(M-491) Injectable gelatin methacryloyl (GelMA) granular hydrogel scaffolds for brain regeneration after stroke

Introduction:: 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 effects of porosity and local stiffness on cell infiltration and immune response after stroke have remained unexplored.


Materials and Methods:: GelMA (gelatin methacryloyl) was used as a biopolymer to fabricate injectable hydrogel microparticles (HMP), followed by assembling granular hydrogel scaffold (GHS) via enzymatic crosslinking (Fig. 1a). 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.


Results, Conclusions, and Discussions:: The local stiffness of the GelMA HMP was optimized by altering the GelMA concentration, photoinitiator (PI) concentration, duration of crosslinking via UV light exposure, and GelMA degree of substitution (DS) (Fig. 1b). Further, GHS formation and injectability were analyzed (Fig. 1c). DOE-based in vitro studies show the effect of local GelMA HMP stiffness and GHS pore size on metabolic activity, viability, and cell infiltration. This study establishes the foundation for engineering regenerative GelMA GHS in brain regeneration.

Acknowledgements (Optional): : Research reported in this publication was supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number R01NS121150. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


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