Response of Human Skin Fibroblasts to Mechanical Stretch in Wound Healing Process Analyzed Using a Three-Dimensional Culture Model
Kaori Shikano, Keisuke Chiba, Shogo Miyata
Vol. 4 (2015) p. 170-178
Hypertrophic scars are frequently observed at wound sites that had been subjected to cyclical stretch stimuli, such as skin of the anterior chest wall and lower abdomen. Previous studies found that cyclic stretch modulated fibroblast infiltration and collagen fiber remodeling compared with static culture conditions. However, these studies used homogeneous cultures that poorly replicated the physiological organization at the wound site. Similar to early studies, we hypothesized that cyclic stretch modulated fibroblast infiltration and collagen fiber remodeling compared with static culture conditions. However, we replaced the homogeneous culture condition used in previous studies with a novel two gel wound model consisting of an inner decellularized collagen gel mimicking the wound site and an outer fibroblast gel simulating the epidermis. These models were then subjected to either 1-Hz uniaxial cyclical stretch for 3 h each day or were placed under static culture conditions. After day 4 in culture, we found two significant differences between specimens under the cyclic stretch conditions and those under static conditions. First, there were fewer fibroblast infiltrates in the inner wound-mimicking gel in cyclically stretched specimens than in statically stretched specimens. Second, the microstructure and orientation of collagen fibers in cyclically stretched specimens differed histologically from those in static culture. These results add to the growing evidence that cyclical stretch modulates the wound-healing process.