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

协作研究：具有空间变化架构的骨骼适应驱动支架设计，以促进生长

• 批准号: 1727591
• 负责人: JULIAN NORATO
• 金额: $ 28.43万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1727591&HistoricalAwards=false
• 关键词: Collaborative; Research; Bone; Adaptation; Driven

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.

合成骨支架是用于修复骨缺损的多孔插入物，否则骨缺损不会自行愈合，提供机械支撑，同时允许骨在孔隙内再生。 在用于其制造的生物相容性材料中，磷酸钙陶瓷（CaP）受到了极大的关注，因为它们的刚度与骨的刚度相似。该项目中考虑的材料系统由直接墨水书写制成的CaP支架组成，直接墨水书写是一种增材制造技术，其中胶体墨水的棒以交替层沉积并随后烧结。 这些支架的临床应用中的突出挑战是骨不能完全整合到支架孔中。 现有支架设计方法的两个局限性阻碍了完全的骨整合：它们仅考虑由直杆制成的支架，并且它们不直接由骨整合的测量驱动。 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大提高合成支架用于大缺损修复的临床可行性，为患者带来切实和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，例如骨科植入物中的建筑多孔表面，细胞组织培养支架，颗粒过滤器和自愈合材料。两个合作机构之间的本科生和研究生夏季交流将为下一代材料设计师提供培训机会。该奖项还将通过夏令营支持高中生的外联活动。为了实现为患者特定的骨支架制定第一个计算设计方法的目标，该支架具有完全骨再生的空间变化结构，本项目将结合拓扑优化技术和骨适应模拟。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性，同时容易适应支架设计的变化; 2）纳入骨整合和支架强度的适当措施，以作为设计标准; 3）制定支架结构的设计表示，允许局部属性控制，同时确保可制造性。计算设计框架将通过设计支架的材料和机械表征以及猪体内研究进行验证。

项目成果

Bone Adaptation-Driven Design of Periodic Scaffolds

骨适应驱动的周期性支架设计

• DOI: 10.1115/1.4050928
• 发表时间: 2021
• 期刊: Journal of Mechanical Design
• 影响因子: 3.3
• 作者: Cohen, David O.;Aboutaleb, Sohaila M.;Johnson, Amy Wagoner;Norato, Julian A.
• 通讯作者: Norato, Julian A.

Computational Design of Additively Manufactured Curvilinear Scaffolds for Bone Repair

用于骨修复的增材制造曲线支架的计算设计

• DOI: 10.1115/detc2022-90582
• 发表时间: 2022
• 期刊: International Design Engineering Technical Conferences and Computers and Information in Engineering Conference
• 作者: Cohen, David O.;Aboutaleb, Sohaila M.;Wagoner Johnson, Amy;Norato, Julian A.
• 通讯作者: Norato, Julian A.

Direct process feedback in extrusion-based 3D bioprinting

• DOI: 10.1088/1758-5090/ab4d97
• 发表时间: 2020-01-01
• 期刊: BIOFABRICATION
• 影响因子: 9
• 作者: Armstrong, Ashley A.;Norato, Julian;Johnson, Amy J. Wagoner
• 通讯作者: Johnson, Amy J. Wagoner