Bioengineers have designed numerous instructive brain extracellular matrix (ECM) environments with tailored and tunable protein compositions and biomechanical properties in vitro to study astrocyte reactivity during trauma and inflammation. However, a major limitation of both protein-based and synthetic model microenvironments is that astrocytes within fail to retain their characteristic stellate morphology and quiescent state without becoming activated under "normal" culture conditions. Here, a synthetic hydrogel is introduced, which for the first time demonstrates maintenance of astrocyte quiescence and activation on demand. With this synthetic brain hydrogel, the brain-specific integrin-binding and matrix metalloprotease-degradable domains of proteins are shown to control astrocyte star-shaped morphologies, and an ECM condition that maintains astrocyte quiescence with minimal activation can be achieved. In addition, activation can be induced in a dose-dependent manner via both defined cytokine cocktails and low molecular weight hyaluronic acid. This synthetic brain hydrogel is envisioned as a new tool to study the physiological role of astrocytes in health and disease.

中文翻译：

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合成脑水凝胶中星形胶质细胞静止和激活的控制。

生物工程师设计了许多具有指导意义的脑细胞外基质（ECM）环境，这些环境具有定制的和可调节的蛋白质组成以及体外生物力学特性，以研究创伤和炎症期间的星形胶质细胞反应性。但是，基于蛋白质的模型和合成模型的微环境的主要局限性在于其中的星形胶质细胞无法保持其特征性的星状形态和静态，而不会在“正常”培养条件下被激活。在这里，介绍了一种合成的水凝胶，这首次证明了星形胶质细胞的静止和按需激活。使用这种合成的脑水凝胶，可以证明脑特异性整联蛋白结合蛋白和基质金属蛋白酶可降解结构域可以控制星形胶质细胞的星形形态，并且可以实现维持星形胶质细胞静止且激活最少的ECM条件。另外，可以通过确定的细胞因子混合物和低分子量透明质酸以剂量依赖的方式诱导活化。该合成脑水凝胶被设想为研究星形胶质细胞在健康和疾病中的生理作用的新工具。