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Here, astragaloside IV (AS), known for its regulatory role in ferroptosis, was encapsulated in the cavity of apoferritin (HFn) after an in situ biomineralization process involving MnO2, resulting in the synthesis of HFn@MnO2\/AS nanoparticles. These nanoparticles were then dispersed in chitosan\/polyvinyl alcohol\/glutaraldehyde\/sodium \u03b2-glycerophosphate (CGPG) hydrogels to form CGPG-HFn@MnO2\/AS injectable thermosensitive hydrogels that can scavenge reactive oxygen species (ROS) in the microenvironment. Our findings indicated that the prepared CGPG-HFn@MnO2\/AS hydrogel exhibited remarkable efficacy in scavenging ROS in vitro, effectively ameliorating the oxidative stress microenvironment post-SCI. Furthermore, it inhibited oxidative stress-induced ferroptosis in vitro and in vivo by regulating SIRT1 signaling, thereby promoting neuronal cell migration and repair. Hence, the developed hydrogel combining MnO2 and AS exhibited multifaceted abilities to modulate the pathological microenvironment, providing a promising therapeutic strategy for central nervous system (CNS) diseases.<\/jats:p>","DOI":"10.3390\/pharmaceutics16081057","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T05:19:38Z","timestamp":1723439978000},"page":"1057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Biomineralized MnO2 Nanoparticle-Constituted Hydrogels Promote Spinal Cord Injury Repair by Modulating Redox Microenvironment and Inhibiting Ferroptosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Yuyu","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, 899 Pinghai Rd, Suzhou 215031, China"},{"name":"Department of Orthopedic, Nantong Third People\u2019s Hospital of Nantong University and Affiliated Nantong Hospital 3 of Nantong University, 60 Qingnian Rd, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, 899 Pinghai Rd, Suzhou 215031, China"},{"name":"Department of Spine Surgery, Nantong City No.1 People\u2019s Hospital and The Affiliated Hospital 2 of Nantong University, 666 Shengli Rd, Nantong 226014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, 899 Pinghai Rd, Suzhou 215031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9058-2643","authenticated-orcid":false,"given":"Tianqing","family":"Liu","sequence":"additional","affiliation":[{"name":"NICM Health Research Institute, Western Sydney University, Westmead, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, 899 Pinghai Rd, Suzhou 215031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114570","DOI":"10.1016\/j.expneurol.2023.114570","article-title":"The dual role of microglia in neuropathic pain after spinal cord injury: Detrimental and protective effects","volume":"370","author":"Sun","year":"2023","journal-title":"Exp. 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