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Mater. Today Bio, Jun 2026, 38 103235 | https://doi.org/10.1016/j.mtbio.2026.103235 A sequential and synergistic release sacrificial microgels scaffold for endometrial niche reprogramming and fertility restoration

Qian Liu ^a,b,c,1, Shun Lu ^d,1, Junhua Zhou ^b,1, Jie Xu ^e, Jiaqin Shao ^b, Jianqiong Zheng ^h, Yinhe Zhang ^b, Anqi Ye ^e, Shuhong Tian^f, Chuanqi Qiu^a, Mengqi Jin ^b, Maolin Qin ^b, Zichang Wu ^b, Somy Yoon ^c, Ling Xie ^b,g, Lei Chen ^a,b, Jian Xiao^a,b

^aDepartment of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
^bSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
^cCollege of Pharmacy, Chonnam National University, Gwangju, 61186, South Korea
^dDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315020, China
^eOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
^fHainan Pharmaceutical Research and Development Science Park, Hainan Medical University, Haikou, 571199, China
^gCixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, Zhejiang, 315399, China
^hDepartment of Obstetrics and Gynecology, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou Maternal and Child Health Care Hospital, Wenzhou, Zhejiang, 325035, China

¹Q. Liu, S. Lu and J. Zhou contributed equally to this work.
Corresponding authors: Somy Yoon, Ling Xie, Lei Chen, Jian Xiao

Abstract

Intrauterine adhesions (IUA) remain a therapeutic challenge, necessitating advanced regenerative strategies. Herein, we propose a "programmed endometrial niche" strategy, a 3D-printed adipose-derived stem cells (ADSCs) hydrogel scaffold is constructed via microfluidic technology, incorporating platelet-rich plasma (PRP)-loaded thermosensitive gelatin microgels (PMS@AH) for sequential and synergistic delivery of PRP and ADSCs to restore the endometrial immune microenvironment and niche. In vitro assays demonstrate that PMS@AH possesses excellent biocompatibility and significantly promoted cell proliferation, migration, and angiogenesis, accompanied by potent anti-inflammatory activity. In both rat and cynomolgus macaque IUA models, it effectively restored endometrial structure, reduced fibrosis and inflammation, and successfully restored fertility. Mechanistically, RNA-sequencing analysis reveals that PMS@AH involves suppressing the IL-17/nuclear factor-κB (NF-κB) pathway to modulate the immune microenvironment and inhibiting the Wnt/β-catenin pathway to program the endometrial niche. This sequentially releasing scaffold presents a promising platform for treating IUA and broader applications in reproductive medicine.

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