Gelatin-Based Coating for the Controlled and Localized Delivery of Tetrabranched Antimicrobial Peptide in Cardiac Implantable Devices.

Infections associated with cardiac implantable electronic devices (CIEDs) significantly increase patient morbidity and mortality and impose a substantial burden on healthcare systems. Current preventive strategies based on antibiotics are increasingly challenged by the emergence of antimicrobial resistance, while complex surface modification approaches often suffer from limited practicality and translational barriers. In this study, we propose the integration of a structurally complex, tetra-branched antimicrobial peptide (SET-M33) within a gelatin methacryloyl (GelMA) hydrogel to create an antimicrobial-releasing coating for CIED surfaces. By tuning the properties of the GelMA matrix, we achieved controlled peptide release tailored to clinically relevant timeframes. The resulting M33-GelMA coating demonstrated strong in vitro efficacy in preventing bacterial growth and adhesion by six clinically relevant pathogens (Staphylococcus aureus, Staphylococcus epidermidis, Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Stenotrophomonas maltophilia), achieving up to a 9-log reduction in bacterial load. Overall, this work provides a practical and translatable strategy for leveraging more stable, next-generation antimicrobial peptides to reduce postoperative CIED infections and associated healthcare burdens.