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Increasing numbers of individuals live with stroke related disabilities. Following stroke, highly reactive astrocytes and pro-inflammatory microglia can release cytokines and lead to a cytotoxic environment that causes further brain damage and prevents endogenous repair. Paradoxically, these same cells also activate pro-repair mechanisms that contribute to endogenous repair and brain plasticity. Here, it is shown that the direct injection of a hyaluronic acid-based microporous annealed particle (MAP) hydrogel into the stroke core in mice reduces the percent of highly reactive astrocytes, increases the percent of alternatively activated microglia, decreases cerebral atrophy, and preserves NF200 axonal bundles. Further, MAP hydrogel is shown to promote reparative astrocyte infiltration into the lesion, which directly coincides with axonal penetration into the lesion. This work shows that the injection of a porous scaffold into the stroke core can lead to clinically relevant decrease in cerebral atrophy and modulates astrocytes and microglia toward a pro-repair phenotype.

Sideris E, Kioulaphides S, Wilson KL, Yu A, Chen J, Carmichael ST, Segura T