Identification of a Novel Placental Peptide with Skin Reparative Properties by Cell-Surface Affinity Screening

Placental extracts are rich in bioactive molecules and exhibit broad reparative properties, yet the molecular constituents responsible for their effects on skin tissue repair remain insufficiently characterized. In this study, we employed a cell-surface affinity-based screening approach using dermal fibroblasts (BJ) and microvascular endothelial (HMEC-1) cells as dual biological baits to capture bioactive peptides directly from placental extracts. Through liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis and background subtraction, a peptide with dual-cell targeting potential, GPPVSE, was identified. In vitro, GPPVSE significantly promoted the viability, proliferation and migration of both BJ and HMEC-1 cells and enhanced endothelial tube formation. In vivo, topical 20 μM GPPVSE in a mouse full-thickness skin defect model achieved an 84.7% wound closure rate by day 8, outperforming both phosphate-buffered saline (PBS) and epidermal growth factor (EGF) groups. Histological analysis revealed that GPPVSE promoted granulation tissue maturation, strengthened epidermal–dermal junction integrity, and enhanced regeneration of skin appendages, including hair follicles and sebaceous glands, during the remodeling phase. Collectively, GPPVSE provides valuable molecular insights into the reparative activity of placental extracts and establishes a potentially adaptable cell-based paradigm for mining functional peptides from complex natural sources.