TITLE:
The Effects of Cyclic Stretch-Induced Cytoskeletal Reinforcement and Cell Alignment on the Cellular Wound Healing Processes
AUTHORS:
Kazuki Ikeda, Kazuaki Nagayama
KEYWORDS:
Cell Biomechanics, Mechanobiology, Cell Migration, Laser Ablation
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.2,
February
5,
2026
ABSTRACT: When biological skin tissue is damaged, the surrounding fibroblasts migrate to the wound to seal the damaged area and promote healing. In the fields of medicine and pharmacology, efforts have been vigorously pursued to understand the biochemical signaling pathways involved in wound healing and to develop wound healing promoters utilizing endogenous factors. In recent years, there has been an increased focus on the effects of mechanical stimuli on cells. Specifically, researchers have discovered that applying cyclic stretch stimulation to cells causes them to align in a specific direction, strengthening the structure of the actin cytoskeleton within the cells. Understanding how the physical environment and mechanical stimuli influence cellular migration during wound healing is also critically important for developing artificial tissues with high wound-healing and regenerative capabilities. Therefore, this study used cultured skin fibroblasts to prepare three groups of cell tissues: control cells with random orientation (CON), control cells with natural orientation (CON-OR), and cells with remarkable orientation induced by cyclic stretch stimulation (CSS-OR). These cell tissue groups were wounded using a pulsed laser, and cell migration during wound healing was observed using live-cell imaging. To analyze individual cell migration, cell nuclei were fluorescently visualized, and cell migration trajectories and speeds were quantified. The wound healing rate of the CON-OR group was faster than that of the CON group, suggesting that the cells migrate preferentially in alignment. In contrast, wound repair migration was suppressed in the CSS-OR group, even though the cells were oriented toward sealing the wound. Cyclic stretch stimulation markedly induced cell reorientation; however, it may have strengthened cell-cell and cell-substrate adhesions by significantly reinforcing the actin cytoskeleton, thereby suppressing the migration of individual cells immediately after wound formation.