Collaborative Research: Bone Adaptation-Driven Design of Scaffolds with Spatially-Varying Architecture for Enhanced Growth

合成骨支架是一种多孔的植入物，用于修复无法自行愈合的骨缺损，提供机械支撑，同时允许骨在孔隙内再生。在生物相容性材料中，磷酸钙陶瓷（CaPs）因其刚度与骨相似而受到广泛关注。在这个项目中考虑的材料系统包括由直接墨水书写（Direct Ink Writing）制成的CaP支架，这是一种增材制造技术，通过这种技术，胶体墨水棒交替沉积并随后烧结。在临床使用这些支架的一个突出的挑战是缺乏完全整合骨到支架孔。现有支架设计方法的两个限制阻碍了完全的骨整合：它们只考虑由直杆制成的支架，并且它们不是由骨整合的测量直接驱动的。该奖项支持基础研究，以制定第一个计算框架，用于设计由曲线棒制成的由骨适应驱动的患者特异性CaP支架。本研究结果有可能大幅提高合成支架用于大缺损修复的临床可行性，为患者带来切实而显著的治疗和经济效益。除了骨支架外，这项研究还将推进可应用于相关材料系统的设计方法，如骨科植入物的多孔表面、细胞组织培养支架、颗粒过滤器和自愈材料。两所合作院校将于夏季交换本科生和研究生，为下一代材料设计师提供培训机会。该奖项还将支持通过夏令营向高中生提供服务。为了实现为完全骨再生的具有空间变化结构的患者特异性骨支架制定第一个计算设计方法的目标，该项目将拓扑优化技术与骨适应模拟相结合。具体而言，本项目将1)制定一个框架，既能在骨-支架系统内模拟骨适应，又能随时适应支架设计的变化；2)纳入足够的骨整合和支架强度措施作为设计标准；3)制定脚手架结构的设计表示，在确保可制造性的同时，允许本地属性控制。计算设计框架将通过所设计支架的材料和机械特性以及在猪体内的研究来验证。

Synthetic bone scaffolds are porous inserts used to repair bone defects that would not otherwise heal on their own, providing mechanical support while allowing bone regeneration inside the pores. Among the biocompatible materials used for their fabrication, calcium phosphate ceramics (CaPs) have received significant attention because their stiffness is similar to that of bone. The material system considered in this project consists of CaP scaffolds made by Direct Ink Writing, an additive manufacturing technique whereby rods of a colloidal ink are deposited in alternating layers and subsequently sintered. An outstanding challenge in the clinical use of these scaffolds is the lack of complete integration of the bone into the scaffold pores. Complete osteointegration is hindered by two limitations in existing scaffold design methods: they only consider scaffolds made of straight rods, and they are not directly driven by a measure of bone integration. This award supports fundamental research to formulate the first computational framework for the design of patient-specific CaP scaffolds made of curvilinear rods and driven by bone adaptation. Results of this research have the potential to substantially increase the clinical viability of synthetic scaffolds for large defect repair, with tangible and significant treatment and financial benefits for patients. In addition to bone scaffolds, this research will advance design methodology that may be applied to related material systems, such as architected porous surfaces in orthopedic implants, scaffolds for cell tissue culture, particulate filters and self-healing materials. A summer exchange of undergraduate and graduate students between the two collaborating institutions will provide training opportunities for the next generation of material designers. This award will also support outreach to high school students via summer residential camps. To achieve the goal of formulating the first computational design methodology for patient-specific bone scaffolds with spatially-varying architecture for complete bone regeneration, this project will couple topology optimization techniques with bone adaptation simulation. In particular, this project will 1) formulate a framework to simultaneously model bone adaptation within the bone-scaffold system while readily accommodating changes in the scaffold design; 2) incorporate adequate measures of osteointegration and scaffold strength to incorporate as design criteria; and 3) formulate a design representation of the scaffold architecture that allows for local property control while ensuring manufacturability. The computational design framework will be validated via material and mechanical characterization of scaffolds designed, and via an in vivo study in pigs.