Leibniz-Institut für Polymerforschung Dresden e.V. (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), Hohe Str. 6, 01069 Dresden, Germany.
Biomater Sci. 2019 Dec 17;8(1):101-108. doi: 10.1039/c9bm01009b.
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.
多相体外模型具有基质特性和/或细胞组成的跨尺度异质性，可以更真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。本文报道了一类新的可调微凝胶-凝胶材料，该材料基于多功能聚乙二醇-肝素凝胶类型的通用平台，并在细胞填充的块状水凝胶基质内集成了单分散的、细胞填充的微凝胶。开发了一种新的微流控方法，可实现具有原位可调直径、刚度、降解性和生物分子功能化的微凝胶的高通量制造。通过独立选择微凝胶和大块凝胶隔室的结构和组成，我们的微凝胶-凝胶排列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，示例说明了所提出方法的潜力。
