2. Academic Validation
  3. A Dual-Interaction Supramolecular Hydrogel System for siRNA Delivery to Enhance Endometrial Receptivity in Stem Cell Therapy

A Dual-Interaction Supramolecular Hydrogel System for siRNA Delivery to Enhance Endometrial Receptivity in Stem Cell Therapy

  • Biomacromolecules. 2025 May 12;26(5):3044-3058. doi: 10.1021/acs.biomac.5c00132.
Xiaowei Zhang 1 2,  Yongping Lu 1 2,  Liqun Yang 3,  Yu Sui 1 2 4,  Chong Zhang 1 2,  Wei Zhang 1 2,  Jing Guo 1 2,  Keke Wang 5,  Xiaoliang Liu 1 2,  Meina Lin 1 2
Affiliations

Affiliations

  • 1 Shenyang Key Laboratory of Biomedical Polymers, Liaoning Institute of birth health and development, Reproductive Hospital of China Medical University, 10 Puhe street, Huanggu District, Shenyang, Liaoning 110031, China.
  • 2 NHC Key Laboratory of Reproductive Health and Medical Genetics, China Medical University, 77 Puhe Road, North New Area, Shenyang, Liaoning 110122, China.
  • 3 Research Center for Biomedical Materials, Shenyang Key Laboratory of Biomedical Polymers, Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, Liaoning 110004, China.
  • 4 Institute of Health Sciences, Key Laboratory of Medical Cell Biology of Ministry of Education, China Medical University, 77 Puhe Road, North New Area, Shenyang, Liaoning 110122, China.
  • 5 Department of Pharmacy, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning 110001, China.
PMID: 40279154 DOI: 10.1021/acs.biomac.5c00132
Abstract

Endometrial receptivity is crucial for embryo implantation success. Stem cell therapy shows promise for improving endometrial health. We developed a supramolecular hydrogel scaffold based on stereocomplexed triblock copolymers (MPEG-(sc-PLA)-PEI) and α-cyclodextrin for codelivering menstrual blood-derived endometrial stem cells (MenSCs) and siRNA targeting DNA methyl transferase 1 (DNMT1), enabling RNAi-mediated gene silencing to improve endometrial receptivity. The resulting α-CD/MPEG-(sc-PLA)-PEI hydrogels exhibited high mechanical stability, excellent self-healing capabilities, and sustained siRNA release via a dual-interaction mechanism involving host-guest interaction and stereocomplexation. In vitro studies indicated superior cellular uptake of DNMT1 siRNA encapsulated within MPEG-(sc-PLA)-PEI complexes, resulting in significant upregulation of endometrial receptivity markers, including HOXA10, ITGB3, and E-cadherin. In vivo experiments showed that DNMT1 siRNA-loaded hydrogels facilitated endometrial remodeling through therapeutic transgene expression in MenSCs. These findings suggest that this multifunctional hydrogel system may serve as an effective tool for stem cell-based therapies aimed at enhancing endometrial receptivity.

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