Award Abstract # 2223365
ISS: Engineering Scaffold-free, Biomimetic Neocartilage in Microgravity to Guide Terrestrial Tissue Engineering Strategies

NSF Org: CBET
Division of Chemical, Bioengineering, Environmental, and Transport Systems
Recipient: UNIVERSITY OF CALIFORNIA IRVINE
Initial Amendment Date: August 16, 2022
Latest Amendment Date: August 16, 2022
Award Number: 2223365
Award Instrument: Standard Grant
Program Manager: Steve Zehnder
szehnder@nsf.gov
 (703)292-7014
CBET
 Division of Chemical, Bioengineering, Environmental, and Transport Systems
ENG
 Directorate for Engineering
Start Date: September 1, 2022
End Date: August 31, 2025 (Estimated)
Total Intended Award Amount: $399,685.00
Total Awarded Amount to Date: $399,685.00
Funds Obligated to Date: FY 2022 = $399,685.00
History of Investigator:
  • Wendy Brown (Principal Investigator)
    wendy.brown@uci.edu
  • Kyriacos Athanasiou (Co-Principal Investigator)
Recipient Sponsored Research Office: University of California-Irvine
160 ALDRICH HALL
IRVINE
CA  US  92697-0001
(949)824-7295
Sponsor Congressional District: 47
Primary Place of Performance: University of California-Irvine
3131 Engineering Hall
Irvine
CA  US  92617-3213
Primary Place of Performance
Congressional District:
47
Unique Entity Identifier (UEI): MJC5FCYQTPE6
Parent UEI: MJC5FCYQTPE6
NSF Program(s): Special Initiatives
Primary Program Source: 01002223DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 070Z, 9102
Program Element Code(s): 164200
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

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.

Please report errors in award information by writing to: awardsearch@nsf.gov.

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