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形状记忆支架靶向炎症与纤维化以修复宫腔粘连子宫内膜并恢复生育力

Shape-memory scaffold targets inflammation and fibrosis to restore endometrium and fertility in intrauterine adhesions

PubMed · 辅助生殖临床 · Sci Adv 大子刊 IF 11.7 · 文献 · 2026-11-06
Yang K, Wu H, Ma T, Zhang Y, Liu J, Chen Y, Liu M, Wu Q, Yang S, Wang Y 等 14 人
DOI 10.1126/sciadv.aee4682 · PMID 42993828 · 原文链接 ↗ · Scholar
综合 92.0 模型 84.0 · deepseek/deepseek-flash · 强度 low 已入选 期刊加权 +8 子宫内膜与植入 辅助生殖技术与临床结局 多组学与方法学 生殖内分泌
新颖 88严谨 82影响 84领域相关 90转化 83

摘要

该研究针对宫腔粘连(IUA)导致的不孕,开发可微创植入、顺序释药并具屏障保护作用的双药双功能可降解形状记忆再生支架(BiSMR)。基于化学、机械及联合损伤模型的蛋白质组学分析,作者将表没食子儿茶素没食子酸酯(EGCG)与17β-雌二醇(E2)联用,构建E2负载PLTG骨架与PDA-EGCG@HAMA涂层,实现EGCG快速释放后E2持续释放。体外实验显示其促进增殖、迁移、血管生成及M2极化并抑制肌成纤维细胞转化;大鼠IUA模型中恢复内膜结构与血管化、减少纤维化,并改善着床与活产率。

原文摘要

Intrauterine adhesion (IUA) is a major cause of infertility, yet current treatments remain limited in preventing fibrosis and restoring functional endometrium. We report a bi-drug, bifunctional, biodegradable shape-memory regenerative (BiSMR) scaffold enabling minimally invasive implantation, sequential drug release, and barrier protection. Proteomic profiling of chemical, mechanical, and combined injury models revealed inflammatory activation, extracellular matrix remodeling, and impaired regenerative programs, providing a molecular rationale for combining epigallocatechin gallate (EGCG) with 17β-estradiol (E2). BiSMR couples an E2-loaded PLTG [poly(l-lactide)-co-trimethylene carbonate-co-glycolic acid] backbone with a PDA-EGCG@HAMA coating, enabling rapid EGCG release followed by sustained E2 delivery. In vitro, BiSMR promoted cell proliferation, migration, angiogenesis, and M2 polarization while suppressing myofibroblast transition. In rat IUA models, BiSMR restored endometrial structure and vascularization, reduced fibrosis, and improved implantation and live birth rates. Proteomics revealed down-regulation of fibrosis- and inflammation-related effectors and restoration of protein biosynthesis and regenerative pathways. BiSMR offers a promising strategy for IUA therapy and fertility restoration.

推荐理由:该研究将多组学损伤分型与双药时序释放支架结合,在动物模型中同时改善子宫内膜结构与生育结局,为宫腔粘连提供较有转化潜力的再生策略;但证据仍限于大鼠,临床获益需人体验证。

关键词:宫腔粘连 · 形状记忆支架 · 子宫内膜再生 · 炎症与纤维化 · 控释给药 · 生育力恢复

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条目 #37 · 入库 2026-11-08 11:43 · JSON · Journal Article