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.