| NSF Org: |
CMMI Division of Civil, Mechanical, and Manufacturing Innovation |
| Recipient: |
|
| Initial Amendment Date: | July 27, 2020 |
| Latest Amendment Date: | July 27, 2020 |
| Award Number: | 2025362 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Wendy C. Crone
CMMI Division of Civil, Mechanical, and Manufacturing Innovation ENG Directorate for Engineering |
| Start Date: | September 1, 2020 |
| End Date: | August 31, 2024 (Estimated) |
| Total Intended Award Amount: | $400,000.00 |
| Total Awarded Amount to Date: | $400,000.00 |
| Funds Obligated to Date: |
|
| History of Investigator: |
|
| Recipient Sponsored Research Office: |
438 WHITNEY RD EXTENSION UNIT 1133 STORRS CT US 06269-9018 (860)486-3622 |
| Sponsor Congressional District: |
|
| Primary Place of Performance: |
181 Auditorium Rd Storrs CT US 06269-3247 |
| Primary Place of
Performance Congressional District: |
|
| Unique Entity Identifier (UEI): |
|
| Parent UEI: |
|
| NSF Program(s): |
Special Initiatives, Engineering of Biomed Systems, BMMB-Biomech & Mechanobiology |
| Primary Program Source: |
|
| Program Reference Code(s): |
|
| Program Element Code(s): |
|
| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.041 |
ABSTRACT
The human musculoskeletal system is sensitive to biomechanical cues. Mechanical stimulation is important to cartilage health. An absence of biomechanical loading causes articular cartilage to decay. Our natural cartilage has limited ability to repair itself. Therefore, it is a significant challenge to regenerate authentic cartilage tissue after it degenerates. On Earth, prolonged joint immobilization can cause cartilage degradation. In microgravity, the similar absence of biomechanical loading caused likely also damages cartilage tissue and cells. In this work, we will develop an engineered cartilage tissue construct to overcome the presumed degradation of cartilage in microgravity. This work will benefit life on Earth by improving our understanding of the effects of microgravity on cartilage. The results of this work may lead to new therapies to treat cartilage injuries. The results of this work will also benefit astronauts? health when they return to Earth. Furthermore, outcomes of this study will be used to introduce undergraduate and graduate engineering students to tissue engineering and nanomedicine. In addition, this work will increase diversity among biomedical engineers by encouraging underrepresented students to engage in science and engineering. Additional outreach activities are planned for middle/high school students and the general public.
Mechanical stimulation is critical to maintain chondrogenesis (differentiation into cartilage) and cartilage homeostasis (health maintenance); an absence of biomechanical loading results in degradation of articular cartilage. Because natural cartilage has limited self-repair ability, it is a significant challenge to regenerate authentic cartilage tissue after it degenerates. On Earth, prolonged joint immobilization can cause catabolic (breakdown) activities of chondrocyte and subsequent cartilage degradation. In space, the absence of biomechanical loading caused by microgravity most likely also damages chondrocyte function and cartilage homeostasis. If we can engineer a cartilage tissue construct to overcome the presumed degradation of cartilage in microgravity, it should also improve tissue engineering research and healthcare on Earth. This work will create a construct which can automatically supply itself with mechano-responsive microRNA as a therapy to restore cartilage cell chondrogenesis. The result will be a long-lasting (homeostatic) cartilage tissue construct to maintain cartilage cell chondrogenesis and homeostasis in the long term.
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.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
Note:
When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external
site maintained by the publisher. Some full text articles may not yet be available without a
charge during the embargo (administrative interval).
Some links on this page may take you to non-federal websites. Their policies may differ from
this site.
PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
Our engineered cartilage tissue was launched on February 1, 2024, aboard the NG-20 mission. Space Tango was our implementation partner. The mission was quite successful. We achieved all scientific goals. As a brief overview of outcomes, we observed that space microgravity disrupts homeostasis in engineered tissue, leading to cartilage tissue hypertrophy and then apoptosis. Furthermore, we found that the underlying mechanism was due to weakened cell-biomaterial substrate binding, which subsequently reduced mechanosignaling (e.g., TRPV4) and chondrogenesis (e.g., GAG synthesis).
In the NG-20 mission, for the first time, we developed a nanomaterial-based approach to counteract the adverse effects of space microgravity by strengthening cell-material interactions via beta integrin receptors. This enhanced integrin binding activated focal adhesion kinase (FAK) and TRPV4, along with downstream pathways, promoting chondrogenesis while inhibiting hypertrophy and apoptosis. Ultimately, we achieved successful cartilage tissue engineering in space.
Our findings hold significant implications for applications on Earth as well. Maintaining homeostasis in engineered or regenerated cartilage tissue over the long term is a key challenge in cartilage repair. Our findings suggest a novel strategy to enhance cartilage tissue engineering outcomes, offering potential improvements in regenerative medicine.
Moreover, the technological and engineering innovations, including the tissue construct design, will have practical applications on Earth. The project will also enrich education by serving as course material for introducing tissue engineering and nanomedicine to undergraduate and graduate students in a nanomedicine course designed and taught by the PI. Additionally, it will offer valuable research opportunities to students at both levels, promoting diversity by encouraging participation from underrepresented groups in science and engineering. Finally, the study will contribute to outreach efforts, inspiring middle and high school students and engaging the general public in scientific and engineering endeavors.
Last Modified: 01/05/2025
Modified by: Yupeng Chen
Please report errors in award information by writing to: awardsearch@nsf.gov.
