Regenerative and Dermal Wound Healing Activities of Bioactive Octapeptide

Cosmeceutical peptides (CPs), which modulate various biological activities, including skin regeneration and wound healing, have emerged as promising agents in skincare. In this study, we investigated the regenerative and wound healing potential of a short peptide, CP-02 (sequence CDARSDAR), using human dermal fibroblast cells (HDFs) in vitro and a zebrafish model in vivo. In HDFs, CP-02 treatment at concentrations of 50, 100, and 200 µg/mL significantly accelerated wound closure in a dose-dependent manner (p < 0.05) and upregulated the mRNA expression of CCND1, MYC, FGF2, EFG, and IL-8 at 12 h post-treatment. In amputated zebrafish larvae, exposure to CP-02 (5 µg/mL) for 72 h significantly increased fin regeneration, with a fin area of 3.5 mm2 and fin-fold length of 0.2 mm, compared with those in controls (2 mm2 and 0.07 mm, respectively). Intramuscular administration of CP-02 significantly improved the healing rates in wounded adult zebrafish to 58% and 76% on 12 and 16 days post wounding (dpw), respectively, compared with the vehicle (35% and 44%, respectively). Histological analysis (H&E staining) revealed reduced inflammatory cell infiltration, complete granulation, and re-epithelialization in the CP-02-treated tissues at 12 dpw. Furthermore, mRNA expression levels of tnf-α, il-1β, tgfb1, mmp9, mmp13, and timp2b were elevated in the CP-02 group at 4 dpw, whereas those of pro-fibrotic mediators, including acta2, ctgfb, cdh1, and col9a3 reduced in muscle tissue on 12 dpw. Collectively these findings demonstrate that CP-02 promotes effective, scar-reducing regeneration and wound healing, highlighting its strong potential as a therapeutic peptide for future skincare and cosmeceutical applications.