镁激励聚乳酸人工骨降解的正反馈调控机理及其3D打印制备研究

Polylactide (PLA) has good biocompatibility and processibility, but its degradation rate is too slow and degradation intermediate products are acidic, which limit its application in bone defect repair. In this project, laser 3D printing technology is applied to fabricate PLA artificial bone with positive feedback regulatory function. In detail, the alkaline product generated by magnesium degradation is used to neutralize the acidic environment producted by polylactic acid degradation. It consume the degradation products of PLA and lead the degradation to the forward reaction direction. Thereby, a positive feedback loop is formed to accelerate the degradation of PLA. The project aims to study the mechanism and characteristics of sintering and mass transfer of PLA during the forming process, including viscous flow, interfacial diffusion, evaporative coagulation and so on. Meanwhile, the formation causes and inhibition strategies of defects including carbonation and burning, foaming and cracking, warpage and deformation will be studied. It's focused on studying the influence of the component content and dispersion state of magnesium on the loss of artificial bone and pH of solution during degradation. The positive feedback loop formation conditions and regulatory strategies of magnesium accelerated artificial bone degradation are revealed, and the action mechanisms of degradation products on cell adhesion, proliferation, differentiation and bone regeneration are analyzed. The correlation rules and optimization criteria between structural parameters of polymer, processing parameters of artificial bone, pore structure and the mechanical and biological properties of artificial bone are investigated. The project aims to provide theoretical support and scientific basis for the development of artificial bone manufacturing technology with independent intellectual property rights.

聚乳酸具有良好的生物相容性和加工性，但降解速率过慢且中间产物呈酸性，限制了其在骨缺损修复中的应用。本项目拟利用激光3D打印技术制备具有正反馈降解调控功能的聚乳酸人工骨，具体是利用镁降解生成的碱性产物中和聚乳酸降解产生的酸性环境，消耗聚乳酸的降解产物使其降解向正反应方向进行，从而形成正反馈循环加快聚乳酸降解。研究成型过程中聚乳酸的粘性流动、界面扩散、蒸发凝聚等烧结传质机理及特性，查明人工骨的碳化与烧损、起泡与开裂、翘曲与变形等缺陷形成原因及抑制策略；重点研究镁的组分含量、分散状态等对降解过程中人工骨质量损失、溶液酸碱度等的影响规律，揭示镁加速人工骨降解的正反馈循环形成条件及调控策略，分析降解产物对细胞粘附、增殖、分化等行为及骨组织再生的作用机制；探明高分子结构参数、人工骨制备工艺和孔隙结构与力学和生物学性能的关联规律及优化准则，为开发具有自主知识产权的人工骨制造技术提供理论支撑和科学依据。

损伤与修复、缺失与再生一直是人类无限追求和不断探索的世界性难题，特别是随着意外创伤的增加和人口老龄化的加剧，对人工骨植入物的需求日益增长。聚乳酸（PLA）具有良好的生物相容性和加工性，但降解速率过慢且中间产物呈酸性，限制了其在骨缺损修复中的应用。镁（Mg）具有较低的标准电极电位，在生理环境中容易降解产生碱性环境，可加快PLA的降解。为此，本项目利用Mg降解产物呈碱性的特点构建加速PLA降解的正反馈循环，并利用激光3D打印技术制备具有个体化外形和可控内部多孔结构的PLA人工骨，主要研究内容如下：.研制了面向Mg/PLA复合人工骨支架制备的激光3D打印系统，开展了不同工艺组配下复合人工骨的激光烧结工艺实验，研究了激光作用下PLA的粘性流动、界面扩散、蒸发凝聚等烧结传质机理及特性，发现粉末颗粒的表面张力是促进烧结进行的驱动力，同时平衡颗粒固有的粘性阻力，进一步通过粉末颗粒的面积变化率、体积变化率和能量平衡方程推导出以致密化速率表达的烧结速率方程；查明了激光3D打印工艺参数对人工骨成形质量的影响规律及调控策略，发现各工艺参数对压缩强度的影响程度由大到小依次为激光功率＞扫描速度＞光斑直径＞扫描间距，即激光功率是影响支架力学性能的最重要因素，最优的工艺参数组合为激光功率2.25 W，光斑直径50 μm，扫描速度100 mm·s-1以及扫描间距1 mm；研究了复合人工骨的质量损失情况、溶液的离子浓度和酸碱度变化，揭示了Mg加速PLA人工骨降解的正反馈系统形成条件及调控策略，发现Mg降解产生的碱性产物Mg(OH)2可以中和PLLA降解的酸性产物，消耗降解产物使其降解向正反应方向进行，从而形成正反馈循环加快骨支架降解。此外Mg降解释放的Mg2+也能够促进细胞在支架上的粘附和增殖。.以上研究成果以第一/通讯作者发表SCI论文27篇，其中TOP期刊论文15篇，影响因子10.0以上8篇，入选ESI高被引论文8篇，ESI热点论文2篇，授权国家发明专利2项，获得科技奖励3项；培养硕士研究生生8人，作国内外学术会议报告10次，其中优秀报告2次。