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

合成骨支架是多孔插入物，用于修复无法自行愈合的骨缺损，提供机械支撑，同时允许孔隙内的骨再生。 在用于制造的生物相容性材料中，磷酸钙陶瓷（CaP）因其硬度与骨骼相似而受到了极大的关注。该项目中考虑的材料系统由直接墨水写入制成的 CaP 支架组成，直接墨水写入是一种增材制造技术，通过该技术，胶体墨水棒沉积在交替的层中，然后进行烧结。 这些支架临床使用中的一个突出挑战是骨骼没有完全融入支架孔中。 现有支架设计方法中的两个限制阻碍了完整的骨整合：它们仅考虑由直杆制成的支架，并且它们不直接由骨整合措施驱动。 该奖项支持基础研究，以制定第一个计算框架，用于设计由曲线杆制成并由骨适应驱动的患者特异性 CaP 支架。 这项研究的结果有可能大幅提高用于修复大面积缺损的合成支架的临床可行性，为患者带来切实而显着的治疗和经济利益。 除了骨支架之外，这项研究还将推进可应用于相关材料系统的设计方法，例如骨科植入物中的多孔表面、细胞组织培养支架、颗粒过滤器和自修复材料。两个合作机构之间的本科生和研究生暑期交流将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进行推广。为了实现为具有空间变化架构的患者特异性骨支架制定第一个计算设计方法以实现完全骨再生的目标，该项目将拓扑优化技术与骨适应模拟相结合。特别是，该项目将 1）制定一个框架，以同时模拟骨支架系统内的骨适应，同时轻松适应支架设计的变化； 2）纳入适当的骨整合和支架强度测量，作为设计标准； 3）制定脚手架架构的设计表示，允许本地属性控制，同时确保可制造性。计算设计框架将通过设计的支架的材料和机械特性以及猪的体内研究进行验证。

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.