Hard-to-heal wounds, such as diabetic foot ulcers and pressure injuries, pose major clinical challenges due to chronic inflammation and cellular senescence. Cellular senescence-associated mechanisms, including stress-responsive p53/p21 signaling and senescence-associated secretory phenotype-related inflammation, contribute to impaired wound repair. We investigated whether local low-frequency vibration modulates wound healing and senescence-associated markers in tissues and exudates in a hyperglycemic rat full-thickness wound model, and whether treatment frequency affects its efficacy. A full-thickness wound model was established in hyperglycemic rats and local low-frequency vibration at 52 Hz was applied once or twice daily for 40 min (n = 5). The relative wound area was monitored, and molecular and histological analyses were performed on tissue samples and exudates to evaluate cellular senescence and the senescence-associated secretory phenotype. Local low-frequency vibration application twice daily significantly accelerated wound closure compared with that observed in the control group. Molecular and histological analyses revealed a reduction in the number of PTX3-positive cells and p53 expression in the twice-daily treatment group. Senescence-associated genes related to p53/p21 signaling, including Cdkn1a and Rb1, were downregulated in tissues and exudates. The number of p53-positive cells in exudate was lower in the twice-daily treatment group. In conclusion, local low-frequency vibrations enhanced wound healing and reduced the expression of senescence-associated markers and inflammatory mediators in tissues and exudates. These findings suggest that local low-frequency vibrations may act as a noninvasive, senomorphic physical therapy that modulates senescence-related pathways and inflammation, although future studies should determine whether local low-frequency vibrations further modulate senescence pathways.
