Cell-Interactive Gelatin-Based 19F MRI Tracers: An In Vitro Proof-of-Concept Study

Cross-linked gelatin-based hydrogels are highly promising cell-interactive, biocompatible, and biodegradable materials serving tissue engineering. Moreover, gelatins with covalently bound methacrylamide (gel-MA) and 2-aminoethyl methacrylate moieties (gel-AEMA) can be cross-linked through ultraviolet (UV) irradiation, which allows light-based three-dimensional (3D)-printing of such hydrogels. Furthermore, the physicochemical and biological properties of these hydrogels can be broadly tuned by incorporating various comonomers into the polymer chains, which makes these hydrogels a widely applicable platform in tissue engineering and reconstructive surgery. However, monitoring the degradation rate of hydrogel-based implants in vivo is challenging, thereby prohibiting their broad clinical transition and further research. Therefore, herein, we describe the synthesis of 3D-printable gelatin-based hydrogels with N-(2,2-difluoroethyl)­acrylamide (DFEA), detectable with the chemical shift of −123 ppm, which enables us to monitor these implants in vivo with 19F magnetic resonance imaging (MRI) and assess their degradation kinetics. Next, we describe the physicochemical and biological properties of these hydrogels. Adding DFEA monomers into the reaction mixture accelerates their cross-linking kinetics. Moreover, increasing the DFEA content within the hydrogels increases their swelling ratio and 19F MRI signal. All hydrogels were detectable at small quantities (