CAREER: Engineering Functional Muscle-Tendon Structures using Scaffold-Free Cell-Based Directed Assembly and Theoretical Modeling

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0954990CorrThis integrated research and education CAREER proposal is focused to understand the role of fiber network architecture on overall tissue function, and thus establish the structure-function relationship. In the PI's scaffold-free approach, the natural ability of cells to grow and create their own extracellular matrix is harnessed, using geometric constraint, to form functional single fibers. This bottom-up approach will be utilized to create and tune fibers that will serve as building blocks for muscle-tendon structures, in which the architecture can be specified to fiber-level precision. The mechanical characterization of these muscle-tendon structures, when coupled with fiber-based theoretical modeling, will provide insight required to establish the structure-function relationship.The key novelties to this approach are: (1) scaffold-free engineering and mechanical evaluation of single fibers formed by directed cell growth, and (2) building functional muscle-tendon structures to precise fiber-level architecture. This represents a fundamental shift in tissue engineering approach; one necessary to create functional muscle-tendon units in which both muscle and tendon fiber architecture dictate the physiological and biomechanical function of the structure. This research program will utilize a scaffold-free approach to engineer muscle and tendon fibers by directing the growth of myoblasts and fibroblasts using geometric constraints to: (1) develop a fundamental understanding of the influence of environmental stimuli on cellular growth and fiber formation, in both muscle and tendon. (2) determine set(s) of bioreactor parameters for optimal muscle and tendon fiber performance(3) characterize the influence of fiber and crimp geometry on crimped engineered tendon fibers viscoelastic low-load and failure properties, using theoretical modeling and experimentation. (4) create functional muscle-tendon structures with fiber-level architectural fidelity to achieve the desired mechanical performance, as guided by theoretical modeling simulations.(5) establish the structure-function relationship for engineered muscle-tendon structures; including the contributions of each tissue, and compatibility at the muscle-tendon interface.The research will be complemented by integrated educational projects at the graduate, undergraduate and K-12 academic levels, both within Rensselaer Polytechnic Institute and as educational outreach. The latest research findings and methods will be incorporated into 3 graduate/undergraduate hybrid courses currently taught or co-taught by the PI, and a related 5-week lab experiment will be developed for the Cell & Tissue Engineering track of the Biomedical Engineering Laboratory course. Tissue engineering knowledge gained will be integrated into the PI's ongoing undergraduate (BIR Workshop) and K-12 (Design Your Future Day) outreach seminars. Furthermore, the PI will introduce a week-long biomaterials module into the summer American Society of Materials "Materials Day Camp", using an interactive series of hands-on experiments to establish the structure-function relationship of collagen networks present in soft tissues.