Polymer–Nanoparticle Interaction as a Design Principle in the Development of a Durable Ultrathin Universal Binary Antibiofilm Coating with Long-Term Activity

Abstract

Bacterial attachment and biofilm formation pose major challenges to the optimal performance of indwelling devices. Current coating methods have significant deficiencies including the lack of long-term activity, easy of application, and adaptability to diverse materials. Here we describe a coating method that could potentially overcome such limitations and yield an ultrathin coating with long-term antibiofilm activity. We utilized the interaction between polydopamine (PDA) nanoaggregates/nanoparticles and ultrahigh molecular weight (uHMW) hydrophilic polymers to generate stable coatings with broad spectrum antibiofilm activity. We used a short-term bacterial adhesion assay as an initial screening method to identify coating compositions that give superior performance and found that only selected polymers (out of 13 different types) and molecular weights gave promising antifouling activity. Optimization of PDA self-assembly, polymer− PDA interaction, and deposition on the surface using uHMW poly(N,N-dimethylacrylamide) (PDMA) (∼795 kDa) resulted in a stable ultrathin coating (∼19 nm) with excellent antifouling and antibiofilm properties (>4 weeks) against diverse bacteria (∼10 8 CFU/mL) in shaking and flow conditions. The ultrathin coating is effective on diverse substrates including metals and polymeric substrates. The uHMW PDMA is stabilized in the coating via supramolecular interactions with PDA and generated a surface that is highly enriched with PDMA in aqueous conditions. Based on the surface analyses data, we also propose a mechanism for the stable coating formation. The molecular weight of PDMA is a crucial factor, and only uHMW polymers generate this property. An attractive feature of the coating is that it does not contain any antimicrobial agents and has the potential to prevent biofilm formation for diverse applications both short-and long-term.

Self‐Limiting Mussel Inspired Thin Antifouling Coating with Broad‐Spectrum Resistance to Biofilm Formation to Prevent Catheter‐Associated Infection in Mouse and Porcine Models

“…The molecular weight of PDMA was crucial to form a coating with strong antibiofilm activity. The PDMA with ultrahigh molecular weight exhibits its unique characteristics as it can control the self‐assembly of polydopamine (PDA) nano‐aggregates [ 27 ] formed during the polymerization of dopamine and resulted in a stable, thin, and uniform coating with PDMA chains enriched on the surface of diverse substrates irrespective of their surface chemistry or morphology (Figure 1A).…”

“…We have previously developed a water‐based, simple one‐step dip coating approach based on mussel‐inspired chemistry and coassembly with hydrophilic ultrahigh molecular weight poly( N,N ‐dimethylacrylamide) (uhPDMA) under ambient conditions. [ 27 ] It was found that the polymer chemistry and molecular weight of hydrophilic polymer is crucial to form an antifouling coating against bacterial adhesion over the long term. In this study, we investigated the mechanism of formation, performed extensive surface characterization of the coating, applied the self‐limiting thin antiadhesive coating on diverse clinically used catheter materials of different interfacial properties, and the scalability of the coating process to human‐sized catheters.…”

Surface Modification by Nano-Structures Reduces Viable Bacterial Biofilm in Aerobic and Anaerobic Environments

“…The former mainly employs surface modifications, bactericidal coatings or anti-adhesive compounds as physical barriers [ 9 , 10 ], and the latter involves antimicrobial agents that kill or inhibit the growth of microorganisms [ 11 ]. Despite the advancements in the development of antimicrobial and anti-biofilm materials, coating techniques bear significant deficiencies, including the lack of long-term activity and stability, lack of coating adaptability to diverse materials, easy production and simple application [ 12 ].…”

“…Depending on the specific building blocks and the assembly conditions, various nano-structured morphologies, including fibrils, tubes, sheets, tapes, spheres, vesicles and hydrogel matrices, can be formed in vitro, allowing for distinctive functional possibilities [ 28 , 30 , 31 , 32 , 33 , 34 , 35 ], mainly in tissue engineering [ 36 , 37 , 38 , 39 ], regenerative medicine [ 40 ], cell culture [ 41 , 42 , 43 , 44 ], drug delivery [ 36 , 39 , 45 , 46 , 47 , 48 , 49 ], bio-imaging [ 50 , 51 ] and fabric functionalization [ 52 ]. Coatings based on self-assembled peptides, primarily for antibacterial purposes, have been recently reported [ 5 , 12 , 13 , 21 , 53 , 54 , 55 , 56 ]. The self-assembly of the tri-peptide DOPA-Phe(4F)-Phe(4F)-OMe into an antifouling coating by the dip-coating technique was reported [ 13 ].…”

“…The peptide-based coating has been shown to successfully inhibit Pseudomonas aeruginosa and Escherichia coli biofilm formation on titanium surfaces and was found to be biocompatible [ 13 , 56 ]. In another study, the combination of self-assembled polydopamine nano-aggregates with an ultrahigh molecular weight hydrophilic polymer had been utilized as a broad-spectrum antibacterial coating of titanium and polymeric surfaces [ 12 ]. Other studies utilized peptide self-assembly into coatings to improve cell attachment and proliferation [ 54 , 55 ].…”