Xiangyu Liu , Biao Ma , Sihan Hu , Dandan Li , Chun Pan , Zhuobin Xu , Hao Chen , Yongxiang Wang , Huihui Wang
{"title":"Phase-adapted metal ion supply for spinal cord repair with a Mg–Zn incorporated chimeric microsphere","authors":"Xiangyu Liu , Biao Ma , Sihan Hu , Dandan Li , Chun Pan , Zhuobin Xu , Hao Chen , Yongxiang Wang , Huihui Wang","doi":"10.1016/j.biomaterials.2025.123253","DOIUrl":null,"url":null,"abstract":"<div><div>Dynamic alterations in metal ion concentrations are observed in the pathological process of spinal cord injury (SCI). Hence, strategically supplying metal ions in a phase-adapted manner is promising to facilitate injured spinal cord repair by preventing pathological damage. To achieve this, a chimeric hydrogel microsphere with Mg<sup>2+</sup>-crosslinked methacrylate gelatin as the \"shell\" and Zn<sup>2+</sup>-loaded poly (lactic-co-glycolic acid) (PLGA) as the \"core\" was designed. The chimeric microspheres allow continuous delivery of Mg<sup>2+</sup> or Zn<sup>2+</sup> at the exact required phase in SCI pathological process. Early release of Mg<sup>2+</sup> reduced inflammation by diminishing the secretion of proinflammatory cytokines due to changes in macrophage polarization, which further suppressed scar formation to create an ideal space for neural regeneration. The subsequently released Zn<sup>2+</sup> at the late phase effectively promoted neural cell proliferation and regeneration, which was accompanied by activation of mature neurons, interneurons, and motor neurons, leading to significant behavioral recovery. Thus, this study underscores the critical role of metal ions at different phases of injured spinal cord repair and describes the construction of an injectable chimeric hydrogel microsphere carrying distinct metal ions with a core-shell structure. Chimeric microspheres overcome the discrepancy between the inflammatory response and neural regeneration and are a promising therapeutic strategy for injured spinal cord repair.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123253"},"PeriodicalIF":12.8000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0142961225001723","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Dynamic alterations in metal ion concentrations are observed in the pathological process of spinal cord injury (SCI). Hence, strategically supplying metal ions in a phase-adapted manner is promising to facilitate injured spinal cord repair by preventing pathological damage. To achieve this, a chimeric hydrogel microsphere with Mg2+-crosslinked methacrylate gelatin as the "shell" and Zn2+-loaded poly (lactic-co-glycolic acid) (PLGA) as the "core" was designed. The chimeric microspheres allow continuous delivery of Mg2+ or Zn2+ at the exact required phase in SCI pathological process. Early release of Mg2+ reduced inflammation by diminishing the secretion of proinflammatory cytokines due to changes in macrophage polarization, which further suppressed scar formation to create an ideal space for neural regeneration. The subsequently released Zn2+ at the late phase effectively promoted neural cell proliferation and regeneration, which was accompanied by activation of mature neurons, interneurons, and motor neurons, leading to significant behavioral recovery. Thus, this study underscores the critical role of metal ions at different phases of injured spinal cord repair and describes the construction of an injectable chimeric hydrogel microsphere carrying distinct metal ions with a core-shell structure. Chimeric microspheres overcome the discrepancy between the inflammatory response and neural regeneration and are a promising therapeutic strategy for injured spinal cord repair.
期刊介绍:
Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.