Pluripotent polysaccharide coordinated hydrogels remodel inflammation, neovascularization and reepithelization for efficient diabetic wound prohealing

Chronic diabetic wounds seriously threaten the health and life of human beings, however, it is challenging to develop pluripotent dressings that comprehensively remodel inflammation microenvironment, neovascularization and reepithelization to achieve high performance healing in diabetic wounds. Herein we construct a bioinspired polysaccharide coordinated hydrogel composed of bisphosphate-modified β-glucan (BG) with bioactive metal ions of Zn²⁺ and Mg²⁺, in which multiple chelation enables fast gelation, self-healing, and dynamically sealing wounds. In vitro Mg²⁺ release from BGM or BGMZ could promote intracellular uptake of Zn²⁺ through upregulating Zn²⁺-related transporter protein ZIP6 while intracellular Mg²⁺ remained relatively stable via downregulating the Mg²⁺ transporter protein of MagT1. The screened lead hydrogel BGMZ could substantially polarize proinflammatory M1 to prohealing M2 phenotypes by the main BG-downregulating NF-kB signaling pathway, and both Mg²⁺ and Zn²⁺ release from BGMZ synergistically promoted proliferation and angiogenesis by upregulating PI3K/Akt signaling pathway, facilitating the reepithelization and tissue remodeling. Remarkably, single BGMZ treatment performed full-thickness wound closure, fast granulation and dermis regeneration, optimal neovascularization and reepithelization, high levels of overall collagen and fibrous collagen-I, and dense hair follicles, thus achieving high performance prohealing in diabetic wounds. Consequently, this study opens a new avenue to design pluripotent polysaccharide hydrogel dressing for structures and functions remodeling of chronic and diabetic wounds.