A WR3-NH2-loaded polysaccharide hydrogel with antibacterial, anti-inflammatory, and pro-healing properties for enhanced wound healing

TL;DR

A new hydrogel loaded with WR3-NH2 peptide shows antibacterial, anti-inflammatory, and healing properties to improve wound recovery.

Contribution

A multifunctional hydrogel combining WR3-NH2 with polysaccharides for enhanced wound healing is developed and tested.

Findings

SGHC-WR hydrogel accelerated wound closure and tissue regeneration in mice.

The hydrogel showed strong antibacterial activity against both Gram-positive and Gram-negative bacteria.

In vitro tests showed enhanced cell proliferation and reduced inflammation via MAPK pathway modulation.

Abstract

Wound healing is a complex process often compromised by infection, excessive inflammation, and impaired tissue regeneration. In this study, the antimicrobial peptide WR3-NH2 loaded multifunctional polysaccharide hydrogel (SGHC-WR) was developed. This hydrogel demonstrated favorable physicochemical properties, including porosity, injectability, degradability, and sustained release capability, while maintaining stability under storage conditions. In vitro studies indicated that WR3-NH2 significantly enhanced the proliferation and migration of HUVECs, HFF, and HaCaT cells, while also regulating cytokine secretion and modulating the MAPK signaling pathway to mitigate inflammation. SGHC-WR exhibited strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, including resistant strains, with low hemolysis rates and excellent cytocompatibility. In vivo evaluations using a full-thickness skin wound model in mice revealed that SGHC-WR accelerated wound closure, enhanced angiogenesis, promoted collagen deposition, and facilitated tissue remodeling. Histological analysis confirmed the regeneration of well-structured epidermis and hair follicles, while biosafety assessments showed no pathological damage in major organs and no dermal irritation following repeated application. Collectively, these findings demonstrate that SGHC-WR creates an optimized wound healing microenvironment by integrating antibacterial, anti-inflammatory, and regenerative functions. This work highlights SGHC-WR as a promising therapeutic biomaterial for advanced wound management and offers new insights into the synergistic application of antimicrobial peptides and polysaccharide hydrogels in regenerative medicine.

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•WR3-NH2 hydrogel offers a multifunctional platform for wound healing.•Integrates antibacterial, anti-inflammatory, and pro-regenerative effects.•Accelerates wound closure and enhances angiogenesis and tissue remodeling.•Demonstrates excellent biosafety and strong potential for clinical translation.

WR3-NH2 hydrogel offers a multifunctional platform for wound healing.

Integrates antibacterial, anti-inflammatory, and pro-regenerative effects.

Accelerates wound closure and enhances angiogenesis and tissue remodeling.

Demonstrates excellent biosafety and strong potential for clinical translation.

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