Multiphasic microgel-in-gel materials to recapitulate cellular mesoenvironments in vitro
Multiphasic microgel-in-gel materials to recapitulate cellular mesoenvironments in vitro
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DOI：
10.1039/c9bm01009b
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发表时间：
2020-01-01
影响因子：
6.6
通讯作者：
Werner, Carsten
中科院分区：
文献类型：
--
作者：
Husman, Dejan;Welzel, Petra B.;Werner, Carsten
具有基质性质和/或细胞组成的跨尺度异质性的多相体外模型可以更忠实地反映活组织的结构和组成复杂性，从而为病理生物学和药物开发研究创造新的选择。在本文中，报道了一类新的可调微凝胶包凝胶材料，其建立在多功能聚（乙二醇）-肝素凝胶类型的通用平台上，并将单分散的载有细胞的微凝胶整合在载有细胞的散装水凝胶基质中。开发了一种新的微流控方法，以实现原位可调直径，刚度，降解性和生物分子功能化的微凝胶的高通量制造。通过独立地选择微凝胶和散装凝胶隔室的结构和组成，我们的微凝胶在凝胶中的布置提供了对组织模拟特征的跨尺度控制，并为具有设计的中环境特征的培养系统铺平了道路。通过创建血管化前列腺癌组织的简化体外模型示例性地显示了所引入的方法的潜力。
Multiphasic in vitro models with cross-scale heterogeneity in matrix properties and/or cellular composition can reflect the structural and compositional complexity of living tissues more faithfully, thereby creating new options for pathobiology and drug development studies. Herein, a new class of tunable microgel-in-gel materials is reported that build on a versatile platform of multifunctional poly(ethylene glycol)-heparin gel types and integrates monodisperse, cell-laden microgels within cell-laden bulk hydrogel matrices. A novel microfluidic approach was developed to enable the high-throughput fabrication of microgels of in situ adjustable diameters, stiffness, degradability and biomolecular functionalization. By choosing structure and composition of the microgel and the bulk gel compartments independently, our microgel-in-gel arrangements provide cross-scale control over tissue-mimetic features and pave the way for culture systems with designed mesoenvironmental characteristics. The potentialities of the introduced approach are exemplarily shown by creating a reductionistic in vitro model of vascularized prostate cancer tissue.