(Verbatim from the Applicant): Recently, immature cartilage from various sources has been found to undergo vigorous, and apparently complete repair in some cases. We recently found that fetal, newborn, and adult bovine articular cartilage has distinct biomechanical properties and integrative repair characteristics. During growth, the fixed charge (FC) per volume tissue was constant, whereas the collagen per volume tissue increased markedly. Together, these results suggest the overall working hypothesis that biomechanical regulation of collagen network (CN) metabolism during growth from fetus-to-calf-to-adult contributes to the evolution of articular cartilage composition and function. A corollary is that differential collagen network metabolism in fetal, post-natal, and mature articular cartilage underlie the distinct integrative repair characteristics of these tissues. The immediate objectives of this proposal are to test whether (1) bovine articular cartilage exhibits biomechanical properties that evolve during development (fetus-to-calf-to-adult) due to changes in CN composition and resultant alterations in the biomechanical function of both the CN and FC; (2) bovine articular cartilage function and composition evolve during growth (fetus-to-calf-to-adult) due to biosynthesis of the CN under the influence of dynamic compression; and (3) integrative repair of articular cartilage varies at different stages of growth because of changes in CN composition and metabolism as well as diffusion-reaction limitations. In (1), biomechanical, physicochemical, and biochemical analyses will be performed and the results analyzed to determine how FCD and CN contribute to the measured properties and what matrix components contribute to FCD and CN. In (2), explant cultures of fetal and calf cartilage will be incubated in vitro under free-swelling and mechanically loaded conditions, and examined for growth, as measured by the evolution of composition and function, and also CN biosynthesis. In (3), fetal, calf, and adult bovine cartilage explants will be incubated in various combinations to discriminate between cell and tissue factors, as mediators of integrative repair.
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