Title:
Development of an anti-thrombotic and anti-biofilm surface for application in vascular access technology

R. Dietrich¹ ;R. Dietrich¹ ;R. Dietrich¹ ;R. Dietrich² ;R. Dietrich³ ;R. Dietrich³ ;R. Dietrich¹

Germany' ne '' Germany' ne '' Germany' ne ''

E-mail address corresponding author:
ruth.dietrich@gambro.com

Background:
Bacterial adhesion and biofilm (BF) formation on invasive medical devices is an essential cause of bloodstream infections, e.g. with central venous catheters for vascular access in hemodialysis. Bloodstream infections are associated with prolonged hospitalisation, high mortality and huge costs that may reach a multiple of 10,000 $ per case. Limited pharmacological accessibility of bacteria within a BF and the increase of resistance to antibacterial drugs in bacterial strains, e.g. MRSA, add considerably to this problem. Several approaches, e.g. antimicrobial impregnation with chlorhexidine-silver sulfadiazine, antibiotics etc., face potential drawbacks such as unintentional release and unclear long-term toxicology of active substances.

Methods:
A bio-functional catheter coating based on PUR-PDMS co-polymer was developed to approach this clinically and socio-economically relevant issue. The smoothing, nano-domain structured film coating prevents surface degradation and limits protein adsorption and blood cell deposition/activation, thus providing minimal thrombogenicity and enhanced biocompatibility. The crosslinked polymer film contains a non-releasing bismuth complex with repulsive properties to reduce bacteria deposition and proliferation, a well-known prerequisite for BF formation. Thrombogenicity was assessed by recirculation of fresh human plasma and analysis of thrombin-antithrombin III complex (TAT). Cytotoxicity was measured in a fibroblast proliferation assay (FPA). BF formation was followed with confocal laser scanning microscopy (CLSM) after exposure to 30 million bacteria for 96 hours at 37°C and live/dead staining.

Results:
TAT generation was significantly lower on the coated catheter surface compared with the standard catheter after 60 min (159 vs. 841 µg/L). FPA resulted in an inhibition of cell growth below 20%, which is well below the defined cytotoxicity limit of 30%. CLSM revealed only a minimal number of dead bacteria and complete prevention of BF formation on the bismuth-functionalized surface coating, whereas on the standard catheter surface vital adherent bacteria and pronounced BF formation were detected. Surface degradation usually occurring with barium sulphate (radio contrast agent) containing catheters is prevented by the coating as shown in clinical investigations. This results in a smooth, multifunctional surface with non-thrombogenic, non-adhesive, non-degrading, non-cytotoxic but anti-BF properties, thus addressing different steps in the sequence of BF and clot formation.

Conclusion:
This technology may be applied to many kinds of medical devices. Application of this type of functional anti-biofilm access system reduces the risk of bacterial colonisation and might have a beneficial effect on the occurrence of device-related bloodstream infections in clinical practice, however broader clinical experience is required.

Subject:
Vascular Access

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