Surface Modification of Biomaterials: A Quest for Blood Compatibility

UCL Centre for Nanotechnology & Regenerative Medicine, University College London, Pond Street, London NW3 2QG, UK.
International Journal of Biomaterials 05/2012; 2012(4-5):707863. DOI: 10.1155/2012/707863
Source: PubMed


Cardiovascular implants must resist thrombosis and intimal hyperplasia to maintain patency. These implants when in contact with blood face a challenge to oppose the natural coagulation process that becomes activated. Surface protein adsorption and their relevant 3D confirmation greatly determine the degree of blood compatibility. A great deal of research efforts are attributed towards realising such a surface, which comprise of a range of methods on surface modification. Surface modification methods can be broadly categorized as physicochemical modifications and biological modifications. These modifications aim to modulate platelet responses directly through modulation of thrombogenic proteins or by inducing antithrombogenic biomolecules that can be biofunctionalised onto surfaces or through inducing an active endothelium. Nanotechnology is recognising a great role in such surface modification of cardiovascular implants through biofunctionalisation of polymers and peptides in nanocomposites and through nanofabrication of polymers which will pave the way for finding a closer blood match through haemostasis when developing cardiovascular implants with a greater degree of patency.

Download full-text


Available from: Brian G Cousins,
  • Source
    • "Anticoagulant and platelet adhesion of surface functionalized PCL strips Anticoagulant activity of surface functionalized PCL was quantitatively assessed through surface activated clot formation and subsequent color density analysis (ImageJ Densitometry plugin [27]). This assay is based on the material surfaces ability to absorb plasma proteins leading to fibrin formation and erythrocyte adhesion through thrombin activated Factor XIII activity, firstly forming a red gel like coating which may proceed to the darker red clot formation [28] [29], hence the color intensity and area relate to the anticoagulant properties of the surface. High resolution images were recorded with preset aperture and exposure time. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A straight forward strategy of heparin surface grafting employs a terminal reactive-aldehyde group introduced through nitrous acid depolymerization. An advanced method that allows simultaneously monitoring of both heparin molar mass and monomer/aldehyde ratio by size exclusion chromatography, multi-angle laser light scattering and UV-absorbance (SEC-MALLS-UV) has been developed to improve upon heparin surface grafting. Advancements over older methods allow quantitative characterization by direct (aldehyde absorbance) and indirect (Schiff-based absorbance) evaluation of terminal functional aldehydes. The indirect quantitation of functional aldehydes through labeling with aniline (and the formation of a Schiff-base) allows independent quantitation of both polymer mass and terminal functional groups with the applicable UV mass extinction coefficients determined. The protocol was subsequently used to synthesize an optimized heparin-aldehyde that had minimal polydispersity (PDI<2) and high reaction yields (yield >60% by mass). The 8kDa weight averaged molar mass heparin-aldehyde was then grafted on polycaprolactone (PCL), a common implant material. This optimized heparin-aldehyde retained its antithrombin activity, assessed in freshly drawn blood or surface immobilized on PCL films. Anticoagulant activity was equal to or better than the 24kDa unmodified heparin it was fragmented from. Copyright © 2015 Elsevier B.V. All rights reserved.
    Colloids and surfaces B: Biointerfaces 05/2015; 132. DOI:10.1016/j.colsurfb.2015.05.023 · 4.15 Impact Factor
  • Source
    • "The fact that nanoscale surface topography stimulates and controls several molecular and cellular events at the tissue/implant interface has prompted investigations of such topographies in the design of implantable metals [2] [4] [5]. Nanomodification of Ti generating TiO 2 surfaces has proved beneficial in promoting endothelial proliferation as well as migration onto stent surfaces [8] [9] [10] [11]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The usefulness of nanoscale topography in improving vascular response in vitro was previously established in our study on hydrothermally modified titanium surfaces. To propose this strategy of surface modification for clinical translation onto metallic stents, it is imperative that the surface be also hemocompatible - an essential attribute for any blood contacting device. The present in vitro study focuses on a detailed hemocompatibility evaluation of titania nanostructures created through an alkaline hydrothermal route on metallic Ti stent prototypes. Direct interactions of TiO2 nanocues of varied morphologies with whole blood were studied under static conditions as well as using an in vitro circulation model mimicking arterial flow, with respect to polished Ti control. Nanomodified stent surfaces upon contact with human blood showed negligible hemolysis under constant shear and static conditions. Coagulation profile testing indicated that surface roughness of nanomodified stents induced no alterations in the normal clotting times, with insignificant thrombus formation and minimal inflammatory reaction. Endothelialized nanomodified Ti surfaces were found to inhibit both activation as well as aggregation of platelets compared to the control surface, with the endothelium formed on the nanosurfaces having an increased expression of anti-thrombogenic genes. Such a nanotextured Ti surface which is anti-thrombogenic and promotes endothelialization would be a cost-effective option to drug eluting stents or polymer coated stents for overcoming in-stent restenosis.
    Acta biomaterialia 08/2013; 9(12). DOI:10.1016/j.actbio.2013.08.023 · 6.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic wounds contain elevated levels of proteases, proinflammatory cytokines, and free radicals. The presence of bacteria further exaggerates the tissue-damaging processes. For successful treatment, the wound dressing needs to manage wound exudates, create a moist environment, inhibit infection, bind pathophysiological factors that are detrimental to wound healing, and provide thermal isolation. Furthermore, it has to relieve pain, be easy to use, show no allergic potency, and not release toxic residues. The present study suggests a comprehensive in vitro approach to enable the assessment of wound dressings to support optimal conditions for wound healing. Three alginate-based wound dressings: alginate alone, alginate containing ionic silver, and alginate with nanocrystalline silver, were tested for biocompatibility, antimicrobial activity, and influence on chronic wound parameters such as elastase, matrix metalloproteases-2, tumor necrosis factor-alpha, interleukin-8, and free radical formation. Alginate was found to bind considerable amounts of elastase, reduce the concentration of proinflammatory cytokines and inhibit the formation of free radicals. Furthermore, alginate showed antibacterial activity and high biocompatibility. Incorporation of silver into alginate fibers increased antimicrobial activity and improved the binding affinity for elastase, matrix metalloproteases-2, and the proinflammatory cytokines tested. Addition of silver also enhanced the antioxidant capacity. However, a distinct negative effect of silver-containing alginates on human HaCaT keratinocytes was noted in vitro.
    Wound Repair and Regeneration 07/2009; 17(4):511-21. DOI:10.1111/j.1524-475X.2009.00503.x · 2.75 Impact Factor
Show more