Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin

The tuneability of hydrogels renders them promising candidates for local drug delivery to prevent and treat local surgical site infection (SSI) while avoiding the systemic side-effects of intravenous antibiotic injections. Here, we present a newly developed gelatin methacryloyl (GelMA)-based hydrogel drug delivery system (GelMA-DDS) to locally deliver the broad-spectrum antibiotic cefazolin for SSI prophylaxis and treatment. Antibiotic doses from 3 µg to 90 µg were loaded in photocrosslinked GelMA hydrogel discs with 5 to 15% w/v polymer concentration and drug encapsulation efficiencies, mechanical properties, crosslinking and release kinetics, as well as bacterial growth inhibition were assessed. Our results demonstrate that all GelMA groups supported excellent drug encapsulation efficiencies of up to 99%. Mechanical properties of the GelMA-DDS were highly tuneable and unaffected by the loading of small to medium doses of cefazolin. The diffusive and the proteolytic in vitro drug delivery of all investigated cefazolin doses was characterized by a burst release, and the delivered cefazolin amount was directly proportional to the encapsulated dose. Accelerated enzymatic degradation of the GelMA-DDS followed zero-order kinetics and was dependent on both the cefazolin dose and GelMA concentration (3-13 h). Finally, we demonstrate that cefazolin delivered from GelMA induced a dose-dependent antibacterial efficacy against S. aureus, in both a broth and a diffusive assay. The cefazolin-loaded GelMA-DDS presented here provides a highly tuneable and easy-to-use local delivery system for the prophylaxis and treatment of SSI.