Composition/Functional Elasticity of Engineered Tissues

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DESCRIPTION: (provided by applicant) Tissue engineering is an emerging field in reconstructive surgery of dental and other craniofacial features consisting of skin, bone, or cartilage. In one common approach to tissue repair, cells capable of proliferating and synthesizing extracellular matrix (ECM) proteins are seeded on three-dimensional biodegradable polymer scaffolds. The scaffolds provide mechanical stability and geometric form to the construct until the cellular and biochemical components develop into competent tissue. In the design of engineered tissues, balancing the processes of biomaterial degeneration with tissue synthesis is critical in the initial phases of healing and long-term success. The combination of these two processes provides the mass and volumetric balance of materials that are intended to maintain the biological and mechanical health of repairing tissue. These complementary, time-dependent processes are often defined only empirically due to the lack of established parametric relationships. It is hypothesized that mathematical models can be developed to describe the dynamic mass state of concomitant scaffold degeneration and tissue synthesis. The model can be experimentally validated to confirm constituent quality and predict functional elastic parameters of the engineered tissue composite. The model will also provide design criteria and performance specifications to optimize the development of engineered tissues within the in vivo biologic and mechanical environment. It is intended that the general relationships defined in this project can be modified for all engineered tissue types. In the following proposal, two dynamic mass models (polyrmer and ECM mass) will be developed to define a construct elastic model of cartilage. These models will be directly validated through cell-culture and mechanical experiments. Poly-glycolic acid (PGA) scaffolds will be seeded with chondrocytes and cultured in vitro for up to 10 weeks. The polymer mass, ECM component masses (collagen and glycosaminoglycan), and elastic modulus of the constructs will be quantified at regular intervals. The results will be used to predict the time-dependent performance of cell-polymer constructs, and to gain insight into the mechanisms of scaffold degradation and ECM synthesis.