In Situ Sprayed Hydrogel Delivers Extracellular Vesicles Derived from Human Endometrial Organoids for Uterine Function Preservation and Fertility Restoration.
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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引用次数: 0
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.
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.