As-prepared arrays can also promote neural differentiation of neural stem cells while enhancing osteogenic differentiation of mesenchymal stem cells,which is confirmed by q-PCR,Western blot,immunofluorescence staining,and calcium spark imaging.This multifunctional biomaterial is a feasible solution for the repair of bone defects or formation of a fully functional interface between a titanium implant and the surrounding native bone tissue.In summary,the surface nanostructure and bioactive ions is introduced to enhance the bioactivity of titanium implants.The prepared materials are biocompatible and capable of regulating the fate of stem cells.In vivo animal tests verify that the bioactive implants have improved osseointegration capacity and can promote new bone production,which have potential for clinical applications in tissue repair.This thesis provides new approaches to improve the bioactivity and osseointegration capacity,which pave the way for the further clinical application of titanium implants.