Nano-Encapsulated Spicule System Enhances Delivery of Wharton's Jelly MSC Secretome and Promotes Skin Rejuvenation: Preclinical and Clinical Evaluation.

Wharton's Jelly-derived mesenchymal stem cell (WJ-MSC) secretome contains diverse bioactive factors with potential for skin regeneration, but its clinical efficacy is limited by poor transdermal delivery. In this study, we developed a dual-delivery system by nanoencapsulating WJ-MSC secretome and coating it onto marine sponge-derived spicules. Physicochemical characterization, in vitro assays (fibroblast and keratinocyte proliferation, keratinocyte migration, type I procollagen secretion, and antioxidant activity), and in vivo penetration studies were conducted. A single-arm clinical trial evaluated dermal absorption, pore characteristics, skin texture, wrinkles, and pigmentation following topical application. Transdermal penetration efficiency was significantly higher in the nano-coated spicule group than in the uncoated secretome control. In vitro, secretome treatment promoted fibroblast and keratinocyte activity, accelerated wound closure, and increased collagen synthesis. Clinically, a single application enhanced dermal absorption and significantly reduced pore number, while two weeks of treatment decreased wrinkles and pigmentation. Spicule-based nanoencapsulation effectively overcomes the skin barrier, enhances the regenerative activity of WJ-MSC secretome, and induces measurable clinical improvements in skin rejuvenation. This platform represents a promising cosmetic and therapeutic strategy in dermatology.