Decidualization-empowered ECM hydrogel integrating sustained Tβ4 release drives endometrial regeneration in intrauterine adhesions
- 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
2026-01-21
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.