Many physiological and pathological processes, such as wound healing and tissue remodeling, are heavily influenced by continuous mechanical cell-cell and cell-ECM communication. Abnormalities that may compromise the biomechanical communication between the cells and the ECM can have significant repercussions on these physiological and pathological processes. The state of the mechanical environment and the reciprocal communication of mechanical signals between the ECM and the cell during wound healing and aged dermal tissue regeneration may be key in controlling the quality of the structure and physical properties of regenerated tissue.
This dissertation encompasses a series of studies developed for characterizing the effects of mechanical cues on altering and controlling tissue remodeling, and regeneration in the context of controlling scar formation during wound healing, and the maintenance and regeneration of the dermal extracellular matrix (ECM) during aging. In order to achieve this goal, in vitro models that contained some features of the provisional ECM, and the ECM of the dermis were developed and subjected to an array of quantifiable mechanical cues. Wound models were studied with different mechanical boundary conditions, and found to exhibit differences in initial short-term structural remodeling that lead to significant differences in the long-term synthesis of collagen after four weeks in culture. Dermal models seeded with fibroblasts from individuals of different ages were treated with a hyaluronic acid (HA)-based dermal filler. Changes in the mechanical environment of the dermal models caused by swelling of the hydrophilc HA, resulted in changes in the expression of mechanosensitive, and ECM remodeling genes, essential for the maintenance and regeneration of dermal tissue. Taken together, these data provide new insights on the role of mechanical signals in directing tissue remodeling.