Photo-Cross-Linked and Photothermal Flammulina velutipes Polysaccharide Hydrogel Loaded with Caffeic Acid-Copper Nanozyme for Diabetic Wound Healing.

Diabetic ulcers remain a persistent global health challenge. Developing therapeutic systems with antibacterial, antioxidant, anti-inflammatory, and pro-angiogenic properties presents a promising strategy for effectively and rapidly treating diabetic wounds and preventing the development of diabetic ulcers. Herein, a photo-cross-linked Flammulina velutipes polysaccharide (FVP) containing double bonds was obtained through extraction and purification of FVP, and a facile reaction using methacrylic anhydride. The FVP was further combined with caffeic acid-copper nanozyme (CCN) to fabricate a series of multifunctional photo-cross-linked hydrogels (FVP@CCN) for diabetic wound healing. The FVP@CCN demonstrated rapid degradability, tunable mechanical properties, considerable intrinsic antimicrobial activity, and excellent biocompatibility. Additionally, the incorporated CCN, possessing peroxidase-like nanozyme activity, further endowed FVP@CCN with strong photothermal-induced antimicrobial ability, reactive oxygen species (ROS) scavenging capability, angiogenesis promotion activities, and pH-responsive release of CA and Cu2+. In vivo studies confirmed that FVP@CCN provided synergistic treatment against multiple healing impairments associated with diabetic wounds, exhibiting hemostasis, sustainable antibacterial, antioxidant, anti-inflammatory, angiogenesis-promotion, cell-proliferation, and hair follicle-regeneration, ultimately resulting in a diabetic wound closure rate exceeding 90% within 7 days. The multifunctional FVP@CCN hydrogel holds significant potential for diabetic wound healing, and its fabrication strategy can be extended to other plant-based polysaccharide hydrogels.