The applicability of Wolff's law to connective tissue other than bone has become increasingly evident in recent years. Current evidence suggests that stress deprivation effects on soft tissues are profound and occur rapidly; where the recovery from stress deprivation is quite slow. In this respect, recovery seems to parallel the effects of exercise on normal connective tissue. For example, our studies indicate that a large effort over a long period of time is required for a small hypertrophy increment of tendons or ligaments. The purpose of the proposed research program is to document more completely: 1) the fibrous connective tissue morphological and molecular changes resulting from stress deprivation, and 2) the consequent alteration in physical characteristics. The answers to these questions are particularly important with respect to the development of the rationale for treatment and rehabilitation of soft tissue injuries, such as the knee ligaments, etc. A standard internal fixation model will be used to induce stress deprivation effects in rabbit knees. Capsular and ligamentous structures from the model will be characterized by biomechanical, morphological, biochemical and metabolic techniques on a progressive time base during the development of and during recovery from the stress deprivation state. Preliminary results indicate the need to follow the animals for more than one year because of the slow recovery rate. Finally, hormone or drug treatment effects will be evaluated for efficacy in modulating the development and recovery from the stress deprivation state. Biochemical analyses to be employed will permit evaluation of collagen turnover, total proteoglycans, and collagen cross-link quantitation (reducible and non-reducible). Light microscopy and transmission EM will be used to characterize matrix and cells, as well as the ligament insertion sites. Biomechanical tests will yield data on ultimate strength and stiffness of bone-ligament-bone complex, as well as the mechanical properties of the ligament substance. In addition, arthrographic characterization of contracture strength will also be performed.