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Bioinspired glycosaminoglycan hydrogels via click chemistry for 3D dynamic cell encapsulation

机译:通过咔哒化化学进行3D动态细胞封装,生物悬浮的糖甘油蛋聚糖水凝胶

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摘要

Cell encapsulation within 3D hydrogels is an attractive approach to develop effective cell-based therapies. However, little is known about how cells respond to the dynamic microenvironment resulting from hydrogel gelation-based cell encapsulation. Here, a tunable biomimetic hydrogel system that possesses alterable gelation kinetics and biologically relevant matrix stiffness is developed to study 3D dynamic cellular responses during encapsulation. Hydrogels are synthesized by crosslinking thiolated hyaluronic acid and thiolated chondroitin sulfate with poly(ethylene glycol) diacrylate under cell-compatible conditions. Hydrogel properties are tailored by altering thiol substitution degrees of glycosaminoglycans or molecular weights of crosslinkers. Encapsulation of human mesenchymal stem cells through hydrogel gelation reveals high cell viability as well as a three-stage gelation-dependent cellular response in real-time focal adhesion kinase (FAK) phosphorylation in live single cells. Furthermore, stiffer hydrogels result in higher equilibrium FAK activity and enhanced actin protrusions. Our results demonstrate the promise of hydrogel-mediated cellular responses during cell encapsulation. (c) 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47212.
机译:三维水凝胶内的细胞封装是开发有效的基于细胞的疗法有吸引力的方法。然而,知之甚少细胞从水凝胶基于凝胶化细胞封装产生的动态的微环境如何响应。这里,拥有可变凝胶动力学和生物相关矩阵刚度可调仿生水凝胶系统的开发封装过程中,研究三维动态细胞反应。通过交联被合成水凝胶硫醇化细胞相容的条件下的透明质酸和硫醇化硫酸软骨素与聚(乙二醇)二丙烯酸酯。水凝胶性质通过改变硫醇取代度糖胺聚糖或交联剂的分子量的调整。人类的封装间质干细胞通过水凝胶的凝胶化揭示了高的细胞存活率,以及在实时的粘着斑激酶(FAK)磷酸化作用在活的单细胞的三阶段凝胶化依赖性细胞反应。此外,水凝胶更硬导致更高的平衡FAK活性和增强的肌动蛋白的突起。我们的研究结果表明水凝胶介导的细胞反应的细胞封装时的承诺。 (c)2018 Wiley期刊,Inc.J.Phill。聚合物。 SCI。 2019年,136,47212。

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