Promoting scarless wound closure utilizing an injectable thermosensitive hydrogel with anti-inflammatory, antioxidant, and scar formation inhibiting properties

Biomater Adv. 2025 Aug:173:214295. doi: 10.1016/j.bioadv.2025.214295. Epub 2025 Mar 25.

Abstract

Skin trauma, surgery, or burns can result in non-functional scar tissue, causing significant physiological and psychological harm to patients. Therefore, there is an urgent need for a treatment strategy that promotes rapid wound healing and suppresses scar formation. In this study, we developed a facile and injectable composite hydrogel system (PF-127@ERD) loaded with eriodictyol, which exhibits efficient sustained release of the scar-inhibiting compound at different stages of wound healing to facilitate rapid and scarless closure. Our findings revealed that PF-127@ERD not only stops bleeding and reduces local oxidative stress damage in skin wounds but also regulates the inflammatory microenvironment by inhibiting the expression of relevant inflammatory factors while promoting fibroblast migration. Furthermore, PF-127@ERD inhibits excessive collagen deposition and regulates the expression of genes associated with scar formation, thereby promoting scar-free wound healing. In a rat model of full-layer skin defects, skin wound tissue treated with PF-127@ERD healed faster, exhibited more orderly collagen alignment, and showed reduced scar tissue formation compared to other groups. This process may be due to its inhibition of ferroptosis-related pathways. Therefore, this straightforward hydrogel system based on the skin repair stage (PF-127@ERD) holds great potential for scarless wound healing.

Keywords: Anti-inflammation; Antioxidation; Eriodictyol (ERD); Ferroptosis; Scar; Wound healing.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / administration & dosage
  • Anti-Inflammatory Agents* / chemistry
  • Anti-Inflammatory Agents* / pharmacology
  • Anti-Inflammatory Agents* / therapeutic use
  • Antioxidants* / administration & dosage
  • Antioxidants* / chemistry
  • Antioxidants* / pharmacology
  • Antioxidants* / therapeutic use
  • Cicatrix* / drug therapy
  • Cicatrix* / pathology
  • Cicatrix* / prevention & control
  • Hydrogels* / administration & dosage
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Injections
  • Male
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Skin / drug effects
  • Skin / injuries
  • Skin / pathology
  • Wound Healing* / drug effects

Substances

  • Hydrogels
  • Antioxidants
  • Anti-Inflammatory Agents