A Material Conferring Hemocompatibility.

David J Scurr,Arnold Darbyshire,Anna Rammou,Achala de Mel,William Everett,George Hamilton

doi:10.1038/srep26848

Abstract

There is a need for biomimetic materials for use in blood-contacting devices. Blood contacting surfaces maintain their patency through physico-chemical properties of a functional endothelium. A poly(carbonate-urea) urethane (PCU) is used as a base material to examine the feasibility of L-Arginine methyl ester (L-AME) functionalized material for use in implants and coatings. The study hypothesizes that L-AME, incorporated into PCU, functions as a bioactive porogen, releasing upon contact with blood to interact with endothelial nitric oxide synthase (eNOS) present in blood. Endothelial progenitor cells (EPC) were successfully cultured on L-AME functionalized material, indicating that L-AME -increases cell viability. L-AME functionalized material potentially has broad applications in blood-contacting medical devices, as well as various other applications requiring endogenous up-regulation of nitric oxide, such as wound healing. This study presents an in-vitro investigation to demonstrate the novel anti-thrombogenic properties of L-AME, when in solution and when present within a polyurethane-based polymer.

Highlights

There is a need for biomimetic materials, which can resist thrombosis associated with blood contacting devices which include[1]; cardiovascular implants, such as vascular bypass grafts, synthetic heart valves, vascular access devices, cardiac patches, coatings for stents, pacemakers as well as implants for wound healing
L-Arginine (L-Arg), a commonly occurring amino acid, is an endogenous substrate of nitric oxide synthase (NOS)[6], a family of enzymes including neuronal NOS, endothelial NOS, and inducible NOS, which all catalyze the formation of NO from L-Arg[7]
L-Arg is important in cardiovascular physiology, and L-Arg supplementation in individuals with hypercholesterolemia or atherosclerosis has been shown to improve endothelial function, dependent upon L-Arg concentration and the type of cardiovascular disease[10] There are many analogues of L-Arg that affect the activity of NOS; L-arginine methyl ester (L-AME) has a very similar chemical structure to L-Arg (Fig. 1a)

Summary

Introduction

There is a need for biomimetic materials, which can resist thrombosis associated with blood contacting devices which include[1]; cardiovascular implants, such as vascular bypass grafts, synthetic heart valves, vascular access devices, cardiac patches, coatings for stents, pacemakers as well as implants for wound healing. Ideal materials should possess suitable mechanical properties that provide the required structural support, and mimic the properties of the endothelium; the inner-most blood-contacting tissue in the cardiovascular system. NO has the ability to inhibit platelet aggregation and activation, and produce smooth muscle relaxation through activation of the cyclic guanylate monophosphate (cGMP) pathway[4]. L-Arginine (L-Arg), a commonly occurring amino acid, is an endogenous substrate of nitric oxide synthase (NOS)[6], a family of enzymes including neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), which all catalyze the formation of NO (along with citrulline) from L-Arg[7]. L-AME is highly soluble in water, and crystalizes when precipitated from solution. For surgical implants, as it facilitates cell-material interactions as well as angiogenesis through the movement of molecules and nutrients within the polymeric scaffold[15,16]

Methods

Results

Conclusion