Ru single-atom nanozymes targeting ROS-ferroptosis pathways for enhanced endometrial regeneration in intrauterine adhesion therapy

IF 12.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL
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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.
针对 ROS-ferroptosis 通路的 Ru 单原子纳米酶,在宫内粘连治疗中促进子宫内膜再生。
宫腔内粘连(IUA)是妇科领域的一项重大挑战,其特点是过度纤维化和生殖功能受损,导致严重不孕。虽然与干细胞结合的生物相容性水凝胶为IUA治疗提供了一种前景广阔的方法,但临床应用仍然有限。最近的研究强调了铁突变和活性氧(ROS)在IUA发病机制中的作用,但通过抗氧化应激靶向铁突变的策略尚未得到充分探索。本研究探讨了加入壳聚糖水凝胶的 Ru-单原子纳米酶(Ru-SAN)治疗 IUA 的疗效和机制。Ru-SAN 可模拟过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的酶活性,能有效清除过量的 ROS,有望治疗氧化应激诱发的疾病。研究结果表明,Ru-SAN 具有卓越的抗氧化能力,能显著抑制损伤部位的 ROS-ferroptosis 循环。这通过抑制炎症、加强间质到上皮的转化、促进血管生成和极化 M2 巨噬细胞,为损伤后的修复创造了有利的微环境。重要的是,它能减轻炎症和胶原纤维过度沉积造成的不良修复结果,最终恢复子宫腺体结构和厚度,从而实现恢复生育能力和活产率的最终目标。总之,我们的研究描述了一种开创性的治疗方法,利用 Ru-SAN 的抗氧化特性来靶向铁蛋白沉积,从而为 IUA 提供了一种有效的治疗方法。
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来源期刊
Biomaterials
Biomaterials 工程技术-材料科学:生物材料
CiteScore
26.00
自引率
2.90%
发文量
565
审稿时长
46 days
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.
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