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

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2025-05-12 Epub Date: 2025-04-25 DOI:10.1021/acs.biomac.5c00132

Xiaowei Zhang, Yongping Lu, Liqun Yang, Yu Sui, Chong Zhang, Wei Zhang, Jing Guo, Keke Wang, Xiaoliang Liu, Meina Lin

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引用次数: 0

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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用于siRNA递送的双相互作用超分子水凝胶系统在干细胞治疗中增强子宫内膜容受性。

子宫内膜容受性是胚胎着床成功的关键。干细胞疗法有望改善子宫内膜健康。我们开发了一种基于立体络合三嵌段共聚物（MPEG-(sc-PLA)- pei）和α-环糊精的超分子水凝胶支架，用于共递送经血来源的子宫内膜干细胞（MenSCs）和靶向DNA甲基转移酶1 （DNMT1）的siRNA，使rnai介导的基因沉默能够改善子宫内膜的接受性。所制得的α-CD/MPEG-(sc-PLA)- pei水凝胶具有较高的机械稳定性和良好的自愈能力，并通过主客体相互作用和立体络合的双重相互作用机制持续释放siRNA。体外研究表明，包裹在MPEG-(sc-PLA)- pei复合物内的DNMT1 siRNA具有优越的细胞摄取能力，导致子宫内膜容受性标志物（包括HOXA10、ITGB3和E-cadherin）显著上调。体内实验表明，装载DNMT1 sirna的水凝胶通过治疗性转基因在MenSCs中表达促进子宫内膜重塑。这些发现表明，这种多功能水凝胶系统可以作为干细胞治疗的有效工具，旨在增强子宫内膜容受性。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.