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

University Of California-Irvine, Irvine CA

Investigators

Abstract

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.