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<p>Intrauterine adhesions (IUA), a leading cause of female infertility, result from a pathological switch in the uterine injury response from regeneration to fibrotic scarring. Current treatments are often inadequate as they fail to address this fundamental shift. Here, we report a “decidualization-empowered” hydrogel that reverses this pathology by synergistically combining a bioactive extracellular matrix from decidualized endometrium (DEndo-UdECM) with the sustained release of the anti-fibrotic peptide Thymosin β4 (Tβ4). In a murine IUA model, a single administration of the hydrogel restores endometrial architecture, resolves fibrosis, and, most critically, leads to a near-complete recovery of fertility. Mechanistically, the hydrogel orchestrates a pro-regenerative niche by reprogramming macrophages to an M2 phenotype while dually inhibiting pyroptosis-driven inflammation and the canonical TGF-β/Smad3 fibrotic cascade. Together, these findings demonstrate that mimicking the biological intelligence of a physiological niche can resolve complex fibrotic diseases and restore organ function.</p>

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Decidualization-empowered ECM hydrogel integrating sustained Tβ4 release drives endometrial regeneration in intrauterine adhesions

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月21日

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  • Yuxiang Liang,
  • Zhaowei Yu,
  • Shaobo Du,
  • Yuqian Guo,
  • Jing Li,
  • Yujia Yan,
  • Shanshan Jin,
  • Wenjing Liang,
  • Mengyuan Li,
  • Ning Jin,
  • Jiao Yang,
  • Zhiwei Peng,
  • Zhaoyang Chen,
  • Hailan Yang,
  • Zhizhen Liu,
  • Qizhi Shuai,
  • Liping Li,
  • Jun Xie

摘要

Intrauterine adhesions (IUA), a leading cause of female infertility, result from a pathological switch in the uterine injury response from regeneration to fibrotic scarring. Current treatments are often inadequate as they fail to address this fundamental shift. Here, we report a “decidualization-empowered” hydrogel that reverses this pathology by synergistically combining a bioactive extracellular matrix from decidualized endometrium (DEndo-UdECM) with the sustained release of the anti-fibrotic peptide Thymosin β4 (Tβ4). In a murine IUA model, a single administration of the hydrogel restores endometrial architecture, resolves fibrosis, and, most critically, leads to a near-complete recovery of fertility. Mechanistically, the hydrogel orchestrates a pro-regenerative niche by reprogramming macrophages to an M2 phenotype while dually inhibiting pyroptosis-driven inflammation and the canonical TGF-β/Smad3 fibrotic cascade. Together, these findings demonstrate that mimicking the biological intelligence of a physiological niche can resolve complex fibrotic diseases and restore organ function.