Combined compound betamethasone and 595 nm pulsed dye laser improves hypertrophic scar and is associated with enhanced autophagy in myofibroblasts

Compound betamethasone combined with 595 nm pulsed dye laser (PDL) is widely used in the clinical management of hypertrophic scars. However, the mechanisms underlying this enhanced effect remain poorly understood. This study evaluated its therapeutic efficacy and investigated whether induction of autophagy in myofibroblasts is associated with scar improvement. A rabbit ear hypertrophic scar model was established and divided into control, compound betamethasone injection (BI), PDL, and combined (BI + PDL) groups. Scar morphology and histological changes were assessed. Autophagy was evaluated using transmission electron microscopy (TEM) and immunohistochemical detection of LC3B and p62. In vitro, hypertrophic scar-derived myofibroblasts were treated with betamethasone dipropionate (BD), PDL, or their combination (BD + PDL). Cell viability, collagen expression, and autophagic activity were analyzed using CCK-8 assays, Western blotting, MDC staining, immunofluorescence, and TEM. Chloroquine was used to assess autophagic flux. The combined BI + PDL treatment produced the most pronounced improvement in scar architecture, with reduced collagen deposition, decreased microvessel density, and increased number of apoptotic cells. Autophagy levels were significantly elevated in the combination group both in vivo and in vitro. In cultured myofibroblasts, BD + PDL markedly inhibited cell viability and reduced type I and type III collagen expression. This effect was accompanied by increased autophagosome formation, an elevated LC3II/LC3I ratio, and decreased p62 expression. Importantly, inhibition of autophagic flux with chloroquine attenuated the collagen-suppressive effect of the combined treatment. Compound betamethasone combined with 595 nm PDL significantly improves hypertrophic scars, an effect associated with enhanced autophagic activity in myofibroblasts which may partly mediate collagen degradation.