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支架，用于修复原本无法自行愈合的骨缺损，提供机械支持，同时允许毛孔内的骨再生。在用于其制备的生物相容性材料中，磷酸钙陶瓷(CAPS)因其具有与骨相似的硬度而备受关注。本项目中考虑的材料系统包括由直接墨水书写制成的盖子支架，这是一种添加剂制造技术，通过在交替的层中沉积胶体墨水棒，然后进行烧结。这些支架在临床应用中的一个突出挑战是缺乏骨与支架毛孔的完全结合。现有支架设计方法中的两个局限性阻碍了完全的骨整合：它们只考虑由直杆组成的支架，并且它们不是由骨整合的措施直接驱动的。该奖项支持基础研究，以制定第一个计算框架，用于设计由曲线杆制成的、由骨骼适配驱动的特定于患者的帽子支架。这项研究的结果有可能大幅提高合成支架修复大缺陷的临床可行性，为患者带来切实和显著的治疗和经济利益。除了骨支架，这项研究还将推进可应用于相关材料系统的设计方法，如骨科植入物中构建的多孔表面、用于细胞组织培养的支架、微粒过滤器和自我修复材料。这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提供服务。为了实现制定第一个针对患者的具有空间变化结构的骨支架的计算设计方法以实现完整的骨再生，该项目将把拓扑优化技术与骨适应模拟结合起来。特别是，这个项目将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的措施，以纳入作为设计标准；以及3)制定支架建筑的设计表示，允许在确保可制造性的同时进行局部财产控制。计算设计框架将通过所设计的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.