仿骨结构活性增强羟基磷灰石骨修复材料的构建及成骨诱导机制研究

Autologous bone for bone tissue repair in clinical application is available in very limited amounts and often caused morbidity of the donor sites, but allogenous bone and xenogenic bone possess the possibility of initiating an immune response or transmitting diseases. Therefore, Artificial bone repair materials provide an important solution. In this project, the bionic bone structural activity enhanced hydroxyapatite repair materials by functional composite of osteogenic induced biodegradable elements (Mg, Zn) and nano hydroxyapatite (HA) were prepared by spark plasma sintering technology. And then, the influence of material composition, distribution of pore forming agent, behavior of sintering and existence of active elements on the evolution of pore characteristics and mechanical properties of the bone repair materials were investigated. Compared with natural bone, the bionic bone structural repair materials with similar bone structure and mechanical properties would be constructed. Furthermore, behaviors of degradation, ions release, osteogenic induction and bone graft healing of the materials were investigated on the physiological environment. As a result, the interconnection relationship between structural characteristics, active element and mechanical properties, osteogenesis capacity, anti - infection was be obtained. Finally, the cooperative control of materials characteristics and osteogenesis function of the bionic bone structural repair materials can be achieved. Therefore, the problems of artificial bone repair materials such as degradation and osteogenic mismatch, poor bone formation, infection after bone grafting will be improved. The research will develop the basic theory of structural design and controllable preparation of the artificial bone repair materials. At the same time, the research has a promoted role of clinical application of the hydroxyapatite bone repair materials.

目前临床大量需求的自体骨存在来源不足、供骨区并发症而同种异体骨和异种骨存在免疫排斥、疾病传播等问题，应用受到限制，人工骨修复材料提供了重要解决途径。本项目提出将促进成骨诱导的可降解活性元素（Mg、Zn）与纳米羟基磷灰石（HA）进行功能复合、利用放电等离子烧结技术制备仿骨结构活性增强HA骨修复材料的新思路。通过研究材料组成、造孔剂形态分布、烧结行为、活性元素存在形式对孔隙特征演变与力学性能的影响，构建孔隙特性、力学性能与自然骨相似的仿骨结构骨修复材料；进而通过材料在体内降解、离子释放、成骨诱导及植骨愈合行为研究，揭示材料结构特性及活性元素与力学性能、成骨能力、抗感染之间内在关联，实现材料特性与成骨作用协同控制，改善和提高人工骨修复材料存在的降解与成骨不匹配、成骨效果不佳、植骨后感染等问题。相关研究将丰富人工骨修复材料结构设计与可控制备基础理论，对推动HA基骨修复材料临床大量应用具有重要意义。

由于创伤骨折、骨组织坏死、骨肿瘤等导致的骨缺损疾病患者呈快速增长趋势。目前临床大量需求的自体骨存在来源不足、供骨区并发症而同种异体骨和异种骨存在免疫排斥、疾病传播等问题，应用受到限制，人工骨修复材料提供了重要解决途径。本项目将具有促进成骨诱导的可降解活性元素（Mg、Zn）与纳米羟基磷灰石（HA）进行功能复合，利用放电等离子烧结技术制备仿骨结构活性增强HA骨修复材料。通过对复合材料的成分设计及优化、烧结行为、结构特性、力学性能、活性元素作用、生物相容性评价、动物体内成骨行为及其内在关联的研究，获得以下主要研究结果：（1）在烧结温度为950℃时，调控碳酸氢铵（NH4HCO3）造孔剂的加入量可以实现复合材料孔隙特征（孔隙率在40~60%间，孔径尺寸在50～500μm）、力学性能、体外矿化、降解行为及离子释放的控制；（2）复合材料多孔仿骨结构不仅可以为骨髓间充质干细胞的募集、黏附和增殖提供空间，还能利于体液的流动，为细胞的增殖提供养分；（3）复合材料中Zn和Mg活性元素的加入，刺激骨髓间充质干细胞向成骨细胞分化，从而提高了其骨诱导能力；（4）动物体内植入结果表明，多孔仿骨结构与活性元素的共同作用，促进了复合材料的降解与离子释放以及骨髓间充质干细胞的分化，从而提高了其骨修复能力，实现材料结构特性-力学性能-活性元素-成骨作用-植骨愈合协同控制。经上述研究，获得了仿骨结构活性增强羟基磷灰石复合骨修复材料构建与可控制备技术、成骨诱导机制以及材料特性与成骨作用的协同控制机制。在此基础上，开发出具有良好骨修复能力的新型仿骨结构多孔ZnO/HA、MgO/HA和ZnO-MgO/HA复合骨修复材料。所开发的新型仿骨结构复合骨修复材料具有良好的生物相容性和抗菌性能，改善和提高了现有人工羟基磷灰石基骨修复材料的骨修复效果，且具有制备工艺简单和成本低等优势，在临床上具有潜在的应用前景，对人工羟基磷灰石基复合材料在临床上的应用具有推动作用。