Tensile forces stimulate vascular remodeling and epidermal cell proliferation in living skin

OBJECTIVES: To quantify tissue remodeling induced by static and cyclical application of tensional forces in a living perfused tissue. BACKGROUND: Cells are able to respond to mechanical cues from the environment and can switch between proliferation and quiescence. However, the effects of different regimens of tension on living, perfused skin have not been characterized. METHODS: The ears of living rats were mechanically loaded by applying tensile forces (0.5 Newtons) either statically or cyclically and then analyzing tissue responses using in vivo microscopy, immunohistochemistry, and corrosion casting. RESULTS: Quantitative immunohistochemistry showed that in the static group (4-day continuous tension) there was up to 4-fold increase in cellular proliferation in the epidermis after 4 days and a 2.8-fold increase in the vascularity in the dermis that peaked after 2 days. Comparable effects could be achieved in just 8 hours using a cyclic loading protocol. We also modeled the resultant stress produced in the ear using a linear finite element model and demonstrated a correlation between the level of applied stress and both epidermal cell proliferation and blood vessel density. CONCLUSIONS: Mechanical forces stimulate cell proliferation and vascular remodeling in living skin. As cell growth and vascular supply are critical to wound healing and tissue expansion, devices applying controlled mechanical loads to tissues may be a powerful therapy to treat tissue defects.