Long-Term Prevention of Biofilm Formation by Polycatechol-Based Supramolecular Assemblies with Low Molecular Weight Polymers on Surfaces.

Achievement of a stable surface coating with long-term resistance to biofilm formation remains a challenge. Catechol-based polymerization chemistry and surface deposition are used as tools for surface modification of diverse materials. However, the control of surface deposition of the coating, surface coverage, coating properties, and long-term protection against biofilm formation remain to be solved. We report a new approach based on supramolecular assembly to generate long-acting antibiofilm coating. Here, we utilized catechol chemistry in combination with low molecular weight amphiphilic polymers for the generation of such coatings. Screening studies with diverse low molecular weight (LMW) polymers and different catechols are utilized to identify lead compositions, which resulted in a thick coating with high surface coverage, smoothness, and antibiofilm activity. We have identified that small supramolecular assemblies (∼10 nm) formed from a combination of polydopamine and LMW poly(N-vinyl caprolactam) (PVCL) resulted in relatively thick coating (∼300 nm) with excellent surface coverage in comparison to other polymers and catechol combinations. The coating properties, such as thickness (10-300 nm) and surface hydrophilicity (with water contact angle: 20-60°), are readily controlled. The optimal coating composition showed excellent antibiofilm properties with long-term (>28 days) antibiofilm activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains. We further utilized the combination of optimal binary coating with silver to generate a coating with sustained release of silver ions, resulting in killing both adhered and planktonic bacteria and preventing long-term surface bacterial colonization. The new coating method utilizing LMW polymers opens a new avenue for the development of a novel class of thick, long-acting antibiofilm coatings.

Robust Nanoparticle-Derived Lubricious Antibiofilm Coating for Difficult-to-Coat Medical Devices with Intricate Geometry.

A major medical device-associated complication is the biofilm-related infection post-implantation. One promising approach to prevent this is to coat already commercialized medical devices with effective antibiofilm materials. However, developing a robust high-performance antibiofilm coating on devices with a nonflat geometry remains unmet. Here, we report the development of a facile scalable nanoparticle-based antibiofilm silver composite coating with long-term activity applicable to virtually any objects including difficult-to-coat commercially available medical devices utilizing a catecholic organic-aqueous mixture. Using a screening approach, we have identified a combination of the organic-aqueous buffer mixture which alters polycatecholamine synthesis, nanoparticle formation, and stabilization, resulting in controlled deposition of in situ formed composite silver nanoparticles in the presence of an ultra-high-molecular-weight hydrophilic polymer on diverse objects irrespective of its geometry and chemistry. Methanol-mediated synthesis of polymer-silver composite nanoparticles resulted in a biocompatible lubricious coating with high mechanical durability, long-term silver release (∼90 days), complete inhibition of bacterial adhesion, and excellent killing activity against a diverse range of bacteria over the long term. Coated catheters retained their excellent activity even after exposure to harsh mechanical challenges (rubbing, twisting, and stretching) and storage conditions (>3 months stirring in water). We confirmed its excellent bacteria-killing efficacy (>99.999%) against difficult-to-kill bacteria (Proteus mirabilis) and high biocompatibility using percutaneous catheter infection mice and subcutaneous implant rat models, respectively, in vivo. The developed coating approach opens a new avenue to transform clinically used medical devices (e.g., urinary catheters) to highly infection-resistant devices to prevent and treat implant/device-associated infections.

Antibacterial and Antiviral Coating on Surfaces through Dopamine-Assisted Codeposition of an Antifouling Polymer and In Situ Formed Nanosilver.

Bacteria and viruses can adhere onto diverse surfaces and be transmitted in multiple ways. A bifunctional coating that integrates both antibacterial and antiviral activities is a promising approach to mitigate bacterial and viral infections arising from a contaminated surface. However, current coating approaches encounter a slow reaction, limited activity against diverse bacteria or viruses, short-term activity, difficulty in scaling-up, and poor adaptation to diverse material surfaces. Here, we report a new one-step strategy for the development of a polydopamine-based nonfouling antibacterial and antiviral coating by the codeposition of various components. The in situ formed nanosilver in the presence of polydopamine was incorporated into the coating and served as both antibacterial and antiviral agents. In addition, the coassembly of polydopamine and a nonfouling hydrophilic polymer was constructed to prevent the adhesion of bacteria and viruses on the coating. The coating was prepared on model surfaces and thoroughly characterized using various surface analytical techniques. The coating exhibited strong antifouling properties with a reduction of nonspecific protein adsorption up to 90%. The coating was tested against both Gram-positive and Gram-negative bacteria and showed long-term antibacterial effectiveness, which correlated with the composition of the coating. The antiviral activity of the coating was evaluated against human coronavirus 229E. A possible mechanism of action of the coating was proposed. We anticipate that the optimized coating will have applications in the development of infection prevention devices and surfaces.

Hydrophilic Polymer-Guided Polycatecholamine Assembly and Surface Deposition.

Mussel-inspired surface chemistry based on polycatecholamines and polyphenols has been widely applied as a facile and universal method for modifying surfaces. Specifically, the catecholamine-assisted codeposition as a one-step strategy is a versatile strategy used to impart surface functionalities. Despite successful incorporation of numerous functional agents, very little understanding has emerged over the years regarding the mechanism behind their coassembly and codeposition. Here, we employed six different ultrahigh molecular weight hydrophilic polymers of diverse chemistry and architecture and three catecholamines and a polyphenol for investigating the coassembly and codeposition process. The chemistry of the polymers is found to influence the strength of the interaction between the polycatecholamine and the hydrophilic polymers, thus playing an important role in the aqueous self-assembly in solution to nanoaggregates, its formation kinetics, steric stabilization, and surface deposition. Additionally, the codeposition method was used as a platform for developing antifouling and antibiofilm coatings and evaluating their efficiency. Both the chemistry of hydrophilic polymers and the type of the catecholamine influence the antibiofilm properties of the coating. Our studies demonstrated that significant opportunities exist to further define the surface coating process and polycatecholamine self-assembly process by altering the polycatecholamine-hydrophilic polymer interactions.

Durable Surfaces from Film-Forming Silver Assemblies for Long-Term Zero Bacterial Adhesion without Toxicity.

The long-term prevention of biofilm formation on the surface of indwelling medical devices remains a challenge. Silver has been reutilized in recent years for combating biofilm formation due to its indisputable bactericidal potency; however, the toxicity, low stability, and short-term activity of the current silver coatings have limited their use. Here, we report the development of silver-based film-forming antibacterial engineered (SAFE) assemblies for the generation of durable lubricous antibiofilm surface long-term activity without silver toxicity that was applicable to diverse materials via a highly scalable dip/spray/solution-skinning process. The SAFE coating was obtained through a large-scale screening, resulting in effective incorporation of silver nanoparticles (∼10 nm) into a stable nonsticky coating with high surface hierarchy and coverage, which guaranteed sustained silver release. The lead coating showed zero bacterial adhesion over a 1 month experiment in the presence of a high load of diverse bacteria, including difficult-to-kill and stone-forming strains. The SAFE coating showed high biocompatibility and excellent antibiofilm activity in vivo.

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

Catheter-associated urinary tract infections (CAUTIs) are one of the most commonly occurring hospital-acquired infections. Current coating strategies to prevent catheter-associated biofilm formation are limited by their poor long-term efficiency and limited applicability to diverse materials. Here, the authors report a highly effective non-fouling coating with long-term biofilm prevention activity and is applicable to diverse catheters. The thin coating is lubricous, stable, highly uniform, and shows broad spectrum prevention of biofilm formation of nine different bacterial strains and prevents the migration of bacteria on catheter surface. The coating method is adapted to human-sized catheters (both intraluminal and extraluminal) and demonstrates long-term biofilm prevention activity over 30 days in challenging conditions. The coated catheters are tested in a mouse CAUTI model and demonstrate high efficiency in preventing bacterial colonization of both Gram-positive and Gram-negative bacteria. Furthermore, the coated human-sized Foley catheters are evaluated in a porcine CAUTI model and show consistent efficiency in reducing biofilm formation by Escherichia coli (E. coli) over 95%. The simplicity of the coating method, the ability to apply this coating on diverse materials, and the high efficiency in preventing bacterial adhesion increase the potential of this method for the development of next generation infection resistant medical devices.

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

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 (∼108 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.