(275d) Increasing Cell Infiltration in Granular Hydrogel Scaffolds Via Porous Microgel Building Blocks

Hydrogels have emerged as promising biomaterials for tissue engineering by providing three-dimensional (3D) microenvironments that mimic the native extracellular matrices (ECM). However, bulk (nanoporous) hydrogels lack interconnected cell-scale pores, which hinders cell infiltration, an essential process for tissue regeneration. Granular hydrogel scaffolds (GHS), formed via the assembly of hydrogel microparticles (microgels) address this limitation by providing microscale void spaces among the microgels, enabling nutrient diffusion and cell infiltration/migration. Yet, the widespread use of spherical microgels in GHS fabrication limits void fraction, a critical factor in facilitating nutrient diffusion and cell infiltration. In this study, we developed porous spherical microgels via the thermally induced phase separation of composite gelatin methacryloyl (GelMA) polymers and assembled them into GHS, enabling hierarchical porosity at particle and scaffold levels. Void volume fraction significantly increased in GHS incorporating porous microgels compared with their nonporous counterparts. In vitro cell infiltration into porous microgels was higher in microgels comprising larger pores, as indicated by the total cell volume infiltrated in individually crosslinked microgels. In vivo, cell infiltration was significantly higher in subcutaneously implanted GHS made up of porous microgels, promoting host tissue integration. This research underscores the potential of porous microgels in creating GHS with tailored structural and mechanical properties, offering a new biomaterial platform for tissue engineering and regeneration.