Competitive adsorption of plasma proteins on polysaccharide-modified silicon surfaces

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Competitive adsorption of plasma proteins on polysaccharide-modified silicon surfaces Michela Ombelli1, Lauren B. Costello2, Qing Cheng Meng1, Russell J. Composto2,3, David M. Eckmann1,4 1 Department of Anesthesia, University of Pennsylvania, 2 Department of Materials Science and Engineering, University of Pennsylvania, 3 Center for Bioactive Materials and Tissue Engineering, University of Pennsylvania, 4 The Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA, 19104, U.S.A. ABSTRACT The initial response of blood exposed to an artificial surface is the adsorption of blood proteins that triggers a number of biological reactions such as inflammation and blood coagulation. Competitive protein adsorption plays a key role in the hemocompatibility of the surface. The synthesis of nonfouling surfaces is therefore one of the major prerequisites for devices for biomedical applications. Polysaccharides are the main components of the endothelial cell glycocalyx and have the ability to reduce nonspecific protein adsorption and cell adhesion and, therefore, are generally coupled with a wide variety of surfaces to improve their biocompatibility. We have developed a procedure for covalently binding dextran and sodium hyaluronate (HA) on silicon wafers and we have been able to achieve a high level of control over the surface properties of the coatings. In the present research effort we focus on a detailed investigation of competitive bovine serum albumin (BSA) and bovine fibrinogen (Fg) adsorption on dextran- and HA-modified silicon surfaces. Polysaccharide based biomimetic layers preferentially adsorb BSA and, in general, strongly suppress protein adsorption with respect to bare silicon and APTES-activated silicon surfaces used as control.

INTRODUCTION Polysaccharides serve as excellent coatings for devices in contact with blood since they are compatible with biological systems and have been shown to reduce protein adsorption and cell adhesion on synthetic surfaces [1]. We have developed a procedure for covalently binding dextran on silicon wafers pre-activated by amine terminated APTES and we have been able to reach a high level of control on the thickness, wettability and roughness of the coatings by varying the molecular weight, polydispersity [2, 3] and the degree of chemical oxidation of the dextrans [4]. We have also demonstrated that monodisperse, high molecular weight dextran coatings applied on microcapillary glass tubes show bubble adhesion properties almost identical to the values found for in vivo and ex vivo experiments of microvascular gas embolism [2]. More recently we have also synthesized hyaluronic acid (hyaluronan, HA) coatings on silicon wafers by using EDC/NHS grafting chemistry [5]. A key event, whenever a biomaterial is exposed to protein-containing fluids is the adsorption of proteins. The exact mechanism of how polymer structure and its chemical/physical properties influence the adsorption and activation behavior of proteins is still unknown, but it is widely assu