{"title":"Ru single-atom nanozymes targeting ROS-ferroptosis pathways for enhanced endometrial regeneration in intrauterine adhesion therapy","authors":"","doi":"10.1016/j.biomaterials.2024.122923","DOIUrl":null,"url":null,"abstract":"<div><div>Intrauterine adhesion (IUA) presents a significant challenge in gynecology, characterized by excessive fibrosis and compromised reproductive function, leading to severe infertility. Although biocompatible hydrogels integrated with stem cells offer a promising approach for IUA therapy, clinical applications remain limited. Recent studies have highlighted the role of ferroptosis and reactive oxygen species (ROS) in IUA pathogenesis, yet strategies targeting ferroptosis through antioxidant stress are underexplored. This study investigates the therapeutic effects and mechanisms of a Ru-Single-Atom Nanozyme (Ru-SAN) incorporated into chitosan hydrogel for treating IUA. Ru-SAN, which mimics the enzyme activities of catalase, superoxide dismutase, and glutathione peroxidase, effectively clears excess ROS and shows promise in treating oxidative stress-induced diseases. The results demonstrate the superior antioxidative capabilities of Ru-SAN, significantly suppressing the ROS-ferroptosis cycle at the injury site. This creates a favorable microenvironment for post-injury repair by inhibiting inflammation, enhancing mesenchymal-to-epithelial transformation, promoting angiogenesis, and polarizing M2 macrophages. Importantly, it mitigates adverse repair outcomes from inflammation and excessive collagen fiber deposition, ultimately restoring uterine glandular structures and thickness, thereby achieving the ultimate goal of restoring fertility and live birth rates. In conclusion, our study delineates a pioneering therapeutic approach leveraging the antioxidant properties of Ru-SAN to target ferroptosis, thereby offering an efficacious treatment for IUA.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":12.8000,"publicationDate":"2024-10-30","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/S0142961224004575","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
Intrauterine adhesion (IUA) presents a significant challenge in gynecology, characterized by excessive fibrosis and compromised reproductive function, leading to severe infertility. Although biocompatible hydrogels integrated with stem cells offer a promising approach for IUA therapy, clinical applications remain limited. Recent studies have highlighted the role of ferroptosis and reactive oxygen species (ROS) in IUA pathogenesis, yet strategies targeting ferroptosis through antioxidant stress are underexplored. This study investigates the therapeutic effects and mechanisms of a Ru-Single-Atom Nanozyme (Ru-SAN) incorporated into chitosan hydrogel for treating IUA. Ru-SAN, which mimics the enzyme activities of catalase, superoxide dismutase, and glutathione peroxidase, effectively clears excess ROS and shows promise in treating oxidative stress-induced diseases. The results demonstrate the superior antioxidative capabilities of Ru-SAN, significantly suppressing the ROS-ferroptosis cycle at the injury site. This creates a favorable microenvironment for post-injury repair by inhibiting inflammation, enhancing mesenchymal-to-epithelial transformation, promoting angiogenesis, and polarizing M2 macrophages. Importantly, it mitigates adverse repair outcomes from inflammation and excessive collagen fiber deposition, ultimately restoring uterine glandular structures and thickness, thereby achieving the ultimate goal of restoring fertility and live birth rates. In conclusion, our study delineates a pioneering therapeutic approach leveraging the antioxidant properties of Ru-SAN to target ferroptosis, thereby offering an efficacious treatment for IUA.
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.