Injectable Gelatin-PEG Hydrogels Obtained via Cytochrome C-mediated Polymerization

Abstract

Injectable hydrogels, capable of rapid in situ gelation under physiological conditions, are highly attractive for minimally invasive surgery and locoregional drug delivery. However, the wide majority of polymeric systems rely on UV photo-crosslinking strategies, or slow covalent bond formation limiting in vivo applicability. As a biocompatible alternative, we herein report a three novel injectable hydrogels composed of gelatin methacrylate (GelMA) and poly(ethyleneglycol) dimethacrylate (PEGDA), crosslinked through a Fenton-like radical polymerization mediated by Cytochrome C (CyC) in the presence of H2O2 and L-ascorbic acid. The resulting hydrogels, undergoing a sol–gel transition within 1.0 and 2.0 minutes, are biocompatible and their properties are highly tunable. Indeed, rheological analysis showed that mechanical properties and the linear viscoelastic region (LVR) can be easily modulated by varying the concentrations of the starting methacryl-functionalized gelatin and crosslinker. Structural characterization and biodegradation studies revealed that enzymatic degradation is strongly dependent on the degree of crosslinking. All hydrogels were readily injectable and showed no detectable cytotoxicity in conditioned media assays. Sustained release of rhodamine 101, as a drug mimicking system, reached ~70% over 7 days.