Facile synthesis and coating of aqueous antifouling polymers for inhibiting pathogenic bacterial adhesion on medical devices

Highlights

• APs prevents pathogenic bacterial adhesion on polymeric medical devices.

• Optimized APs could be synthesized on the surfaces of commercial hydrophobic.

• AP has no significant cytotoxicity.

Abstract

Bacterial colonization in the form of biofilms on surfaces causes persistent infections and is an issue of considerable concern to healthcare providers. Thus, there is an urgent need for novel modification of antibiofilm surfaces on polymeric medical devices to inhibit pathogenic bacterial adhesion. Herein, we describe the development of water-soluble, antifouling polymers (APs) containing benzene moieties capable of anchoring to hydrophobic surfaces and hydrophilic poly (ethylene) glycol and carboxyl groups to inhibit pathogenic bacterial adhesion on polymeric medical devices. We found that the optimized APs could be facilely and controllably synthesized on and modify the surfaces of commercial hydrophobic substrates in aqueous solution, with the resulting polymer-coated surfaces capable of efficiently preventing pathogenic bacterial adhesion and subsequent bacterial colonization as precursors to biofilm formation. These results suggest the potential efficacy of the developed and optimized polymers for use as an antibiofilm platform to inhibit healthcare-associated infections on various polymer-based medical devices.

Introduction

Biofilms are a microscopic community of cells attached to a substrate and that secrete extracellular polymeric substances (EPS) to protect organized colonies from hostile factors, such as host immune cells and antibacterial agents [1]. Generally, microbes are capable of adhering to surfaces, including those of inert materials and implantable medical devices, to promote colonization and the formation of mature biofilm, which play a pivotal role in healthcare-associated infections (HAIs) and present a serious concern as a life-threatening complication for patients [2]. Therefore, prevention of microbial biofilm formation on the surface of medical devices is a technological imperative in healthcare.

Biofilm formation by bacterial adhesion or nonspecific adsorption of unwanted proteins depends on the hydrophobicity of the surface material on polymeric medical devices [1,3,4]. The majority of medical devices are created using durable, hydrophobic, polymer-based materials, such as polyurethane, silicone rubber, and poly (methyl methacrylate) (PMMA) [4,5]. A critical problem with polymer-based materials is their propensity to allow biofilm formation under pristine conditions, as their surfaces are rapidly fouled and coated with biological fluids, such as plasma proteins that facilitate bacterial attachment [2,5,6]. Following bacterial adherence to and subsequent colonization of a hydrophobic polymer surface, it is difficult to stop the subsequent formation of biofilm [3,7]. To address these issues, potential antibiofouling and antibiofilm strategies were recently developed to prevent initial bacterial adhesion and inhibit biofilm maturation. One common approach involves treating or incorporating surfaces with biocides, such as metal ions, chemical agents (chlorhexidine, triclosan, or quaternary ammonium salts), or metal nanoparticles (cooper, silver, or mercury) [6,[8], [9], [10]]; however, these approaches are limited by their short lifetime and toxicity [[11], [12], [13]]. Other efforts to intervene during the initial phase of bacterial adhesion involved coating the surface with an antibiofilm polymer [11,12,14,15]. Reductions in protein adsorption by and bacterial adhesion to a material surface can be achieved by the grafting hydrophilic polymers, such as polyethylene glycol (PEG). The advantages of using PEG include its low interfacial free energy, lack of binding sites, highly dynamic motion, and extended-chain conformation on the hydrophobic surface [16,17].

We previously reported that an amphiphilic, antibiofouling polymer synthesized from a hydrophobic chain benzyl methacrylate (BMA), PEG methacrylate (PEGMA), and a methacrylic acid (MA) [designated as poly(BMA-r-mPEGMA-r-MA)] could effectively coat the surfaces of hydrophobic materials, such as polystyrene (PS) and cyclic olefin copolymer substrates [19,20]. The resulting polymer-coated surfaces effectively prevented the nonspecific adsorption of unwanted proteins; however, we did not investigate the potential antibiofilm capacity of the optimized polymer. Therefore, there is a need for a new antibiofilm coating material that enables efficient and sustainable blockage of bacterial adhesion through a facile and controllable manufacturing process in aqueous solutions in order to avoid concerns related to the use of hazardous chemicals [4,18]. In the present study, we describe the development and optimization of water-soluble, antifouling polymers (APs) containing hydrophobic benzene moieties and hydrophilic PEG and carboxyl (COOH) groups capable of inhibiting pathogenic bacterial adhesion on polymeric medical devices [19,20]. We found that the optimized APs underwent facile and controllable synthesis and coated the surfaces of commercial hydrophobic materials in water, with the resulting polymer-coated surfaces capable of efficiently preventing pathogenic bacterial adhesion and subsequent bacterial colonization and biofilm formation. Furthermore, we evaluated the biocompatibility of the APs and polymer-coated materials for various biomedical applications.