Gelatin methacryloyl granular hydrogel scaffolds for skin wound healing

The pore size and structure of hydrogel scaffolds play a key role in regulating host-scaffold interactions. Incorporating macropores within bulk hydrogels may increase cell ingrowth and modulate scaffold-induced inflammation. To this end, granular hydrogel scaffolds (GHS) have been developed <i>via</i> assembling hydrogel microparticles (microgels). GHS have interconnected cell-scale pores, tailored by microgel size, which are readily accessible to cells. Although bulk gelatin methacryloyl (GelMA) hydrogel scaffolds have frequently been used for tissue regeneration, the efficacy of GelMA GHS in wound healing remains unknown. Here, GelMA GHS are fabricated using microfluidic-generated near-uniform microgels to study the effect of macropores on macrophage behavior <i>in vitro</i>, followed by assessing wound healing in a murine model of full thickness skin injury. Compared with the bulk hydrogel counterpart, macrophages interfaced with GHS secrete less interferon gamma (IFN-γ) and more insulin-like growth factor 1 (IGF-1), which show a transition to pro-healing activities. In addition, GelMA GHS improve the quality of wound healing <i>via</i> increasing the thickness of granulation tissue and downregulating inflammatory markers without affecting the wound closure rate. This work is a step forward in engineering GelMA scaffolds with tailored porosity for wound care.