We are excited to share that we received a 5 year NIH R01 from NIAMS to explore the mechanotransduction pathways that regulate hierarchical collagen fiber formation!!!
Collagen fibers are the primary source of strength and function in tissue throughout the body, particularly in tendons, ligaments, and menisci. Cells organize these fibers hierarchically, assembling them from nm-wide fibrils, into larger fibers and fascicles, growing in size and strength with increasing mechanical demand. Injuries disrupt this organization, resulting in loss of function, pain, and decreased mobility. Unfortunately, these collagen fibers do not regenerate after injury, nor in engineered replacements, creating a lack of repair options for torn tendons, ligaments, and menisci. Our long-term goal is to understand how cells regulate this fiber formation so to engineer functional replacements and drive repair in vivo after injury. As a step toward this goal, this grant will explore how mechanical cues transmitted via cellular contraction and stretch-activated ion channels regulate ligament fibroblast's development of hierarchical fibers. In particularly, we will be exploring how cellular sensing via FAK, TRPV4, and Piezo1 regulate tissue maturation at the fibril, fiber, and fascicle length-scale. Special thanks to the students that have made this grant possible with all their excellent preliminary work and our collaborators, Drs. Rene Olivares-Navarrete and Hank Donahue!
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