Fig. 7: Schematic illustration of the effects of GelMA crosslinking on wound healing.

Low crosslinked (lo-GelMA) hydrogels, treated with 1 minute of UV exposure, are soft (3 kPa) and porous, promoting cell infiltration and integration into wound tissue. Wound repair with lo-GelMA is characterized by Mϕ phagocytosis and pro-healing activities, fibroblast chemotaxis and proliferation, and collagen maturation in the hydrogel, leading to reduced scarring. High crosslinked (hi-GelMA) hydrogels, treated with 5 minutes of UV exposure, are stiff (150 kPa) and nonporous, impeding cell infiltration and subsequent tissue integration. Wounds treated with hi-GelMA display enhanced inflammation and fibrosis, associated with Mϕ pro-inflammation activities and fibroblast pro-fibrotic activation. This response includes Mϕ expressing pro-inflammatory and pro-fibrotic genes Il1b, TGFb, PDGFB, OSM, and Tnfrsf11a (receptor for the RANKL signal), with pro-fibrotic fibroblasts expressing its ligand Tnfsf11 (RANKL). Moreover, hi-GelMA promotes Mϕ fusion into FBGC at the tissue-biomaterial interface, leading to elevated levels of ROS and MMPs. Mϕ in contact with the hydrogels exhibit expression of integrins Itgal, Itgax, Itgb2, and ItgaV facilitating tissue integration. Figure 7 created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license (https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en).