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

Adv Healthc Mater. 2024 May;13(12):e2304315. doi: 10.1002/adhm.202304315. Epub 2024 Feb 10.

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.

Keywords: aged wounds; bioactive storage; drug delivery; microenvironments; microneedles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exosomes* / chemistry
  • Exosomes* / metabolism
  • Fibroblasts* / metabolism
  • Humans
  • Hyaluronic Acid / chemistry
  • Immunotherapy / methods
  • Male
  • Mice
  • MicroRNAs / metabolism
  • Needles*
  • Polyvinyl Alcohol / chemistry
  • Regeneration / drug effects
  • Skin Aging / drug effects
  • Skin* / metabolism
  • Wound Healing* / drug effects

Substances

  • Hyaluronic Acid
  • Polyvinyl Alcohol
  • MicroRNAs