The high prevalence of osteoarthritis (OA) and the poor intrinsic healing capacity of articular cartilage has led to the development of cell-based strategies for cartilage repair. The initial granting period explored the novel application of physiologic deformational loading, a primary component of the chondrocyte physical enviornment in vivo, to precondition bovine chondrocyte-seeded 3D agarose hydrogel constructs in culture. Our goal has been to develop constructs with functional properties similar to the juvenile tissue from which the cells were derived. The two (2) most important insights that we have gained from our model agarose system are: (1) the application of physiologic deformational loading can promote development of constructs with better material properties than free-swelling controls only if sufficient nutrients are available; and (2) deformational loading may provide its beneficial effects on tissue construct growth via a mechanotransduction mechanism and/or solute transport mechanism. Building on our experience, we propose the following hypotheses: (1) Increasing concentration of amino acids in the culture media will promote development of constructs having higher material properties and protein content than constructs cultured basal amino acid levels. (2a) Unconfined compression will give rise to development of higher tensile modulus than compressive modulus in the radial direction (tension-compression nonlinearity), as well as higher tensile modulus in the radial direction compared to the axial direction (ansiotropy). The underlying mechanism reflects development of radial tensile strains during applied axial compressive loading. (2b) The unconfined compression loading configuration with a free impermeable platen and constraind lower impermeable platen will generate a lower Poisson's ratio (v) at the upper platen than at the lower platen. The underlying mechanism reflects the development of greater radial strains at the free upper platen that decreases to the confined lower platen. (3) Direct perfusion of medium through constructs will provide better material properties throughout the constructs, than free-swelling conditions. Direct perfusion and applied dynamic deformational loading will lead to synergistic effects on tissue growth. (4) Deformational loading will promote less construct surface roughness and better frictional properties than free-swelling constructs.
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