PEEK骨植入材料表面BMP-2基因缓释系统的构建及其促成骨作用研究

Titanium and its alloys are the most common biomaterials in the field of bone defect repair because of good mechanical properties and biological activity, but its high elastic modulus can easily lead to bone resorption. In order to improve the long-term therapeutic effect of bone defect repair, it is very important to develop a new bone graft material with ideal elastic modulus and mechanical properties and the ability to promote bone regeneration. During the preliminary research, we have synthesized the PEEK-based nano-biomimetic composites with excellent mechanical properties. Plasma Immersion Ion Implantation (PIII) is a novel surface modification method, which can not only prepare nanoscale topological morphology, but also construct nitrogen-containing functional groups in situ. In this study, we prepared the amino acid modification of microspheres on the basis of PLGA microspheres containing BMP-2 gene, and then rely on the "wet bonding properties" of PDA and its chemical bonding with PEEK surface functional groups to build a PDA bionic coating on the surface of PEEK. The BMP-2/PLGA microspheres with amino acid modification will bound to the surface of PEEK by graft polymerization. Using the BMP-2 gene to target the transfection of the target cells, the host cells are induced to express the osteogenic genes and promote the rapid binding of the implant and the bone tissue. In addition, this study will also carry out a comprehensive and systematic review of the transduction efficiency of BMP-2 gene and the biological activity of modified PEEK surface, and lay a solid foundation for the construction of PEEK implant carrying therapeutic gene.

钛及钛合金具有良好的力学性能和生物活性，是骨缺损修复领域最常用的生物材料，但其过高的弹性模量容易导致周围骨质吸收。为提高骨缺损修复的远期治疗效果，研制具有理想弹性模量和力学性能，且可促进骨再生的新型植骨材料至关重要。在前期研究工作中，我们率先合成了具有优异力学性能的PEEK基纳米仿生复合材料；对其进行氮气PIII改性，不仅可以制备纳米级拓扑形貌结构，而且原位构建了含氮功能基团。本研究拟在制备载BMP-2基因PLGA微球的基础上，对微球进行氨基化修饰，再依靠PDA自身的“湿粘接特性”在其表面构建PDA仿生涂层；通过接枝聚合反应，将氨基化载基因微球牢固地结合于PEEK表面。利用BMP-2基因对靶细胞的转染，诱导宿主细胞表达成骨基因，促进植入体与骨组织的快速结合。此外，本研究还将对BMP-2基因的转导效率，以及改性表面的生物活性进行全面、系统评价，为构建携带治疗基因的PEEK植入体奠定坚实基础。

钛及钛合金具有良好的力学性能和生物活性，是骨缺损修复领域最常用的生物材料，但其过高的弹性模量容易导致周围骨质吸收。为提高骨缺损修复的远期治疗效果，本项目围绕PEEK骨植入材料表面载基因微球改性对骨结合的影响开展研究。在制备载BMP-2基因PLGA微球的基础上，对微球进行了氨基化修饰，并依靠PDA自身的“湿粘接特性”在其表面构建了PDA仿生涂层；通过接枝聚合反应及物理效应，将载基因微球牢固地结合于PEEK表面；研究了(PLGA-NH2@pBMP-2)-PEEK 植入材料对骨髓间充质干细胞增殖、分化和功能的影响；自主设计了 PEEK 口腔种植体和相关的种植器械，通过建立比格犬下颌牙列缺损模型，综合评估了NPEEK-PDA-(PLGA-NH2@pBMP-2)植入材料的体内成骨活性。结果成功地构建了载PLGA-NH2@pBMP-2微球的PEEK缓释植入材料，改善了PEEK表面形貌、粗糙度和亲水性，提高了材料的生物相容性和体内外成骨活性。综上，我们完成了本课题的科学假设并基本达到预期目标，初步实现了从基因层面调控PEEK的成骨活性，具有一定的临床应用潜能，为构建携带治疗基因的PEEK植入体奠定了坚实的理论基础。