Designed polymer structures with antifouling–antimicrobial properties

Abstract

Designing surfaces with antifouling and antimicrobial properties has an important route to solve problems, such as infections and fouling, in healthcare and industrial applications. Recently, there has been considerable interest in developing surfaces with polymers because of their distinct properties, such as their length scale, their processability, low cost, tunable properties, and diverse functionalities. This article reviews the polymer systems developed as antifouling–antimicrobial surface coatings, termed as biopassive and bioactive polymers respectively. Many different types of bioactive and biopassive polymeric systems and their limitations are presented.

Introduction

Bacterial infection of implanted materials and devices, such as catheters, pacemaker leads, and knee and hip implants, is a major health care problem causing an adverse impact on the quality of life of patients and high costs [1], [2]. Bacterial adherence to implant surfaces occurs in two phases. First, bacteria compete with host cells for binding to the extracellular matrix or plasma proteins on the surface of the device; this is described as “race for the surface”. Then adherent bacteria proliferate and cluster in multilayers of exopolysaccharides into biofilms, which have a low metabolism without toxin production. The introduction of an implant into the body increases susceptibility to biomaterial-centred infection, due to the damage caused to epithelial and mucosal barriers upon implantation. Further the presence of the implant, and the extracellular matrix protein adsorbed onto it, serves as a surface for colonizing bacteria, thereby reducing the minimum inoculum required [3]. Clearance of biofilms by systemically delivered antibiotics is severely hampered by the reduced susceptibility of adherent bacteria to antimicrobial treatment [4], [5]. This resistance may be due to reduced rate of biofilm growth as the bacteria enter a stationary phase of growth or the hampered diffusion of antibiotics. Implant-associated infections tend, therefore, to be persistent and refractory to antibiotics. Successful therapy requires multistep procedures, e.g. removal of the infected device, intravenous and oral therapy with antibiotics for weeks or months and re-implantation of a new device. Many concepts have been explored and described in the literature for preventing infection of implants, including biopassive and bioactive surfaces, either with a covalently attached moiety or one that is released into the surrounding environment.

Materials with antifouling and antimicrobial properties have been the subject of much interest and extensive research. Polymers, having multiple length scales, can be incorporated into different molecular and supramolecular organizations by controlling their length scales, surface chemistries, and mechanical properties leading to development of surfaces that can be utilized in a wide variety of biosystems. For instance, PEG systems have been extensively studied, and PEG immobilized surfaces are shown to decrease the amount of protein adsorbed on biomaterial surfaces. These systems were also explored to reduce the adhesion of bacteria by reducing the contact between the bacteria and the surface (without killing them). Alternatively, polymers with antimicrobial agents such as quaternary ammonium compounds, guanides, phosphonium salts, or antibiotics are proven to kill bacteria on contact.

There are number of different approaches to couple antimicrobial agents to polymers. Among these approaches, covalent attachment of bioactive molecules onto polymer backbone offers better stability and uniformity compared to surface physisorption methods. Various synthetic routes have been developed for covalent bonding of species onto surfaces such as grafting to and grafting from techniques. Polymer brushes, random or block copolymers prepared with these methods result in a long term stability with a broad range of chemical functionalities.

This review gives an overview of antifouling and antimicrobial polymers with the focus on biopassive and covalently immobilized bioactive surface preparations. Biopassive surface coatings reduce the adsorption of proteins and thus the adhesion of bacteria, typically through the incorporation of hydrophilic well-hydrated polymers that are either covalently immobilized or physisorbed on the surface. Conversely, the bioactive polymers discussed within this review can kill the bacteria on contact through the immobilization of antibiotics and antimicrobial agents. Surface coatings that incorporate a bioactive moiety that is released into the vinicity of the surface are beyond the scope of this review, but have been extensively reviewed elsewhere [6], [7], [8].