(580b) Engineering Biomacromolecular Granular Hydrogel Scaffolds to Enhance Wound Healing Quality

Scaffold-based wound healing therapies have shown significant improvements in the rate and quality of healing. To further improve these therapies, hydrogel microparticle (HMP) have been fabricated as building blocks and assembled into granular hydrogel scaffolds (GHS), facilitating cell ingrowth and reducing inflammation. Despite the extensive use of bulk gelatin methacryloyl (GelMA) hydrogel scaffolds for wound healing, the potential of GelMA GHS for this purpose remains unexplored. In this study, GHS was formed by photocrosslinking GelMA HMP, and mechanical characterizations were conducted on the GHS with two different HMP sizes. The median pore equivalent diameter and compression modulus of GHS were analyzed to optimize scaffold porosity for cell infiltration and proliferation. The effect of GHS porosity on macrophage behavior was compared with bulk (non-porous) GelMA scaffolds. A murine model of full-thickness skin injury was used to assess the effect of porosity on wound healing in vivo. Although the rate of wound closure was not affected by porosity, hematoxylin and eosin (H&E) and immunofluorescence staining at 11 days post-implantation showed a thicker granulation tissue, attesting to an improved wound healing quality for GelMA GHS compared with the bulk scaffolds. The results obtained from both in vitro and in vivo experiments demonstrate that GelMA GHS improves tissue regeneration. This study provides the foundation for developing GelMA GHS for regenerative applications.