Adhesivity-tuned bioactive gelatin/gellan hybrid gels drive efficient wound healing

Gelatin-based hydrogels have been widely used for wound healing applications. However, increase in ligand density and reduction in pore size with increasing gelatin concentration may delay wound healing by limiting cell infiltration. In this study, we address this shortcoming by combining gelatin with gellan-which is super hydrophilic and non-adhesive to cells. We show that UV crosslinked hybrid gels composed of methacrylated gelatin (GelMA) and methacrylated gellan gum (mGG), possess considerably larger pores and improved mechanical properties compared to GelMA gels. Reduced spreading and reduced formation of focal adhesions on hybrid gels combined with lower contractility and faster detachment upon trypsin-induced de-adhesion suggests that hybrid gels are less adhesive than GelMA gels. Gradual release of fibroblast growth factor (FGF) and silver nanoparticles (AgNPs) incorporated in hybrid gels not only boosts cell migration, but also confers anti-bacterial activity against gram-positive and gram-negative bacteria at concentrations nontoxic to cells. Full thickness wound healing in Wistar rats revealed increased granulation tissue formation in hybrid gels, fastest epithelialization and highest collagen deposition in rats treated with FGF entrapped hybrid gels. Together, our results demonstrate how adhesive tuning and incorporation of bioactive factors can be synergistically combined for achieving complete wound healing.