Antimicrobial and Anti-Thrombogenic Features Combined in Hydrophilic Surface Coatings for Skin-Penetrating Catheters. Synergy of Co-embedded Silver Particles and Heparin

Percutaneous (skin-penetrating) catheters such as central venous catheters (CVCs), are used ubiquitously in the treatment of critically ill patients, although it is known that the risks for serious complications, particularly bloodstream infection and thromboembolism, are high. Materials science and engineering offer important new perspectives regarding further improvement of CVCs. A promising approach is the use of synthetic biocompatible hydrogel coatings with both silver particles and heparin embedded therein. Such formulations combine the well-known broad-spectrum antimicrobial features of silver with the anticoagulant activity of immobilized heparin. Previous work revealed that heparin augments antimicrobial activity of silver, while maintaining its anticoagulant function. This study set out to investigate the synergy of heparin and silver in more detail. Exit-challenge tests, experiments on bacterial killing and adherence, as well as in vitro challenge tests with three Staphylococcus aureus strains (one reference strain, and two clinical isolates) consistently showed the synergistic effect. In addition, the impact of changing the coating's hydrophilicity, and changing the silver concentration in the. coatings, were examined. The experimental results, taken together and combined with data from the literature, point out that synergy of heparin and silver is best explained by binding of Ag+ ions to heparin within the swollen coating, followed by release of heparin-Ag+ complexes upon immersion of the coatings in an aqueous environment such as blood. Possible implications of this work regarding the development of improved/safer CVCs are briefly discussed.