Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel

Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel:

This work describes the development of a synthetic brain‐mimicking hydrogel. The human brain is characterized mechanically and proteomically, and a modulus and protein composition characteristic of the human brain is defined. Using this brain‐mimicking hydrogel, astrocyte quiescence and activation is controlled via hydrogel composition or soluble cytokines, not possible in other in vitro systems.

Abstract

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.