Anti-Infective Bacteriophage Immobilized Nitric Oxide-Releasing Surface for Prevention of Thrombosis and Device-Associated Infections.

The treatment of critically ill patients has made great strides in the past few decades due to the rapid development of indwelling medical devices. Despite immense advancements in the design of these devices, indwelling medical device-associated infections and thrombosis are two major clinical problems that may lead to device failure and compromise clinical outcomes. Antibiotics are the current treatment choice for these infections; however, the global emergence of antibiotic-resistance and their biofilm formation abilities complicate the management of such infections. Moreover, systemic administration of anticoagulants has been used to counter medical device-induced thrombosis, but a range of serious adverse effects associated with all types of available anticoagulants entails exploring alternative options to counter device-associated thrombosis. In this study, bacteriophages (phages) were covalently immobilized on polydimethylsiloxane (PDMS) surface containing the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) via SNAP impregnation method. This dual strategy combines the targeted antibacterial activity of phages against bacterial pathogens with the antibacterial-antithrombotic activity of NO released from the polymeric surface. The PDMS, SNAP-PDMS, phage-immobilized PDMS (PDMS-Phage), and phage-immobilized SNAP-PDMS (SNAP-PDMS-Phage) surfaces were characterized for their surface topology, elemental composition, contact angle, SNAP loading, NO release and phage distribution. SNAP-PDMS and SNAP-PDMS-Phage surfaces showed similar and consistent NO release profiles over 24 h of incubation. Immobilization of whole phages on PDMS and SNAP-PDMS was achieved with densities of 2.4 ± 0.54 and 2.1 ± 0.33 phages μm^-2, respectively. Immobilized phages were found to retain their activity, and SNAP-PDMS-Phage surfaces showed a significant reduction in planktonic (99.99 ± 0.08%) as well as adhered (99.80 ± 0.05%) Escherichia coli as compared to controls in log killing assays. The SNAP-PDMS-Phage surfaces also exhibited significantly reduced platelet adhesion by 64.65 ± 2.95% as compared to control PDMS surfaces. All fabricated surfaces were found to be nonhemolytic and do not exhibit any significant cytotoxic effects toward mammalian fibroblast cells. This study is the first of its kind to demonstrate the combinatorial pertinence of phages and NO to prevent antibiotic-resistant/sensitive bacterial infections and thrombosis associated with indwelling medical devices.