SHED-derived secretome promotes healing of Candida albicans-inoculated oral mucosal wounds in male rats through immunomodulatory and regenerative effects.

OBJECTIVE: This study evaluated the effects of topical human exfoliated deciduous teeth (SHED)-derived secretome on inflammatory, antimicrobial, and regenerative markers in Candida albicans-inoculated oral mucosal wounds. DESIGN: Thirty male Wistar rats were randomly assigned to receive SHED-derived secretome gel or 2.5% hydroxypropyl methylcellulose vehicle gel. Standardized oral mucosal wounds were inoculated with Candida albicans and treated topically three times daily. Tissue samples were collected on days 3, 7, and 10. Immunohistochemistry was used to assess TNF-α, IL-1β, IL-6, IL-10, β-defensin, VEGF, and FGF-2 expression. Data were analyzed using two-way ANOVA followed by Sidak's multiple-comparison test. RESULTS: Compared with the vehicle group, SHED-derived secretome significantly reduced TNF-α, IL-1β, and IL-6 expression at all time points. Conversely, IL-10 and β-defensin expression were significantly increased, indicating enhanced anti-inflammatory activity and innate antimicrobial defense. VEGF and FGF-2 expression were also significantly elevated, particularly on days 7 and 10, consistent with enhanced angiogenesis and tissue regeneration. Clinically, secretome-treated wounds showed faster ulcer resolution, reduced erythema, and improved re-epithelialization by day 10. CONCLUSION: Topical SHED-derived secretome promoted healing of Candida albicans-inoculated oral mucosal wounds by suppressing excessive inflammation while enhancing anti-inflammatory, antimicrobial, angiogenic, and regenerative responses. These findings support its potential as a cell-free therapeutic approach for infected oral mucosal wounds.