Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 15, 2020
- Source ID
- 10.1002/adhm.201901419
Entities
People
- Alfred J Crosby
- Changhui Pak
- Shelly R. Peyton
- Sualyneth Galarza
Organizations
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institutes of Health
- National Science Foundation
- Office of Naval Research
- University of Massachusetts