硬组织植入羟基磷灰石基抗菌涂层的制备及其生物学效应研究

Postoperative infection and limited operating life are the current serious problems in the clinic application of Hard tissue implants. It has attracted extensive critical attention to create new hard tissue implant biomaterials with more safety and longer service life in the field of biomedical implant materials. Hydroxyapatite-coated implants, as the widely used promising substitute materials for hard tissue replacement,will be systematically studied in the present research. The project will study and create new hydroxyapatite-coated implants with antibacterial property, bioactivity and long servicing life by plasma spraying and biochemical process. (1) The plasma spray process will be studied to prepare bone-mimicking hydroxyapatite coatings, which is modified with ions doping method by mimicking bone composition to improve their bone regeneration, antibacterial and permanence properties. (2)Antibiotics and antibacterial agents will be loaded in the hydroxyapatite coatings to improve their antibacterial property. The project will study the technology to prepare hydroxyapatite coatings that resemble human bone in composition and structure, study the strategies to load antibacterial agents and the controlled release mechanisms of agents in the coatings and the antibacterial mechanism. (3)The effects of coatings、biological factors and antibacterial agents on bone cells and bone tissues and their synergy effects will be studied. The project will also clarify in vitro and in vivo the mineralization mechanism of the coatings, cytotoxicity and biocompatibility evaluation, hemolysis test, accumulation and elimination in and out of organs and other biological effects. One or two kinds of promsing implants will be developed based on antibacterial hydroxyapatite coatings, providing the scientific foundation and key techniques for the clinical applications.

针对硬组织植入体材料临床应用的突出问题，即植入体引起术后感染和使用寿命问题，研究具有高度安全性、生物活性和长使用寿命的新型硬组织植入体材料是医用植入材料的研究重点。本项目拟以广泛临床应用的羟基磷灰石基涂层材料为研究对象，探索抗菌涂层构建及其生物学效应作用机制等关键科学问题，利用等离子喷涂并结合生物化学方法，制备具有抗菌性、生物活性和长使用寿命的羟基磷灰石基涂层材料。（1）研究仿骨组分羟基磷灰石涂层的等离子喷涂方法，通过离子掺杂改性制备仿骨羟基磷灰石涂层以提高其成骨性、稳定性和抑菌性。（2）研究羟基磷灰石涂层抗菌组元的负载、控释与抗菌机制，通过负载抗菌组分实现植入体的抗菌性。（3）研究羟基磷灰石抗菌涂层的生物学效应，探索材料、生物因子和抗菌组分对骨组织的影响及协同效应，阐明抗菌涂层的矿化机制、细胞毒性、溶血性、体内积累和排出机制。为羟基磷灰石抗菌涂层材料的临床应用奠定科学基础并提供关键技术。

针对硬组织植入体感染和生物相容性问题，本项目以广泛临床应用的羟基磷灰石基涂层材料为研究对象，探索了抗菌涂层构建及其生物学效应作用机制并研制了多种具有高度安全性、抗菌性和生物活性的新型硬组织植入材料。为羟基磷灰石抗菌涂层材料的临床应用奠定科学基础并提供关键技术。.（1）从结构角度开展了羟基磷灰石的仿生合成和生物矿化机制研究，制备了具有等级有序结构的羟基磷灰石，探索了反应过程中的固态拓扑相变机制，建立了构筑羟基磷灰石有序结构的新方法，为羟基磷灰石生物材料的仿生结构合成提供了新的研究视角和思路。.（2）从成分角度开展了对多元素掺杂羟基磷灰石的制备研究，构建了一种制备多元素掺杂羟基磷灰石材料的新方法，制备了一元、二元、三元以及多元仿骨掺杂羟基磷灰石等多种材料。研究了其掺杂机制、晶体结构以及生物学效应，从晶体学、计算化学角度揭示了不同元素改性仿生羟基磷灰石结构与生物学效应之间的构效关系。.（3）选择具有广谱杀菌效果的Ag为抗菌元素，制备了一系列不同浓度超微量银掺杂的羟基磷灰石纳米粉体、固相烧结体相材料、等离子喷涂涂层材料以及复合涂层材料，详细研究了其抗菌组元释放、抗菌性、细胞毒性以及体内外骨诱导性，对其抗菌机制给出了科学解释。.（4）构建了具有pH响应性的装载抗肿瘤药物/包覆壳聚糖的多孔羟基磷灰石微球药物释放体系。该材料作为药物可控释放和蛋白运输载体、骨填充材料在肿瘤的治疗和术后修复中具有潜应用前景。.（5）通过优化粉体造粒和喷涂工艺，利用真空等离子喷涂工艺研制了多种羟基磷灰石基抗菌涂层植入体，涂层各项性能指标均优于现行医用植入体的规定标准。所制备的微量银掺杂羟基磷灰石抗菌涂层和多元素微量掺杂仿骨组分羟基磷灰石抗菌涂层具备抗菌性、相容性和成骨性，有望实现产业化并应用于临床。