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）的船上微重力可以复制软骨在体内自然形成的条件。软骨在整个身体提供结构支持和机械功能方面起着重要作用。软骨的损害会导致疼痛和残疾，并降低全球数亿人的生活质量。一旦损坏，软骨就不会自行愈合。虽然已经有一些软骨的凹痕，但必须取得更多的进展，以创造出复制真实软骨结构和功能的垂体，并完全治愈软骨损伤。在这个项目中，将在ISS上的微重力研究创建软骨的关键步骤，以制定可在地球上使用的创新工程策略。该项目还包括培训来自代表性不足的背景的科学家，以及创建外展材料和活动，以激发年级学生对太空中的组织工程感兴趣。该项目的目的是利用微重力来增强基于地球的软骨组织工程的关键步骤。当前的软骨组织工程过程受重力的限制，因此将在IS的微重力环境中进行研究。研究人员将通过骨料修订研究扩大软骨细胞的扩展。通过途径分析的单细胞RNA序列将用于鉴定由关节软骨细胞（ACS）和肋骨软骨细胞（CC）差异表达的基因，在重新分化微重力与在地球上的细胞类型之间以及细胞类型之间的细胞类型之间的重新分化。将确定基因靶标，以告知基于地球的策略以增强软骨细胞的重新分化。此外，由ACS和CC组成的无脚手架的自组装的新机构将在微重力和地球上进行设计。在每种重力条件下产生的新轨道的细胞间距，基因表达，基因表达，基因表达，基因含量和机械性能的差异将阐明Neocartilage形成的机制和新科托尔模拟的分子靶标。最后，将评估微重力中的张力刺激的新能力成熟，以阐明生成机械稳健的新科丁氏菌的机制。总体而言，这项工作将有助于仿生组织工程软骨实施的发展，这将使数百万患有软骨感情的人受益以及对软骨发展的理解。此外，对将获得的细胞和软骨功能的理解也可能有助于开发健身方案，以维持宇航员的软骨健康。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛的影响审查标准通过评估来评估的。