Collaborative Research: ISS: Real-time Sensing of Extracellular Matrix Remodeling during Fibroblast Phenotype Switching and Vascular Network Formation in Wound Healing

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Blood vessel formation and extracellular matrix (ECM) remodeling are intersecting processes in wound healing. The extent to which blood vessel formation and ECM remodeling are coordinated determines if wounds regenerate to functional tissue or form scars. The research objective is to understand the effects of microgravity on these wound healing processes in terms of the dynamic changes in gene and protein expression, structural changes in blood vessel formation, and ECM mechanical properties. This will be accomplished using a sensor-integrated tissue culture model that mimics a wound healing environment. This project advances a tissue characterization platform for both terrestrial- and space-based research. These experimental tools may also support the development of future therapeutics that target ECM remodeling and blood vessel formation for functional tissue regeneration during wound healing. The integrated educational objective is to create an interactive virtual educational platform for high-school and undergraduate biology students to improve interest and competency in engineering concepts and space-based biology research.Angiogenesis and extracellular matrix (ECM) remodeling are critical, intersecting processes in wound healing. The extent to which angiogenesis and ECM remodeling are spatially and temporally coordinated determines if wound healing leads to functional tissue regeneration or scar formation. The research objective of this project is to understand the effects of microgravity on wound healing processes in terms of the dynamic changes in fibroblast and endothelial cell (EC) gene and protein expression, structural changes in capillary networks during angiogenesis, and ECM mechanical properties. This will be accomplished using a sensor-integrated 3D co-culture model that mimics a wound healing environment via exogenous transforming growth factor beta stimulation. Hence, this project will leverage a new experimental platform to explore multi-scale interrelationships among gene and protein expression, endothelial network formation, and ECM mechanical properties in real-time. This project also generates dynamic profiles of vascular network formation and early wound repair in a novel in vitro wound healing environment that incorporates fibroblast-to-myofibroblast phenotypic transitions resulting from transforming growth factor beta stimulation. A significant advance contributed by this work will be the measurement of real-time ECM stiffening profiles resulting from key myofibroblast behaviors, including collagen production and contraction. Furthermore, this work provides new data regarding the impact of microgravity on fibroblast phenotypic switching, ECM stiffening, and vascular network formation using a 3D co-culture system. In summary, this project advances knowledge regarding the effects of microgravity on tissue remodeling processes during wound healing using autonomous tissue property sensing.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.