We propose the continuation of studies on the stress dependence of connective tissue. The cumulative data from our past efforts and those of others working in this field support the extension of Wolff's Law to fibrous connective tissue, cartilage and other support the extension of Wolff's Law to fibrous connective tissue, cartilage and other specialized connective tissue. Stress perturbations are seen to have profound effects on connective tissue hemostasis and on connective tissue repair. Current evidence on connective tissue homestasis and on connective tissue repair. Current evidence indicates that stress deprivation produces profound and rapid deterioration of fibrous connective tissue mechanical and structural properties due to increased matrix turnover and haphazard deposition of the newly synthesized fibrils. The recovery from this process roughly parallels its inception except at the insertion site. Insertion site weakness results from osteoclastic resorption of the ligament attachment fibers along with resorption of bone which is part of the osseous response to stress deprivation. Recovery from insertion site weakness appears to be a very slow process, requiring more than a year to overcome the changes induced in 2-3 mos. We proposed to complete the descriptive phases of this work using biochemical, histological and biomechanical tools and to develop a comprehensive theory of stress effects on connective tissue. It has become apparent that the fibrous tissues are not uniform in their anatomical, ultramorphological, biochemical or biomechanical characteristics. The ACL, for example, has been shown by our laboratory to be populated largely by cells with transmission electron microscopy (TEM) characteristics of fibrocartilaginous tissue rather than fibroblasts, as previously assumed. The implications of this finding are far reaching with respect to conceptual constructs dealing with repair and function of the anterior cruciate ligament (ACL). We have also observed profound differences in structure and composition of tendons as compared with ligaments, which lead us to the conclusion that more detailed analysis of individual structures is required with respect to stress enhancement or stress deprivation effects. A comprehensive theory cannot be developed by generalizing from single structures. Finally, the utility of a series of hyaluronic acid (HA) products for their efficacy in minimizing stress deprivation effects on the joint composite is proposed. HA has been observed to inhibit the physical and biochemical changes of contracture formation in a contracture model. The availability of a range of HA products makes the screening for efficacy a necessary and logical outgrowth of the earlier work.
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