The studies described herein examine the collagenous extracellular matrix and attempt to characterize changes in tissue behavior, due to damage and disuse, by utilizing techniques of engineering and biology. To present such information, this dissertation has been organized in three major sections. The first section examines collagen microstructural morphology and organization in normal tendon and ligament, and the microstructural organization of collagen at the interface between scar and residual tissue during healing. Results of this work lend insight into the developing collagenous matrix, the continuity of collagen fibrils in tissues from skeletally mature animals, and the mechanisms by which force might be transferred from disorganized scar tissue to intact residual collagen fibrils. In the second section, changes in normal and healing collagenous extracellular matrices due to disuse are examined. This work indicates that the cystein proteinase, cathepsin K, may play a substantial role in collagen degradation during disuse, that significant reductions in the material properties of the collagenous extracellular matrix occur with disuse that are likely caused by altered collagenous scar tissue organization, and that administration of insulin-like growth factor-I or insulin-like growth-factor-I plus growth hormone significantly increase the material properties of the tissue;​ restoring mechanical deficits due to disuse. In the third section, the effects of introducing a sub-failure stretch into the collagenous extracellular matrix are explored. Results indicate a threshold for tissue damage exists in ligament, and fibroblast necrosis occurs with increasing tissue strain, which may be followed by apoptosis. In addition, this tissue damage results in decreased material properties and laxity that recover more quickly in tissues from skeletally immature animals. Further, microscopic examination of collagen fiber and fibril rupture and quantitative analysis o f collagen, proteoglycan, and proteinase mRNA levels after a damaging subfailure stretch and subsequent healing are explored. Therefore, in summary, these studies examine collagenous extracellular matrices under a wide range of circumstances, and report changes in fibroblast behavior, collagen structure and organization, and mechanical integrity as result of various stimuli and conditions.