¹⁹F MRI In Vivo Monitoring of Gelatin-Based Hydrogels: 3D Scaffolds with Tunable Biodegradation toward Regenerative Medicine

Gelatin-based hydrogels emerged as promising biodegradable cell-compatible 3D-printable materials with tunable mechanical properties that serve tissue engineering and applications in regenerative medicine. Nevertheless, these materials are very challenging to monitor in vivo, which has hampered the further development of these materials and their translation into clinical practice. To overcome this limitation, we designed a cross-linked 3D-printable gelatin-based hydrogel endowed with poly[ N -(2,2-difluoroethyl)acrylamide] (PDFEA). Such PDFEA-containing hydrogels can be monitored in vivo through fluorine-19 magnetic resonance imaging ( 19 F MRI), which enables to monitor such implants in vivo and to assess their in vivo biodegradation kinetics. Herein, we prepared three different PDFEA-containing hydrogels with varying cross-linking degrees and studied their physicochemical properties (storage modulus, Young’s modulus, swelling ratio, in vitro degradation rate). Next, we administered these samples subcutaneously into mice and exploited 19 F MRI to detect the biodegradation kinetics over 370 days. Hydrogels with a high cross-linking degree did not extensively degrade in vitro nor in vivo within the evaluated time frame. In contrast, hydrogels characterized by a low degree of cross-linking extensively degraded in vitro as well as in vivo (half-life of 228 ± 21 days). We demonstrated that endowing hydrogels with PDFEA enables monitoring of these hydrogels in vivo . Our results may become a benchmark in forthcoming studies of biodegradable hydrogels and the development of 19 F MRI detectable gelatin-based hydrogels, paving the way toward their entry in clinical practice.