Thiol-Methylsulfone based Hydrogels for 3D Cell Encapsulation.

Thiol-Methylsulfone based Hydrogels for 3D Cell Encapsulation.
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DOI:
10.1021/acsami.0c00709
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发表时间:
2020-01
影响因子:
9.5
通讯作者:
Julieta I. Paez;Aleeza Farrukh;Rocío Valbuena-Mendoza;M. Włodarczyk-Biegun;A. del Campo
Julieta I. Paez;Aleeza Farrukh;Rocío Valbuena-Mendoza;M. Włodarczyk-Biegun;A. del Campo
中科院分区:
材料科学2区
文献类型:
--
作者:
Julieta I. Paez;Aleeza Farrukh;Rocío Valbuena-Mendoza;M. Włodarczyk-Biegun;A. del Campo

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巯基马来酰亚胺和巯基乙烯砜交联水凝胶在3D培养模型中广泛使用,尽管在细胞包封反应动力学中表现得不舒服:太快(巯基马来酰亚胺的反应速度为秒)或太慢(巯基乙烯砜的反应速度为分钟-小时)。在这里,我们介绍了巯基甲基砜反应作为细胞包封的替代交联化学反应,特别是peg -水凝胶。在生理pH范围内,硫醇-甲基砜反应发生在高转化率和中等反应速度(秒-分钟)下。这些特性使水凝胶前体和细胞容易混合,在舒适的实验时间尺度上呈现均匀的细胞负载凝胶。所得的水凝胶具有细胞相容性,并表现出与巯基乙烯砜凝胶相当的水解稳定性。它们允许直接生物偶联的硫醇衍生配体和可调节的降解动力学与可降解肽序列交联。三维细胞培养的两种细胞类型,成纤维细胞和人脐静脉内皮细胞(HUVECs),证明。
Thiol-maleimide and thiol-vinylsulfone crosslinked hydrogels are widely used systems in 3D culture models, in spite of presenting uncomfortable reaction kinetics for cell encapsulation: too fast (seconds for thiol-maleimide) or too slow (minutes-hours for thiol-vinylsulfone). Here, we introduce the thiol-methylsulfone reaction as alternative crosslinking chemistry for cell encapsulation, particularized for PEG-hydrogels. The thiol-methylsulfone reaction occurs at high conversion and at intermediate reaction speed (seconds-minutes) under physiological pH range. These properties allow easy mixing of hydrogel precursors and cells to render homogeneous cell-laden gels at comfortable experimental timescales. The resulting hydrogels are cytocompatible and show comparable hydrolytic stability to thiol-vinylsulfone gels. They allow direct bioconjugation of thiol-derivatized ligands and tunable degradation kinetics by crosslinking with degradable peptide sequences. 3D cell culture of two cell types, fibroblasts and human umbilical vein endothelial cells (HUVECs), is demonstrated.