Photocrosslinkable Chitosan Quaternary Ammonium Salt-Based Ternary Hydrogel with Fibroblast Growth Factor 21 for Diabetic Wound Healing

TL;DR

A new hydrogel combining chitosan, gelatin, and collagen with FGF-21 was developed to improve diabetic wound healing by reducing inflammation and promoting tissue repair.

Contribution

A novel ternary hydrogel with FGF-21 and antimicrobial properties was developed for diabetic wound healing.

Findings

The hydrogel promoted anti-inflammatory macrophage polarization and fibroblast activity in vitro.

In diabetic mice, the hydrogel accelerated wound closure and improved reepithelialization and angiogenesis.

The composite material synergizes inflammation resolution, antimicrobial action, and mechanical support.

Abstract

Diabetic wounds represent a critical public health challenge due to impaired healing processes driven by chronic inflammation, infection, and biomechanical deficiencies. Despite advances in wound dressings and negative-pressure therapy, current treatments often fail to provide sufficient mechanical support or to fully resolve inflammatory responses, resulting in prolonged ulceration and high risk of complications. To address these limitations, a photocrosslinkable chitosan quaternary ammonium salt (CQS) derivative (methacrylated CQS [CQS-MA]) was developed to accelerate gelation and improve structural integrity. We then used ultraviolet-initiated copolymerization of CQS-MA with gelatin methacrylate (GelMA) and type I collagen to fabricate a ternary composite hydrogel encapsulating fibroblast growth factor 21 (FGF-21), termed G/C-CS@FGF-21. This composite hydrogel synergistically combined FGF-21’s early-stage inflammation-resolving activity, CQS’s sustained antimicrobial function, GelMA’s tunable mechanical resilience, and collagen’s native cell-adhesive ligands, which could promote all phases of wound repair. In vitro, G/C-CS@FGF-21 promoted macrophage polarization toward the anti-inflammatory M2 phenotype and enhanced fibroblast proliferation and migration. In a full-thickness diabetic mouse wound-healing model, treatment with G/C-CS@FGF-21 accelerated wound closure by mitigating inflammation and promoting reepithelialization and angiogenesis. These findings suggest that the G/C-CS@FGF-21 hydrogel holds strong potential for future clinical translation in diabetic wound management.

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