Tenocyte Mechanobiology in a Fiber Composite Mimetic

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Tendons are an important tissue for musculoskeletal function -- they connect muscles to bones. They are also a very slow healing tissue, due in part to the limited blood supply and small concentration of cells within the highly fibrous structure. If tendon cells, tenocytes, are going to be stimulated to enhance tendon growth and regeneration, it is vitally important that the understanding of how these cells respond to their mechanical environment is substantially increased. This project will use a combination of computer modeling and experimental studies to investigate how tenocytes respond to complex loading normally seen in a tendon. The work will focus on the micro-level -- in order to understand how variations in the mechanical environment just around the cell relate to the cellular response. In addition to advancing knowledge that will support future work in tissue engineering of tendons and other fibrous connective tissue, this project includes several educational and outreach activities. First, the research team will integrate students from high school through graduate school in order to help them understand the importance of research in this area and of integrating experimental and computational techniques. Next, there will be an opportunity for graduate students to travel to an international collaborator's laboratory to enhance their scientific preparation. Finally, hands-on workshops will be developed to provide participants with a broader understanding of connective tissue biomechanics.The overall objectives for this project are to: (1) determine the micromechanics and the type and magnitude of the local cellular strains as a function of fiber composite properties under physiologically relevant tensile strains; (2) determine tenocyte anabolic and catabolic metabolism as a function of the type and magnitude of the local cellular strains and the typed of integrin-ligand interaction; and (3) elucidate intracellular signaling pathways based on MAP kinase signaling that are involved in integratin-mediated mechanotransduction within tenocytes. This will be done through the development of a computational model of tenocytes within a fiber-reinforced structure and the validation of this model with experimental studies using a novel hydrogel-fiber composite mimetic that captures aspects of the tendon's fiber composite mechanics.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.