Microgel Aspect Ratio Influences Injectable Granular Hydrogel Scaffold Pore Structure and Cellular Invasion for Tissue Repair

Granular hydrogels are emerging as an important class of scaffolds for biomedical applications, due to their injectability and pore structure to support cellular infiltration. Past research has primarily focused on spherical microgels, which allows limited control over granular hydrogel pore size and void volume fraction; however, investigation into microgels with higher aspect ratios has allowed even higher porosity. This study explores the impact of hyaluronic acid microgel aspect ratio (ranging from 3 to 5) on granular hydrogel porosity and cellular interactions. Both simulations and experimental results show increased void volume fractions and pore sizes in granular hydrogels formed from rod-like microgels when compared to volume-matched spherical microgels, which results in increased cellular invasion with an endothelial cell spheroid migration assay. Injection of the hydrogels into a confined space alters particle packing and void space, but porosity is still higher when rod-like microgels are used, which results in increased cellular invasion when injected subcutaneously. Finally, the highest aspect ratio microgels are used as injectable granular hydrogels to treat myocardial infarction in rats and show reduced infarct area and enhanced functional outcomes when compared to untreated controls. This work provides further insight into microgel shape considerations for engineered granular hydrogels.