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.

中文翻译：

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多能多糖配位水凝胶重塑炎症、新生血管形成和再上皮化，以实现糖尿病伤口的高效促进愈合


慢性糖尿病伤口严重威胁着人类的健康和生命，然而，开发能够全面重塑炎症微环境、新生血管形成和再上皮化以实现糖尿病伤口高效愈合的多能敷料是一项挑战。在此，我们构建了一种生物启发多糖配位水凝胶，该水凝胶由二磷酸盐修饰的 β-葡聚糖 （BG） 和 Zn 2+ 和 Mg2+ 的生物活性金属离子组成，其中多重螯合可实现快速凝胶化、自愈和动态密封伤口。体外 BGM 或 BGMZ 释放的 Mg2+ 可通过上调 Zn2+ 相关转运蛋白 ZIP6 促进细胞内摄取 Zn2+，而细胞内 Mg2+ 通过下调 MagT1 的 Mg2+ 转运蛋白保持相对稳定。筛选的先导水凝胶 BGMZ 可通过主要 BG 下调 NF-kB 信号通路将促炎 M1 极化为促愈合 M2 表型，BGMZ 释放的 Mg2 + 和 Zn2 + 通过上调 PI3K/Akt 信号通路协同促进增殖和血管生成，促进再上皮化和组织重塑。值得注意的是，单一 BGMZ 治疗实现了全层伤口闭合、快速肉芽和真皮再生、最佳新生血管形成和再上皮化、高水平的整体胶原蛋白和纤维状胶原蛋白-I 以及致密的毛囊，从而在糖尿病伤口中实现了高性能的预愈合。因此，本研究为设计多能多糖水凝胶敷料开辟了一条新途径，用于慢性和糖尿病伤口的结构和功能重塑。