Hyaluronic acid-modified and verteporfin-loaded polylactic acid nanogels promote scarless wound healing by accelerating wound re-epithelialization and controlling scar formation

J Nanobiotechnology. 2023 Jul 26;21(1):241. doi: 10.1186/s12951-023-02014-x.

Abstract

Wound healing is a common occurrence. However, delayed healing and aberrant scarring result in pathological wound healing. Accordingly, a scarless wound healing remains a significant clinical challenge. In this study, we constructed hyaluronic acid (HA)-modified and verteporfin (VP)-loaded polylactic acid (PLA) nanogels (HA/VP-PLA) to promote scarless wound healing by accelerating wound re-epithelialization and controlling scar formation. Owing to the unique structure of HA incorporating and coating in VP-loaded PLA nanoparticles, HA/VP-PLA could be topically applied on wound to achieve targeted delivery to fibroblasts. Then, HA/VP-PLA released HA and lactic acid (LA) to stimulate the proliferation and migration of fibroblasts, as well as VP to inhibit Yes-associated protein (YAP) expression and nuclear localization to suppress fibrosis. In vitro (skin fibroblasts) and in vivo (rat and rabbit models) experiments strongly suggested that HA/VP-PLA promoted scarless wound healing by accelerating wound re-epithelialization and controlling scar formation. Therefore, our work provides a feasible strategy for scarless wound healing, and the sophisticated HA/VP-PLA exhibit a great potential for clinical applications.

Keywords: Hyaluronic acid; Polylactic acid nanoparticles; Scarless wound healing; Verteporfin; Yes-associated protein.

MeSH terms

  • Animals
  • Cicatrix* / drug therapy
  • Cicatrix* / metabolism
  • Cicatrix* / prevention & control
  • Hyaluronic Acid* / chemistry
  • Nanogels
  • Polyesters
  • Rabbits
  • Rats
  • Re-Epithelialization
  • Skin / metabolism
  • Verteporfin
  • Wound Healing

Substances

  • Hyaluronic Acid
  • poly(lactide)
  • Nanogels
  • Verteporfin
  • Polyesters