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

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier Science Publishers, 1984-
    • Subject Terms:
      Hydrogels*/administration & dosage ; Wound Healing*/drug effects ; Zinc*/administration & dosage ; Inflammation*/drug therapy ; Neovascularization, Physiologic*/drug effects ; Magnesium*/administration & dosage; Animals ; Male ; beta-Glucans/chemistry ; beta-Glucans/pharmacology ; Mice ; Humans ; Diabetes Mellitus, Experimental ; Mice, Inbred C57BL ; Polysaccharides/chemistry
    • Abstract:
      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 Zn 2+ and Mg 2+ , in which multiple chelation enables fast gelation, self-healing, and dynamically sealing wounds. In vitro Mg 2+ release from BGM or BGMZ could promote intracellular uptake of Zn 2+ through upregulating Zn 2+ -related transporter protein ZIP6 while intracellular Mg 2+ remained relatively stable via downregulating the Mg 2+ 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 Mg 2+ and Zn 2+ 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.
      Competing Interests: Declaration of competing interest These authors declare no competing financial interest.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Chronic wound dressing; Comprehensive treatment; Inflammation microenvironment; Polymeric hydrogel; Structures and functions remodeling
    • Accession Number:
      0 (Hydrogels)
      J41CSQ7QDS (Zinc)
      I38ZP9992A (Magnesium)
      0 (beta-Glucans)
      0 (Polysaccharides)
    • Publication Date:
      Date Created: 20241116 Date Completed: 20241221 Latest Revision: 20241222
    • Publication Date:
      20241223
    • Accession Number:
      10.1016/j.jconrel.2024.11.027
    • Accession Number:
      39549729