Biocompatible photo-cross-linked PEG/HA antibacterial hydrogels for pacemaker infection prevention: <i>in vitro</i> and <i>in vivo</i> studies

Infections associated with cardiovascular implantable electronic devices (CIEDs), such as pacemakers, remain a significant complication, often leading to device failure and patient morbidity. Prevention of CIED infection is of the utmost importance for achieving desirable outcomes. This study develops a novel adhesive and antibacterial hydrogel coating, composed of polyethylene glycol (PEG) and hyaluronic acid (HA), to prevent infection associated with CIED. In particular, the hydrogel was photo-cross-linked using 1,4-butanediol diglycidyl ether (BDDE) to enhance stability and moldability, making it suitable for application on CIED surfaces. <i>In vitro</i> cytocompatibility of PEG/HA hydrogel was assessed on L929 fibroblast cells using Live/dead assay and CCK-8 assay. It exhibited remarkable biocompatibility, as indicated by the high cell viability (&gt;90%) in all groups at 24 h, and also the PEG/HA hydrogels caused negligible hemolysis. Apart from that, 0.5 mg/mL of PEG/HA hydrogels showed potent <i>in vitro</i> antibacterial action against both Gram-positive <i>Staphylococcus aureus</i> (20.13 ± 0.71 mm) and Gram-negative <i>Pseudomonas aeruginosa</i> (19.58 = ± 0.98 mm) bacteria. The <i>in vivo</i> antibacterial activity was used to evaluate the CIED pocket infection in a rat model on Days 3 and 7, in which PEG/HA hydrogel effectively reduces the bacterial infection and inflammatory markers compared to controls. This outcome highlights that the PEG/HA hydrogel has a strong potential for preventing CIED pocket infections, offering a promising strategy for enhancing the safety and longevity of cardiovascular pacemaker implants. Development of photo-cross-linkable antibacterial PEG/HA hydrogel to prevent infection associated with CIED. <i>In vitro</i> biocompatibility showed &gt;90% cell viability on L929 fibroblast cells and negligible hemolysis. PEG/HA displayed effective In <i>vitro</i> antibacterial activity against <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa.</i> <i>In vivo</i> antibacterial of PEG/HA has strong potential for preventing CIED infections and improving pacemaker safety.