掺锂微孔化的3D全多孔聚醚醚酮通过调控巨噬细胞免疫微环境促进骨缺损修复的机制研究

从免疫调控角度出发对生物材料进行改性，营造利于骨修复的免疫微环境，最终提高材料的骨缺损修复能力是近期骨修复材料的研究热点。但以低弹性模量的材料为研究对象且同时对材料的结构和成分进行改性，从而营造促成骨的免疫微环境，以达到“免疫成骨”效应的研究鲜有。本研究拟以具有力学优势但因成骨活性差而限制其广泛使用的聚醚醚酮（PEEK）为研究对象，在制备内部孔隙连通的3D全多孔PEEK的前提下对其进行结构及成分改性，制备具有“直接成骨”及“免疫成骨”效应的掺锂微孔化全多孔PEEK。并通过体内外实验，验证掺锂微孔化全多孔PEEK可通过表面微结构和局部微环境释放双重免疫调节诱导巨噬细胞向M2型极化，营造成骨的免疫微环境，从而促进骨修复的假说。同时利用分子生物学实验研究该材料调节免疫的可能机制，为掺锂微孔化全多孔PEEK在骨修复领域的推广奠定基础。

It is the hotspot to modify biomaterials to develop an immunological osteogenic microenvironment for bone regeneration. However, few researches simultaneously focused on the combination of structure and composition modification to achieve the "immunological osteogenesis" effect about low-modulus materials. Herein, we aim to prepare a lithium-doped 3D porous polyetheretherketone (PEEK), a mechanical friendly and poor osteogenic material, with microporous surface, to render porous PEEK "direct osteogenesis" and "immunological osteogenesis" effect. The immunomodulation ability of lithium-doped porous PEEK with microporous surface will be examined by both in vitro and in vivo experiments. The hypothesis that surface microstructure and local microenvironment around lithium-doped porous PEEK with microporous surface can induce macrophages polarizing to M2 phenotype, then generating an osteogenic microenvironment will be verified through in vitro and in vivo experiments. Finally, in vitro molecular biological experiments will be carried out to verify the specific mechanism of its immunomodulation ability, which will advance further clinical application of lithium-doped porous PEEK in bone repair.