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Infective/bacterial endocarditis is a rare but life-threatening disease with a hospital mortality rate of 22.7% and a 1-year mortality rate of 40%. Therefore, continued research efforts to develop efficient anti-infective implant materials are of the utmost importance. Equally important is the development of test systems that allow the performance of new materials to be comprehensively evaluated. In this study, a novel antibacterial coating based on dalbavancin was tested in comparison to rifampicin/minocycline, and the suitability of a recently developed mouse tail vein model for testing the implant coatings was validated. Small polymeric stent grafts coated with a poly-L-lactic acid (PLLA) layer and incorporated antibiotics were colonized with Staphylococcus (S.) aureus before implantation into the tail vein of mice. The main assessment criteria were the hematogenous spread of the bacteria and the local tissue reaction to the contaminated implant. For this purpose, colony-forming units (CFU) in the blood, spleen and kidneys were determined. Tail cross sections were prepared for histological analysis, and plasma cytokine levels and expression values of inflammation-associated genes were examined. Both antibiotic coatings performed excellently, preventing the onset of infection. The present study expands the range of available methods for testing the anti-infectivity of cardiovascular implants, and the spectrum of agents for effective surface coating.
Abstract: The main purpose of new stent technologies is to overcome unfavorable material-related
incompatibilities by producing bio- and hemo-compatible polymers with anti-inflammatory and antithrombogenic properties. In this context, wettability is an important surface property, which has a
major impact on the biological response of blood cells. However, the influence of local hemodynamic
changes also influences blood cell activation. Therefore, we investigated biodegradable polymers
with different wettability to identify possible aspects for a better prediction of blood compatibility.
We applied shear rates of 100 s−1 and 1500 s−1 and assessed platelet and monocyte activation as
well as the formation of CD62P+ monocyte-bound platelets via flow cytometry. Aggregation of
circulating platelets induced by collagen was assessed by light transmission aggregometry. Via
live cell imaging, leukocytes were tracked on biomaterial surfaces to assess their average velocity.
Monocyte adhesion on biomaterials was determined by fluorescence microscopy. In response to
low shear rates of 100 s−1
, activation of circulating platelets and monocytes as well as the formation
of CD62P+ monocyte-bound platelets corresponded to the wettability of the underlying material
with the most favorable conditions on more hydrophilic surfaces. Under high shear rates, however,
blood compatibility cannot only be predicted by the concept of wettability. We assume that the
mechanisms of blood cell-polymer interactions do not allow for a rule-of-thumb prediction of the
blood compatibility of a material, which makes extensive in vitro testing mandatory.