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通过二硫键交联的动态可光降解葡聚糖/明胶水凝胶微环境:促进干细胞生长与释放

Dynamic and photodegradable dextran/gelatin hydrogel niche crosslinked with disulfide bonds: Promoting growth and release of stem cells.

作者信息

Yu Qingyu, Hao Huizhong, Wang Weitong, Zhang Linhua, Huang Chenlu, Hao Jianying, Yang Xinyu, Zhu Dunwan, Li Junjie, Sun Hong

机构信息

School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, China; Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, China; Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300192, China.

Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, China.

出版信息

Int J Biol Macromol. 2025 Mar;293:139430. doi: 10.1016/j.ijbiomac.2024.139430. Epub 2024 Dec 31.

Abstract

Due to the utilization of well-defined artificial niches, stem cell culture in a three-dimensional hydrogel matrix has been a promising method for obtaining sufficient seed cells. Although various hydrogels can support desirable cell proliferation, establishing a normalized hydrogel that adequately mimics the extracellular matrix (ECM), maintains stemness and allows for controlled release of stem cells remains a significant challenge. Herein, we report a hydrogel composed of sulfobetaine-modified dextran and gelatin to maintain stemness and enable the rapid release of adipose-derived stem cells (ADSCs). Dextran can effectively maintain multipotent phenotype of ADSCs by grafting zwitterionic groups. Gelatin can significantly improve the proliferation of ADSCs. The hydrogel network they form effectively mimics the ECM microenvironment, providing an advantage when used as a three-dimensional niche to promote cell proliferation. Most importantly, the disulfide-crosslinked hydrogels show specific photodegradation capability, which precisely enables the system to achieve controlled release and efficient harvest of ADSCs. The cell viability (90 %) and harvest ratio (64 %) were well maintained by light degradation compared with GSH and collagenase degradation. Overall, this study offers a universal stem cell niche based on photodegradable hydrogel that shows great promise in the field of ADSCs proliferation and harvest.

摘要

由于使用了明确的人工微环境,在三维水凝胶基质中进行干细胞培养已成为获取足够种子细胞的一种有前景的方法。尽管各种水凝胶都能支持理想的细胞增殖,但建立一种能充分模拟细胞外基质(ECM)、维持干性并允许干细胞可控释放的标准化水凝胶仍然是一项重大挑战。在此,我们报道了一种由磺基甜菜碱修饰的葡聚糖和明胶组成的水凝胶,用于维持干性并实现脂肪来源干细胞(ADSCs)的快速释放。葡聚糖可以通过接枝两性离子基团有效地维持ADSCs的多能表型。明胶可以显著提高ADSCs的增殖。它们形成的水凝胶网络有效地模拟了ECM微环境,在用作促进细胞增殖的三维微环境时具有优势。最重要的是,二硫键交联的水凝胶具有特定的光降解能力,这使得该系统能够精确地实现ADSCs的可控释放和高效收获。与谷胱甘肽(GSH)和胶原酶降解相比,通过光降解能很好地维持细胞活力(90%)和收获率(64%)。总体而言,本研究提供了一种基于可光降解水凝胶的通用干细胞微环境,在ADSCs增殖和收获领域显示出巨大的潜力。

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