A Multifunctional Biomimetic Hydrogel with Antibacterial and Antifibrotic Properties for Scar Minimizing Repair of Infected Skin Wounds.

Authors

Shiyu Liang, Zhongwu Bei, Jianan Li, Xiaorui Yu, Qi Tong, Jie Chen, Zhiyong Qian

Published in

Acta biomaterialia. Oct 27, 2026. Epub Oct 27, 2026.

Abstract

Infected wounds are characterized by persistent bacterial colonization, which exacerbates inflammation, interferes with extracellular matrix remodeling, and ultimately leads to hypertrophic scarring. Conventional wound dressings offer limited antibacterial durability, immune regulation, and regenerative support, thereby restricting their ability to prevent fibrosis. In this study, we engineered a biomimetic dual-crosslinked network hydrogel (GH-L-VP@PDA) constructed from phenylboronic-acid-modified gelatin methacrylate (GelMA-PBA) and thiolated hyaluronic acid (HA-SH), incorporating the antimicrobial peptide LL-37 and verteporfin-loaded polydopamine nanoparticles (VP@PDA). By integrating LL-37 and VP@PDA nanoparticles, the hydrogel enables coordinated therapy, providing early antibacterial protection and sustained regulation of Yes-associated protein (YAP)-mediated fibrotic remodeling. Consequently, the hydrogel simultaneously regulates infection, inflammation, and fibrotic remodeling, promoting regenerative healing while attenuating excessive fibrosis. Furthermore, benchmarking against commercially available wound dressings demonstrated the favorable therapeutic performance of GH-L-VP@PDA in infected wound treatment. This work presents an intelligent-network therapeutic platform that targets infection-associated fibrosis through YAP-mediated remodeling, providing a strategy for infected wound repair with attenuated fibrotic remodeling. STATEMENT OF SIGNIFICANCE: Infected wound healing remains challenging due to the interplay among bacterial infection, persistent inflammation, and excessive fibrosis. Here, we developed a biomimetic dual-crosslinked hydrogel composed of phenylboronic acid-modified gelatin methacrylate, thiolated hyaluronic acid, LL-37, and verteporfin-loaded polydopamine nanoparticles. The hydrogel integrates antibacterial, immunomodulatory, and antifibrotic properties, with the latter associated with YAP regulation. In vitro and in vivo studies demonstrated its potential to control infection, modulate inflammation, promote angiogenesis, and improve collagen remodeling and tissue regeneration. Comparisons with commercial wound dressings further supported its therapeutic potential. This study provides a multifunctional hydrogel strategy for coordinated regulation of infected wound healing.

PMID:
42946320
Bibliographic data and abstract were imported from PubMed on 28 Oct 2026.

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