Materials that can mimic the fibrillar architecture of native extracellular matrix (ECM) while allowing for independent regulation of viscoelastic properties may serve as ideal, artificial ECM (aECM) to regulate cell functions. Here we describe an interpenetrating network of click-functionalized alginate, crosslinked with a combination of ionic and covalent crosslinking, and fibrillar collagen type I. Varying the mode and magnitude of crosslinking enables tunable stiffness and viscoelasticity, while altering neither the hydrogel's microscale architecture nor diffusional transport of molecules with molecular weight relevant to typical nutrients. Further, appropriately timing sequential ionic and covalent crosslinking permits self-assembly of collagen into fibrillar structures within the network. Culture of human mesenchymal stem cells (MSCs) in this mechanically-tunable ECM system revealed that MSC expression of immunomodulatory markers is differentially impacted by the viscoelasticity and stiffness of the matrix. Together, these results describe and validate a novel material system for investigating how viscoelastic mechanical properties of ECM regulate cellular behavior.

中文翻译：

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交联的顺序模式可调节细胞指导性水凝胶的粘弹性。

可以模仿天然细胞外基质（ECM）的原纤维结构同时允许粘弹性特性独立调节的材料，可以作为理想的人工ECM（aECM）来调节细胞功能。在这里，我们描述了点击功能化藻酸盐的互穿网络，该网络通过离子和共价交联与I型原纤维胶原蛋白的交联而交联。改变交联的方式和幅度可实现可调的刚度和粘弹性，同时不会改变水凝胶的微尺度结构和扩散性分子量与典型营养物质有关的分子的运输。此外，适当定时的顺序离子和共价交联允许胶原蛋白自组装成网络内的原纤维结构。在这种机械可调的ECM系统中培养人间充质干细胞（MSC）显示，免疫调节标记的MSC表达受到基质的粘弹性和刚度的不同影响。总之，这些结果描述并验证了一种新颖的材料系统，用于研究ECM的粘弹性机械性能如何调节细胞行为。