医用可降解镁合金表面功能化涂层构建及其生物学效应

Based on the fact that chemical composition and structure property of the surface of magnesium (Mg) alloy influence its corrosion resistance and biocompatibility, this project proposes to combine the advantages of plasma electrolytic oxidation (PEO) and hydrothermal techniques to fabricate multifunctional composite coating on the surface of magnesium alloy. After sealing the pores of PEO coating, which possess desirable short-term corrosion resistance, with layer double hydroxide (LDH) coating formed during the hydrothermal process, the corrosion resistance of Mg alloy would be greatly enhanced. The microstructrues and phase transformation mechanisms of the structures will be characterized to reveal their kinetic and thermodynamic behaviors. The fabrication procedures of the structure will be optimized to accurately control the degradation rate of Mg alloy. The adhesion, replication, differentiation of as well as the protein, gene expression behaviors of both bone-related cells and cardiovascular-related cells will be studied at the molecular level to reveal the interaction mechanism between these cells and the fabricated structures. The drug-loading process of LDH coating will be investigated and design platform to intelligently control the release of loaded drug. This project proposed to make use of two different modification methods to control the degradation rate of Mg alloy and regulate cells’ behaviors. The research results obtained in the present project may be used as important reference data in solving fast degradation and unable to regulate cells’ behaviors of biodegradable Mg alloy in clinic application.

本项目基于镁合金表面化学成分及结构特性对其抗腐蚀性及生物相容性的影响，提出利用“等离子体电解氧化”与“水热合成”两种表面改性技术在医用镁合金表面构建多功能复合涂层，利用等离子体电解氧化涂层良好的短期抗腐蚀性及水热层状双金属氢氧化物（LDH）涂层对等离子体电解氧化涂层的封孔作用，协同提高镁合金的抗腐蚀性。探讨镁合金表面多功能复合涂层显微形貌和相结构调控机制，揭示其热力学和动力学行为；优化涂层工艺，实现多功能复合涂层对镁合金降解速率的精确调控。研究成骨和心血管相关细胞在多功能复合涂层表面的粘附、增殖及分化行为，检测相关蛋白、基因的表达规律，阐述多功能复合涂层调控细胞行为的作用机制。探讨LDH涂层的载药方式及设计能够“智能调控”药物释放的开关。本项目提出利用多功能复合涂层调控镁合金的降解速率及材料表面细胞行为，可为解决医用可降解镁合金在临床应用中腐蚀速率快、无法调控细胞行为的问题提供理论依据。

临床跟踪发现，不可降解金属材料存在诸多的问题，如应力屏蔽导致骨萎缩、磨损颗粒导致炎症以及需二次手术取出等。可降解医用镁合金的出现有望解决传统不可降解金属植入体面临的难题。然而，可降解镁合金抗腐蚀性差，另外针对临床植入体的易感染、骨整合不佳、以及肿瘤性骨缺损等问题，本项目主要研究内容包括在镁合金表面基于微弧氧化（Plasma electrolytic oxidation, PEO）技术的复合涂层设计与制备、抗腐蚀性研究、抗菌/成骨/抗肿瘤功能研究以及体内生物学效应研究。. 在本项目的资助下，项目组发展了一系列基于PEO技术的复合涂层。通过调控水热时间，在镁合金表面成功地制备了能够有效封堵PEO孔洞的Mg-Al LDH涂层。该涂层在皮下植入40天，依旧可以保持结构的完整性，因此可以有效提高材料的抗腐蚀性能。此外，通过进一步引入生物活性的Zn离子，赋予了该复合涂层更好的成骨性能，以及抗菌性（可达99%）。项目组还在PEO改性镁合金表面制备了羟基氧化物（LDH前驱体）功能性复合涂层。PEO/MnOOH复合涂层表现出优异的自修复功能，能够极大地提升材料的抗腐蚀性能；PEO/FeOOH复合涂层具有良好的光热和光催化性能，能够在日光或者近红外光的辐射下，高效地杀死细菌，因而赋予材料抗感染功能，同时还能起到提高抗腐蚀性加速骨修复的作用。此外，项目组还发展了PEO/Mg-Mn LDH复合涂层，赋予材料良好的光热杀肿瘤性能。上述研究成果为镁合金的临床应用提供了实验基础和科学依据。