Metal–Polyphenol Nanoparticles-Loaded Ferulic Acid-Functionalized Herbal Polysaccharide Hydrogel with Enhanced Antioxidant and Proangiogenic Functions for Accelerated Infected Wound Healing

Abstract

Natural polysaccharide-based bioactive materials have demonstrated great potential in wound healing, yet their further development as functional hydrogel wound dressings remains challenged by conventional crosslinking strategies and material design. Inspired by the photosensitivity of cinnamic acid derivatives from their unique structures, we proposed and validated the bioactive small molecule ferulic acid (FA) as a photopolymerizable agent for natural polysaccharides. Bletilla striata polysaccharide (BSP), a well-characterized wound-dressing polysaccharide, was functionalized with FA to form a photocurable hydrogel (BSP-FA) under 405 nm UV irradiation; silk fibroin (SF) was integrated to enhance mechanical properties, and the metal-phenolic nanoparticles (SalB–Ga) were loaded into the hydrogel to endow it with enhanced antioxidant and pro-angiogenic activities. The hydrogel exhibited good mechanical performance, biocompatibility, and anti-inflammatory activity, inhibiting macrophage M1 polarization, accelerating wound closure, promoting angiogenesis/collagen deposition, and alleviating inflammation in rat models, while significantly enhancing wound healing and tissue remodeling in infected pig models. Collectively, we developed an FA-mediated photocrosslinking strategy applicable to natural polysaccharide hydrogels, demonstrating its therapeutic potential in large animal models and providing a promising sustainable strategy for advanced photocrosslinkable hydrogel dressings.