ISS: Engineering Multiple-Compartment Cartilage Tissue Construct for Space and Terrestrial Applications

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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.