(568c) Brain Regeneration after Stroke Using Injectable Gelatin Methacryloyl (GelMA) Granular Hydrogel Scaffolds

Stroke is a leading cause of disability worldwide. To date, injection of porous scaffolds into stroke cavity has decreased scar thickness and improved the neural progenitor cell (NPC) migration toward the cavity site, promoting brain regeneration. However, the effect of porosity and local stiffness on cell infiltration and immune response after stroke have remained unexplored. In this study, GelMA (gelatin modified with methacrylic anhydride) was used as a biopolymer to fabricate injectable hydrogel microparticles (HMP) followed by assembling granular hydrogel scaffold (GHS) via enzymatic crosslinking. Based on a design of experiments (DOE) method, the local stiffness of GelMA HMP was optimized to mimic the native brain stiffness, ranging from 100 to 1500 Pa. In vitro studies using human astrocyte (HA) were conducted to optimize cell infiltration, metabolic activity, and viability. An in vivo mouse model of brain stroke will be used to investigate the capability of DOE-optimized GHS in reducing scar thickness and inflammation, as well as enhancing the cell infiltration toward the stroke cavity site. This study establishes the foundation for engineering regenerative GelMA GHS in brain regeneration.