功能仿生性多孔钛合金支架材料防治早期股骨头坏死的效应及机制研究

Osteonecrosis of the femoral head is a common and refractory disease induced by many factors, such as glucocorticoid and alcohol. Core decompression combined with bone graft implantation in the early stage is the main treatment method to prevent necrosis from femoral head collapse. Because of the complex pathological processes including blood supply failure, insufficient repair and weight bearing collapse, the bone graft with single function could not meet the diverse needs for the treatment, leading to a treatment failure. Regarding to this clinical problem and in view of our study on the multiple biological effects of magnesium, a bionic porous titanium scaffold will be designed to provide appropriate mechanical support to the femoral head. By tackling the technical difficulties of multi-arc ion plating, magnesium coating will be prepared onto the porous titanium scaffolds. The effects and mechanisms between degradation of the coating and phase composition, such as grain size and coating thickness, will be clarified. Then, through cultivation of osteoblast, osteoclast and vascular endothelial cell in vitro, implantation into rabbit model with osteonecrosis of the femoral head, the effect of bone healing and angiogenesis of the scaffolds will be observed and the related mechanisms will be revealed. By using sheep femoral head necrosis model simulating the force condition in big animal, the possibility of functional scaffolds to prevent the collapse of the osteonecrosis of the femoral head will be systematically evaluated. This study would provide a novel biomaterial and a new treatment method to the treatment of osteonecrosis of the femoral head.

股骨头坏死是由激素、酒精等多种因素诱发的骨科常见难治性疾病，早期通过髓芯减压结合骨移植物填充阻止坏死向塌陷发展是其主要治疗手段。由于该病血供破坏、修复障碍和负重塌陷的复杂病理过程，现有单一功能骨移植物难以满足整体治疗需求，常导致治疗失败。针对上述临床难题，基于项目组前期镁金属多重生物学效应的研究基础，本项目拟通过多孔钛合金支架的仿生设计，实现股骨头坏死区的有效力学支撑；通过攻克多弧离子镀膜关键技术，完成多孔钛合金支架内外表面镁涂层制备，阐明晶粒尺寸、物相组成、涂层厚度等结构组态对涂层降解的影响规律；通过成骨、破骨和血管内皮细胞培养，兔激素性股骨头坏死模型植入，揭示复合支架材料在股骨头坏死治疗中促进新骨形成与血管诱导的生物学效应与机制；通过羊股骨头坏死模型植入，模拟大动物受力情况，系统观察功能仿生多孔钛合金镁涂层支架材料对股骨头坏死塌陷的综合防治作用，为该病的临床治疗提供新材料与新方法。

本课题以股骨头坏死早期外科治疗缺乏有效的生物材料进行结构支撑的问题为切入点，围绕镁涂层修饰多孔钛合金股骨头支撑棒的研发，设计如下几个方面的研究：1）通过攻克多弧离子镀膜关键技术，完成多孔钛合金支架内外表面镁涂层制备，体内外研究证实生物活性镁涂层修饰的多孔 Ti6Al4V 支架材料在各时间点的骨长入量显著增加，周围组织的血管化增强，表现出更好的成骨和成血管活性；2）通过不同浓度镁离子环境的体外细胞学研究，初步探索和验证了镁离子通过促进PDGF-BB表达从而促进骨生成和血管生成的机制，并明确了镁离子促进HUVEC增殖和血管生成的最适浓度，对镁离子在临床上骨植入物治疗骨缺损中的应用提供了理论依据和指导；3）3D打印多孔PEEK支架制备及镁涂层修饰的生物学效应评价研究，证实镁离子能够增强多孔PEEK支架内部的骨长入和骨整合，其机制可能与促进有利于成骨的H型血管形成相关；4）顺利完成多孔钛合金股骨头支撑棒的设计、制备，确定各项设计参数。通过液氮冷冻法成功制备羊股骨头坏死模型，并通过影像学、组织学验证了模型的有效性，为后续的研究奠定了基础。由于疫情原因，股骨头支撑棒的动物体内植入尚未实施，将在后续研究中补充。目前，相关研究成果已发表SCI 收录论文9篇，授权国家发明专利1项，实用新型专利1项，参加国内外会议交流4次，培养博士研究生2名和硕士研究生1名，达到预期指标。