Photo-Cross-Linked and Photothermal <i>Flammulina velutipes</i> Polysaccharide Hydrogel Loaded with Caffeic Acid-Copper Nanozyme for Diabetic Wound Healing
Meimei Fu, Qianru Xiang, Zhuoyi Huang, Wenjun Luo, Zhou Fang, Jintao Li, Yue Li, Zijun Xia, Yina Huang, Yitao Zhao, Wenzhen Liao, Jinshan Guo
Abstract
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 Cu 2+ . 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.