Highly Active Frozen Nanovesicles Microneedles for Senile Wound Healing via Antibacteria, Immunotherapy, and Skin Regeneration

Abstract Senile wound healing risks a variety of health complications and makes both economic and psychological burdens on patients greatly. Poor activity of aged dermal fibroblasts (A‐FBs) and local disordered immunoreaction in the deep dermis contribute to delayed wound healing. Therefore, the locally complex microenvironment in deep requires additional processing. Herein, a novel double‐layer hyaluronic acid methacrylate (HAMA)/polyvinyl alcohol (PVA) microneedle patch (MNP) coated by young fibroblast‐derived exosomes (Y‐EXOs) (Y‐EXOs@HAMA/PVA MNP) is presented for deep drug delivery, aged wound healing and immunoregulation. A spraying and freeze‐drying method is applied for keeping the bioactivity of the nanovesicles. An ideal loading of Y‐EXOs and enhanced strength for penetration have realized after circulation for times. The Y‐EXOs@HAMA/PVA MNP shows an excellent influence on delayed wound healing of aged skin with active A‐FBs, more deposition of collagen and less production of IL‐17A compared with application of aged fibroblast‐derived exosomes (A‐EXOs). Moreover, the content microRNAs in Y‐EXOs and A‐EXOs are sequenced for further study. This study initiatively demonstrates that Y‐EXOs have effective function on both anti‐aging and anti‐inflammation and Y‐EXOs@HAMA/PVA MNP is expected as a novel strategy for deep drug delivery for promoting hard wound healing in aged skin in future clinical application.