Elsevier

Biomaterials

Volume 32, Issue 5, February 2011, Pages 1264-1269
Biomaterials

Hydrophilic surface coatings with embedded biocidal silver nanoparticles and sodium heparin for central venous catheters

https://doi.org/10.1016/j.biomaterials.2010.10.042Get rights and content

Abstract

Central venous catheters (CVCs) have become indispensable in the treatment of neonates and patients undergoing chemotherapy or hemodialysis. A CVC provides easy access to the patient’s circulation, thus enabling facile monitoring of hemodynamic parameters, nutritional support, or administration of (cytostatic) medication. However, complications with CVCs, such as bacterial bloodstream infection or thromboembolism, are common. Bloodstream infections, predominantly caused by Staphylococcus aureus, are notoriously difficult to prevent and treat. Furthermore, patients receiving infusion therapy through a CVC are at risk for deep-vein thrombosis, especially of the upper limbs. Several recent clinical trials have shown that prophylactic anticoagulation (low-molecular-weight heparin or vitamin K antagonists) is not effective. Here, we report on the systematic development of a new bifunctional coating concept that can –uniquely– be applied to make CVC surfaces antimicrobial and antithrombogenic at the same time. The novel coating consists of a moderately hydrophilic synthetic copolymer of N-vinylpyrrollidinone (NVP) and n-butyl methacrylate (BMA), containing embedded silver nanoparticles (AgNPs) and sodium heparin. The work demonstrates that the AgNPs strongly inhibit adhesion of Saureus (reference strain and clinical isolates). Surprisingly, heparin not only rendered our surfaces practically non-thrombogenic, but also contributed synergistically to their biocidal activity.

Introduction

Central venous catheters (CVCs) are used ubiquitously during treatment of critically ill cancer patients. According to recent estimates, more than 5 million cancer patients in the US require central venous access each year [1]. A similar estimate was made for Europe. CVCs offer important advantages, such as facile sustained administration of cytostatic or pain-killing medication, infusion of stem cells, continuous measurement of hemodynamic parameters, or sustained nutritional support. However, application of CVCs is associated with a significant risk for adverse effects, particularly bloodstream infection [2], [3], [4], [5] and thromboembolism [6], [7], [8], [9], [10]. In the US, approximately 80,000 CVC-related nosocomial bloodstream infections occur annually. The associated extra cost is in the range of $300 million to $2.3 billion per year, and the attributable mortality is around 20%. On an average, survivors usually remain one extra week in the intensive care unit, or 2–3 additional weeks in the hospital.

Hence, prevention of CVC-related complications is of paramount importance. Regarding infection, preventive strategies include the use of (i), a maximum sterile barrier during CVC insertion; (ii), innovative catheter hubs, and (iii), chlorhexidine-containing cutaneous antiseptics [2], [3], [4], [5], [11]. Moreover, strict adherence to evidence-based protocols for hygiene and sterility proved highly successful [11]. Prevention of thrombotic complications is mostly attempted through administration of anticoagulants during treatment [6], [7], [8], [9], [10]. Despite all efforts, it is evident that there is a need for improved biomaterials for the manufacture of safer catheters. Engineering into this direction must focus of the catheter’s surface, which must have broad-spectrum antimicrobial activity as well as excellent blood compatibility. We describe the systematic development of new bifunctional surface coatings that –uniquely– meet these requirements.

Section snippets

Formulation

Six different coating solutions were prepared as follows: (i), 600 mL of 10% solution of the hydrophilic copolymer (SS) in NMP was equally divided over six 500 mL glass bottles. (ii), Sodium heparin (3 × 1.5 g, purchased from Celsus Laboratories, Cincinnati, OH, USA) was dissolved (mechanical stirring) in formamide (75 mL). The solution was split into 3 equal parts, and these were mixed with 3 of the SS solutions as indicated in Table 1. (iii), AgNPs (Ag6V or Ag4E; 3.0 g, purchased from Metalor

Results

The continuous coating process afforded a huge inventory of virtually identical specimens for every formulation. This approach distinguishes this study from other investigations on biomaterial surface coatings obtained through dipping or spraying, which are discontinuous methods that generally introduce substantial noise in subsequent experimental data. Specimens were first studied with X-ray photoelectron spectroscopy (XPS). Fig. 1a shows a representative wide-scan spectrum. Data were

Discussion

Hydrophilic surface coatings for medical devices have drawn widespread attention during the last years. Adherent hydrophilic coatings provide catheters and guidewires with a “slippery-when-wet” lubricious surface, and this is extremely important for indwelling catheters, but also for delicate interventional procedures, such as percutaneous transluminal coronary angioplasty (PTCA) and super-precise embolization of solid tumors. New developments are focused on embedding of active components in

Conclusion

Hydrophilic surface coatings for medical devices featuring both biocidal and non-thrombogenic behavior can be prepared. The methodology as described in this work can be scaled-up and transformed into an industrial procedure. This work may help to realize the goal of manufacturing catheters and other medical devices that combine excellent biocidal properties with zero or close-to-zero thrombogenicity in vivo.

Acknowledgements

Part of this work was financed by the Deutsche Forschungsgemeinschaft through the Graduiertenkolleg “BioInterfaces – Detektion und Steuerung Grenzflächeninduzierter, Biomolekularer und Zellulärer Funktionen” (GRK 1035/2). The Universities of Aachen, Liège and Maastricht cooperate within this Graduiertenkolleg.

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