Study On Construction Of Surface Heterojunction On Titanium Implants And Its Performance Of Promoting Osteogenesis

With the aging of the modern population and the frequent occurrence of traffic accidents,diseases such as large segmental bone defects and artificial joint replacements have increased dramatically,and there is an urgent need to develop artificial implant materials with efficient osseointegration capabilities.Titanium-based implants can improve the efficiency of bone regeneration at the implant interface,however,bone tissue is in a complex physiological microenvironment,and bone is mainly composed of collagen fibers with piezoelectric response and micro-nano structure.The integration can be achieved by applying electrical stimulation through exogenous electric fields.However,there are few studies that simultaneously simulate bone mechanics and electrophysiological microenvironment to regulate osteogenic differentiation.A large amount of research work is currently focused on the natural composition of the bone itself and the micro and nano topology of the implant surface bionic constructs to improve osteogenic efficacy,but there are still problems such as slow osteogenic rate.Titaniumbased implants have good mechanical properties and excellent biocompatibility,and have a wide range of clinical applications and high market demand.Therefore,this study was conducted to simulate the complex environment of bone tissue by constructing force-electric microenvironment on the surface of titanium-based implants simultaneously,which can be used to improve the osseointegration effect of titanium-based implants,promote bone tissue regeneration,and provide ideas and approaches for the preparation of new implant materials,which has important scientific research value and clinical significance.In this study,the construction of titanium dioxide/bismuth trioxide heterojunction on the surface of titaniumbased implants was carried out as follows.(1)Based on the semiconductor properties of titanium dioxide,titanium dioxide nanocones were constructed in situ on the medical titanium surface,while bismuth trioxide was compounded on the active sites of titanium dioxide nanocones by hydrothermal reaction to form titanium dioxide/bismuth trioxide heterojunctions with bone-like elastic modulus and built-in electric field.Transmission electron microscopy and X-ray photoelectron spectroscopy results showed that the titanium dioxide/dibismuth trioxide heterojunctions were successfully constructed on the titanium surface.The results of nanoindentation and scanning Kelvin probe force microscopy demonstrated that the titanium dioxide/bismuth trioxide heterojunction on titanium surface has bone-like elastic modulus(7～10 GPa).Further,the results of Mott Schottky test confirmed that the titanium dioxide/bismuth trioxide heterojunction formed an internal electric field,and COMSOL theoretical simulations further confirmed the existence of the internal electric field,which could realize the coupling of force-electric microenvironment on the titanium surface.In vitro cellular experiments demonstrated that the titanium-based implant could promote the proliferation of rat bone marrow mesenchymal stem cells with good biocompatibility.It provides a biological basis for the subsequent osteogenic differentiation experiments.(2)The controlled construction of the titanium surface bone-mimicking microenvironment is expected to improve bone regeneration efficiency.Based on the above research work,this study was conducted to explore the regulation of osteogenic behavior by simulating the mechanic-electric microenvironment in bone in vivo and in vitro experiments.In vitro cellular experiments showed that the construction of titanium dioxide/bismuth trioxide heterojunctions on the titanium surface significantly promoted the adhesion and spreading of bone marrow mesenchymal stem cells,increased alkaline phosphatase activity on the implant surface cells,and showed significant calcium nodule deposition,as well as upregulated the expression of ALP,OCN,RUNx2 and BMP-2 related osteogenic genes,which was 2～3 times higher than that of the pure titanium group and 1 ～ 2 fold.Further,the successful activation of force-associated protein YAP pathway and electrical-related signaling pathway PI3 K indicated that osteogenic differentiation of bone marrow BMSCs was influenced by both force and electrical signaling.In vivo implantation experiments in animals also showed that this functionalized titanium-based implant could exponentially increase the osseointegration ability at the implant interface,and the expression of osteogenic-related genes such as ALP was significantly up-regulated to about that of the pure titanium group,while the bone volume fraction was 1.88 times higher than that of the pure titanium group and 1.38 times higher than that of the titanium dioxide group.This study successfully constructed force-electric microenvironment on the surface of titaniumbased implants for promoting rapid bone regeneration,which is a guideline for the design and precise regulation of bone implant biomaterials.