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Injectable Thermosensitive Hydrogel Containing Resveratrol-Laden Nanoparticles Promotes Hypertrophic Scar Repair in

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Summary

This study developed an injectable hydrogel loaded with resveratrol (Res) to improve hypertrophic scar treatment. The novel hydrogel enhances Res delivery, reduces scar size, and promotes healing by inhibiting autophagy and inducing apoptosis in fibroblasts.

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Dermatology

Background:

  • Resveratrol (Res) suppresses hypertrophic scars via autophagy inhibition, apoptosis induction, and oxidative stress reduction.
  • Poor bioavailability of Res limits its pharmaceutical application for scar treatment.

Purpose of the Study:

  • To develop an injectable, temperature-responsive hydrogel for enhanced delivery of Res (MSN@Res) for hypertrophic scar repair.
  • To evaluate the efficacy of the developed hydrogel in vitro and in vivo.

Main Methods:

  • Formulation of an injectable, temperature-responsive hydrogel using aldehyde-functionalized Pluronic F127 (FC) and adipic dihydrazide-modified hyaluronic acid (AHA).
  • Loading of Res into mesoporous silica nanoparticles (MSN@Res) for sustained release within the hydrogel.
  • In vitro cytotoxicity and biocompatibility assays with hypertrophic scar fibroblasts.
  • In vivo study on rat tail hypertrophic scars to assess scar size, thickness, and molecular markers.

Main Results:

  • The 8%FC/AHA-MSN@Res hydrogel demonstrated suitable porosity, mechanical strength, and sustained Res release.
  • In vitro tests showed minimal cytotoxicity, excellent biocompatibility, and significant antiproliferative activity against hypertrophic scar fibroblasts.
  • In vivo application significantly reduced scar size, epidermal and dermal thickness, suppressed oxidative stress, and modulated key molecular pathways (p38-MAPK, HIF-1α, p53, LC3-II, caspase-3).

Conclusions:

  • The developed composite hydrogel effectively inhibits autophagy and induces apoptosis in hypertrophic scar fibroblasts, leading to reduced cell viability and collagen deposition.
  • This injectable hydrogel system shows significant potential for clinical application in accelerating hypertrophic scar regression.