基于增材制造及可变形组件法的骨支架微结构仿生优化设计及性能研究

Recently there is an increasing demand for bone implant materials in clinic and the side effects of autologous/allogeneic bone extraction become prominent. Therefore, the demand for artificial bone scaffold becomes increasingly urgent, but there are still many problems to be solved in the current bone scaffolds. The feature of additive manufacturing (i.e. capability to manufacture personalized object with complex external and internal geometries) brings a good chance for the manufacturing of complex bone scaffold microstructure, and thus may greatly improve the mechanical and biological performance of current scaffolds. To meet the country's significant demands for 'Healthy China', in this project, we plan to investigate the bionic design of bone scaffold and its performance through imaging processing, structure optimization, numerical simulation and experimental testing. In particular, we plan to establish a new method for the bionic design of bone scaffold microstructure based on additive manufacturing and morphable component optimization framework, and establish a new method for the biodegradable scaffolds through considering the degradation of scaffold and the formation of new bones into the design stage. Then, we will investigate the influences of bone morphology, equivalent mechanical property, scaffold degradation and new bone formation on the scaffold microstructure design and the influence of new microstructure design on the scaffold performances. In the end of this project, we expect to have a new framework for designing additively manufacturable, bionic scaffolds whose performance are the best during their life time. The project will not only bring new ideas and approaches for the multiscale bionic design and additive manufacturing of artificial implants, but also will provide key techniques and fundamental basis for the development of bone repair discipline.

近年来随着临床对骨植入材料需求的日益增多及自体/异体取骨副作用的凸现，对人工骨支架的开发已经变得日益紧迫，但现有骨支架中还存在很多问题亟待解决。增材制造技术具有的制备个性化和复杂宏/微观结构的能力为骨支架的制备带来了新契机，利用该技术有望制备出性能优越的新支架。面向国家对健康中国的重大需求，本项目拟通过图像处理、结构优化、数值模拟和实验测试等多种技术手段研究骨支架微结构拓扑的优化设计，首先基于增材制造技术及可变形组件法建立骨支架微结构的仿生优化设计新框架，探讨骨骼形态特征、等效力学性能、支架降解及新骨生成行为与支架微结构的关联机制，利用增材制造制备设计的骨支架，揭示支架仿生微结构对支架强度、疲劳性能及渗透性等的影响机制，最终实现可增材制备的性能优越的骨支架微结构仿生设计新方法的建立。本项目的研究将为人工植入体的微结构拓扑仿生设计提供新思路，为骨修复学科的发展提供重要的关键技术及理论基础。

目前，我国每年有超过500万人次涉及骨移植置换手术，而且随着我国人口老龄化的加剧，各种复杂骨创伤及退变性骨疾病的发病率还在逐年增加，造成临床中对骨植入材料的需求日益增多。临床中，自体及异体骨仍是修复骨缺损的主要手段，但存在诸如供区并发症，疾病传染等凸显的副作用，使人工骨支架的需求变得日益紧迫，但现有的骨支架产品还存在诸如应力遮挡及服役期提前失效等严重问题。为了解决这些关键问题，本项目从产品的微结构调控出发，利用结构设计、数值计算、增材制造、图像分析及实验测试等多种手段展开了科学研究：首先，针对仿生骨支架设计阶段其基本构成单胞的选取无依据的问题，揭示了不同三次极小周期曲面（TPMS）仿生骨支架力学及生物学性能与其基本构成单胞之间的映射机理，给出了采用TPMS结构进行骨支架微结构设计时其基本单胞选择的重要依据及关键数据；其次，针对TPMS仿生骨支架的力学及生物学性能具有方向性的问题，采用弹性力学本构理论及均匀化方法建立了不同TPMS仿生骨支架各向异性弹性力学行为分析及表征的新方法，揭示了不同TPMS仿生骨支架各向异性力学行为与其基本构成单胞之间的关联机理，为TPMS骨支架的仿生优化设计提供了重要参考；最后，针对增材制备TPMS仿生骨支架存在的性能差异及其机理不明了的问题，建立了在三维空间中表征和分析增材制备仿生骨支架形貌差异的新方法，找到了其力学性能差异性的根本原因，为未来实现TPMS仿生骨支架的精准增材制造及产品的“设计-制备”一体化提供了关键的技术参考及重要数据，达到了项目预期研究目标。在项目执行期，以第一及通讯作者在Annals of Biomedical Engineering, Journal of Mechanical Behavior of Biomedical Materials等生物力学重要学术期刊上发表SCI论文12篇，图书章节1篇，主办国际学术研讨会1次，参加国内外学术会议8人次，并做特邀报告2人次，已授权国家发明专利2项，指导研究生6人（毕业3人），超额完成了项目制定的预期研究成果。