In Situ Sprayed Hydrogel Delivers Extracellular Vesicles Derived from Human Endometrial Organoids for Uterine Function Preservation and Fertility Restoration.

IF 10 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Xunsi Qin, Kai-Lun Hu, Qi Li, Yuze Sun, Tianliu Peng, Xiyao Liu, Jizhou Li, Wenhui Nan, Yang Yu, Xiangbing Qi, Rong Li
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Abstract

Impaired endometrial function and reduced receptivity remain significant causes of female infertility. Here, a sprayable hydrogel combined with human endometrial organoid extracellular vesicles (HEO-EVs) is developed to enhance uterine function preservation and fertility restoration. The peptide amphiphile hydrogel (labeled CPA) is engineered by conjugating a collagen-binding peptide with glutathione to impart its biocompatible adhesive and antioxidant properties. The therapeutic EVs are isolated and purified from human endometrial organoids that have been stably passaged long-term using a bioreactor-culture system. The resulting HEO-EVs-loaded CPA (CPA@HEO-EVs) rapid gelation, triggered by salt-ion interactions, occurs when the fluid is sprayed onto the uterine lining. The ex vivo studies demonstrate that CPA@HEO-EVs promote cell proliferation, scavenges free radicals, and increases tube formation in human umbilical vein endothelial cells. In vivo experiments further validate that in situ spraying with the CPA@HEO-EVs can promote neovascularization, prevent localized endometrial fibrosis, and effectively enhance fertility in a mouse model of endometrial injury. These findings highlight the promising clinical application of in situ sprayed CPA@HEO-EVs hydrogel for targeted endometrial therapy.

原位喷涂水凝胶可输送从人类子宫内膜器官组织中提取的细胞外囊泡,用于保留子宫功能和恢复生育能力。
子宫内膜功能受损和接受能力下降仍然是导致女性不孕的重要原因。在这里,我们开发了一种与人类子宫内膜类细胞外囊泡(HEO-EVs)相结合的可喷涂水凝胶,以增强子宫功能的保护和生育能力的恢复。肽双亲水凝胶(标记为 CPA)是通过将胶原结合肽与谷胱甘肽共轭来赋予其生物相容性的粘附性和抗氧化性。治疗性 EV 是通过生物反应器培养系统从长期稳定传代的人类子宫内膜器官组织中分离和纯化的。当液体喷洒到子宫内膜上时,由盐离子相互作用引发的HEO-EVs负载CPA(CPA@HEO-EVs)迅速凝胶化。体内外研究表明,CPA@HEO-EVs 能促进细胞增殖、清除自由基,并增加人脐静脉内皮细胞中输卵管的形成。体内实验进一步验证了原位喷洒 CPA@HEO-EVs 可促进血管新生,防止局部子宫内膜纤维化,并有效提高子宫内膜损伤小鼠模型的生育能力。这些发现凸显了原位喷涂 CPA@HEO-EVs 水凝胶用于子宫内膜靶向治疗的临床应用前景。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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