Delivery of a novel porous hybrid thermoresponsive hydrogel into the stroke infarct reduces reactive astrogliosis and promotes neural progenitor cell proliferation

Stroke remains a leading cause of adult disability worldwide mainly due to brain′s limited regeneration and repair mechanisms. In the acute and into the chronic phases of ischemic stroke, reactive astrogliosis serves as a major barrier to improvements in neuroplasticity and tissue regeneration. Currently, no therapies are available to regenerate brain tissue lost due to stroke. Here, in a mouse model of photothrombotic stroke, we demonstrate that a hydrogel formulation made from chitosan and β-glycerophosphate as well as hybrid hydrogel formulations developed by combining chitosan, silk fibroin, polyvinyl alcohol, polyvinyl pyrrolidone, and β-glycerophosphate significantly reduce reactive gliosis in the peri-infarct tissue after stroke. We also show that these hybrid hydrogel formulations retain thermoresponsive gelation properties at physiological temperature and are injectable into a stroke cavity in vivo. In addition, the hybrid hydrogel formulations were biocompatible, biodegradable and demonstrated desirable porous microstructure characteristics. To the best of our knowledge, this is the first report demonstrating the neuroprotective potential of CS / β-GP-based hydrogels in dampening reactive astrogliosis following stroke, which would allow these hybrid hydrogels to be combined with drug- or cell-based therapies to enhance functional recovery.