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 F-19 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 F-19 MRI signal. All hydrogels were detectable at small quantities (<16 mg) using F-19 MRI. Moreover, our hydrogels supported the cell proliferation of adipose tissue-derived stem cells (ASCs) and had tunable biodegradation rates. Finally, we present a strategy for increasing the DFEA content without affecting the mechanical properties. Our results may be implemented in the future development of hydrogel implants, whose fate and biodegradation rate can be monitored via F-19 MRI.