ISS: Engineering Scaffold-free, Biomimetic Neocartilage in Microgravity to Guide Terrestrial Tissue Engineering Strategies

ISS：微重力环境下的无支架仿生新软骨工程指导陆地组织工程策略

• 批准号: 2223365
• 负责人: Wendy Brown
• 金额: $ 39.97万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2223365&HistoricalAwards=false
• 关键词: ISS; Engineering; Scaffold; free; Biomimetic

Microgravity onboard the International Space Station (ISS) can replicate the conditions in which cartilage naturally forms in the body. Cartilage serves an important role in providing structural support and mechanical function throughout the body. Damage to cartilage causes pain and disability and lowers the quality of life for hundreds of millions of people worldwide. Once damaged, cartilage does not heal on its own. While some cartilage implants are already available, more progress must be made to create implants that replicate real cartilage structure and function, and that completely heal cartilage injuries. In this project, the key steps to creating cartilage implants will be studied in microgravity on the ISS to develop innovative engineering strategies that can be used on Earth. This project also includes the training of scientists from underrepresented backgrounds and the creation of outreach materials and activities to inspire grade-school students to be interested in tissue engineering in space.The objective of this project is to employ microgravity to enhance key steps in Earth-based cartilage tissue engineering. Current cartilage tissue engineering processes are limited by gravity and will therefore be investigated in the microgravity environment of the ISS. The investigators will examine the redifferentiation of expanded chondrocytes via aggregate rejuvenation. Single cell RNA-sequencing with pathway analysis will be used to identify genes that are differentially expressed by both articular chondrocytes (ACs) and costal chondrocytes (CCs) after redifferentiation in microgravity versus on Earth, as well between the cell types in each gravity condition. Gene targets will be identified to inform the development of Earth-based strategies to enhance chondrocyte redifferentiation. In addition, scaffold-free self-assembled neocartilage comprised of ACs and CCs will be engineered in microgravity and on Earth. The differences in cellular spacing, gene expression, matrix content, and mechanical properties of neocartilage generated in each gravity condition will elucidate mechanisms of neocartilage formation and molecular targets for neocartilage stimulation. Finally, tension-stimulated neocartilage maturation in microgravity will be assessed to elucidate mechanotransduction pathways for generating mechanically robust neocartilage. Overall, this work will contribute to the development of biomimetic tissue-engineered cartilage implants that will benefit millions of people who suffer from cartilage afflictions and to the understanding of cartilage development. Additionally, the understanding of cell and cartilage function in microgravity that will be obtained may also help develop fitness regimens to maintain astronauts’ cartilage health.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

国际空间站（ISS）上的微重力可以复制软骨在体内自然形成的条件。腕关节在提供整个身体的结构支撑和机械功能方面起着重要作用。软骨损伤会导致疼痛和残疾，并降低全球数亿人的生活质量。一旦受损，软骨不会自行愈合。虽然一些软骨植入物已经可用，但必须取得更多进展，以创建复制真实的软骨结构和功能的植入物，并完全治愈软骨损伤。在这个项目中，将在国际空间站的微重力环境下研究制造软骨植入物的关键步骤，以开发可在地球上使用的创新工程策略。该项目还包括对来自代表性不足背景的科学家进行培训，并编写宣传材料和开展宣传活动，以激发小学生对空间组织工程的兴趣，该项目的目的是利用微重力加强地球上软骨组织工程的关键步骤。目前的软骨组织工程过程受到重力的限制，因此将在国际空间站的微重力环境中进行研究。 研究人员将通过聚集体再生检查扩增的软骨细胞的再分化。将使用单细胞RNA测序和途径分析来鉴定关节软骨细胞（AC）和肋软骨细胞（CC）在微重力与地球上再分化后以及每种重力条件下细胞类型之间差异表达的基因。基因靶点将被确定，以告知地球为基础的战略，以提高软骨细胞再分化的发展。此外，由AC和CC组成的无支架自组装新软骨将在微重力和地球上进行工程设计。在每个重力条件下产生的新软骨的细胞间距，基因表达，基质含量和机械性能的差异将阐明新软骨形成的机制和新软骨刺激的分子靶点。最后，张力刺激的新软骨在微重力下的成熟将进行评估，以阐明机械转导途径，产生机械强大的新软骨。总的来说，这项工作将有助于仿生组织工程软骨植入物的发展，这将使数百万患有软骨疾病的人受益，并有助于了解软骨发育。此外，对微重力条件下细胞和软骨功能的理解也可能有助于开发健身方案，以保持宇航员的软骨健康。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。