Normally Oriented Adhesion versus Friction Forces in Bacterial Adhesion to Polymer‐Brush Functionalized Surfaces Under Fluid Flow

Bacterial adhesion is problematic in many diverse applications. Coatings of hydrophilic polymer chains in a brush configuration reduce bacterial adhesion by orders of magnitude, but not to zero. Here, the mechanism by which polymer‐brush functionalized surfaces reduce bacterial adhesion from a flowing carrier fluid by relating bacterial adhesion with normally oriented adhesion and friction forces on polymer (PEG)‐brush coatings of different softness is studied. Softer brush coatings deform more than rigid ones, which yields extensive bond‐maturation and strong, normally oriented adhesion forces, accompanied by irreversible adhesion of bacteria. On rigid brushes, normally oriented adhesion forces remain small, allowing desorption and accordingly lower numbers of adhering bacteria result. Friction forces, generated by fluid flow and normally oriented adhesion forces, are required to oppose fluid shear forces and cause immobile adhesion. Summarizing, inclusion of friction forces and substratum softness provides a more complete mechanism of bacterial adhesion from flowing carrier fluids than available hitherto.     

Surfactant‐Free One‐Step Synthesis of Dual‐Functional Polyurea Microcapsules: Contact Infection Control and Drug Delivery

Surface functionalized polyurea microcapsules (MCQ) are synthesized in one step. Dimethyl‐dodecyl‐(5‐hydroxy‐pentyl)‐ammonium bromide (DAB), a hydroxyl‐end‐capped quaternary ammonium salt, is synthesized and adopted as a new surfmer for the synthesis of MCQ. It is confirmed by fluorescein adsorption that DAB is covalently bonded to MCQ. The so‐formed MCQ possess dual‐functionality: contact infection control and sustained drug delivery. Agar diffusion antimicrobial tests confirm successful inhibition of multi‐drug‐resistant E. coli by MCQ alone instead of by leaching of free quaternary ammonium salts. Furthermore, few E. coli colonies survive on an agar plate coated with 3–4 layers of MCQ. Dissolution tests show a typical first‐order release profile of courmarin‐1, a model dye, from MCQ.     

Photoresponsive Sponge‐Like Coating for On‐Demand Liquid Release

Many publications report on stimuli responsive coatings, but only a few on the controlled release of species in order to change the coating surface properties. A sponge‐like coating that is able to release and absorb a liquid upon exposure to light has been developed. The morphology of the porous coating is controlled by the smectic liquid crystal properties of the monomer mixture prior to its polymerization, and homeotropic order is found to give the largest contraction. The fast release of the liquid can be induced by a macroscopic contraction of the coating caused by a trans to cis conversion of a copolymerized azobenzene moiety. The liquid secretion can be localized by local light exposure or by creating a surface relief. The uptake of liquid proceeds by stimulating the back reaction of the azo compound by exposure at higher wavelength or by thermal relaxation. The surface forces of the sponge‐like coating in contact with an opposing surface can be controlled by light‐induced capillary bridging revealing that the controlled release of liquid gives access to tunable adhesion.     

A Coating that Combines Lotus‐Effect and Contact‐Active Antimicrobial Properties on Silicone

The antimicrobial equipment of materials is of great importance in medicine but also in daily life. A challenge is the antimicrobial modification of hydrophobic surfaces without increasing their low surface energy. This is particularly important for silicone‐based materials. Because most antimicrobial surface modifications render the materials more hydrophilic, methods are needed to achieve antimicrobial activity without changing the high water‐contact‐angle. This is achieved in the present work, where SiO₂ nanoparticles are prepared and functionalized with 3‐(trimethoxysilyl)‐propyldimethyloctadecyl ammonium chloride (QAS) in a one‐pot synthesis. The modified nanoparticles are applied onto a silicone surface from suspension with no need of elaborate pretreatment. The resulting surface exhibits a Lotus‐Effect combined with contact‐active antimicrobial properties. The particle surfaces show self‐organizing micro‐ and nanostructures that afford a water‐contact angle of 144° and a hysteresis below 10°. The particles are self‐adhering on the silicone after solvent evaporation and resistant against immersion into and washing with water for at least 5 d. Thereby, the adhesion of the bacterial strain Staphylococcus aureus to these surfaces is reduced and the remaining bacterial cells are killed within 16 h. This is the first example of a Lotus‐Effect surface with intrinsic contact‐active antimicrobial properties.     

3D‐Printable Antimicrobial Composite Resins

3D printing is seen as a game‐changing manufacturing process in many domains, including general medicine and dentistry, but the integration of more complex functions into 3D‐printed materials remains lacking. Here, it is expanded on the repertoire of 3D‐printable materials to include antimicrobial polymer resins, which are essential for development of medical devices due to the high incidence of biomaterial‐associated infections. Monomers containing antimicrobial, positively charged quaternary ammonium groups with an appended alkyl chain are either directly copolymerized with conventional diurethanedimethacrylate/glycerol dimethacrylate (UDMA/GDMA) resin components by photocuring or prepolymerized as a linear chain for incorporation into a semi‐interpenetrating polymer network by light‐induced polymerization. For both strategies, dental 3D‐printed objects fabricated by a stereolithography process kill bacteria on contact when positively charged quaternary ammonium groups are incorporated into the photocurable UDMA/GDMA resins. Leaching of quaternary ammonium monomers copolymerized with UDMA/GDMA resins is limited and without biological consequences within 4–6 d, while biological consequences could be confined to 1 d when prepolymerized quaternary ammonium group containing chains are incorporated in a semi‐interpenetrating polymer network. Routine clinical handling and mechanical properties of the pristine polymer matrix are maintained upon incorporation of quaternary ammonium groups, qualifying the antimicrobially functionalized, 3D‐printable composite resins for clinical use.     

Polymer‐Based Porous Microcapsules as Bacterial Traps

Exposure to live bacteria and accumulation of dead bacteria during bactericidal processes can cause bacterial infectious diseases, implant failure, and antibacterial surface deterioration. Microcapsules with asymmetrically distributed, funnel‐shaped pores, which are capable of capturing, retaining, and killing bacteria are developed, offering a solution to bacterial contamination in liquids. It is found that bacterial isolation inside microcapsules is mainly driven by the bacteria's own motility and the microcapsules' geometry. After entry into the microcapsule cavity, the bacteria are stably retained inside. The microcapsules shield surrounding cells from exposure to bacterial toxins, as demonstrated by the coculture of rat embryonic fibroblast cells with microcapsules loaded with live Escherichia coli. The microcapsules can be enhanced with a bactericidal coating covering only the interior cavity. This confines the bacteria‐killing process, thereby further increasing biocompatibility. The microcapsules may offer a viable bacteria combatant approach as a potentially advantageous method to eradicate bacterial contamination.     

Polycationic Synergistic Antibacterial Agents with Multiple Functional Components for Efficient Anti‐Infective Therapy

Multifunctional antibacterial photodynamic therapy is a promising method to combat regular and multidrug‐resistant bacteria. In this work, eosin Y (EY)‐based antibacterial polycations (EY‐QEGED? R, R = ? CH₃ or ? C₆H₁₃) with versatile types of functional components including quaternary ammonium, photosensitizer, primary amine, and hydroxyl species are readily synthesized based on simple ring‐opening reactions. In the presence of light irradiation, such antibacterial polymers exhibit high antibacterial efficiency against both Escherichia coli and Staphylococcus aureus. In particular, EY‐QEGED? R elicits a remarkable synergistic antibacterial activity owing to the combined photodynamic and quaternary ammonium antibacterial effects. Due to its rich primary amine groups, EY‐QEGED? R also can be readily coated on different substrates, such as glass slides and nonwoven fabrics via an adhesive layer of polydopamine. The resultant surface coating of EY‐QEGED? CH₃ (s‐EY‐QEGED? CH₃) produces excellent in vitro antibacterial efficacy. The plentiful hydroxyl groups impart s‐EY‐QEGED? CH₃ with potential antifouling capability against dead bacteria. The antibacterial polymer coatings also demonstrate low cytotoxicity and good hemocompatibility. More importantly, s‐EY‐QEGED? CH₃ significantly enhances in vivo therapeutic effects on an infected rat model. The present work provides an efficient strategy for the rational design of high‐performance antibacterial materials to fight biomedical device‐associated infections.     

Protein‐Enabled Layer‐by‐Layer Syntheses of Aligned,Porous‐Wall,High‐Aspect‐Ratio TiO2 Nanotube Arrays

An aqueous, protein‐enabled (biomimetic), layer‐by‐layer titania deposition process is developed, for the first time, to convert aligned‐nanochannel templates into high‐aspect‐ratio, aligned nanotube arrays with thin (34 nm) walls composed of co‐continuous networks of pores and titania nanocrystals (15 nm ave. size). Alumina templates with aligned open nanochannels are exposed in an alternating fashion to aqueous protamine‐bearing and titania precursor‐bearing (Ti(IV) bis‐ammonium‐lactato‐dihydroxide, TiBALDH) solutions. The ability of protamine to bind to alumina and titania, and to induce the formation of a Ti–O‐bearing coating upon exposure to the TiBALDH precursor, enables the layer‐by‐layer deposition of a conformal protamine/Ti–O‐bearing coating on the nanochannel surfaces within the porous alumina template. Subsequent protamine pyrolysis yields coatings composed of co‐continuous networks of pores and titania nanoparticles. Selective dissolution of the underlying alumina template through the porous coating then yields freestanding, aligned, porous‐wall titania nanotube arrays. The interconnected pores within the nanotube walls allow enhanced loading of functional molecules (such as a Ru‐based N719 dye), whereas the interconnected titania nanoparticles enable the high‐aspect‐ratio, aligned nanotube arrays to be used as electrodes (as demonstrated for dye‐sensitized solar cells with power conversion efficiencies of 5.2 ± 0.4%).     

Bacterium‐Templated Polymer for Self‐Selective Ablation of Multidrug‐Resistant Bacteria

The recognition and inactivation of specific pathogenic bacteria remain an enormous scientific challenge and an important therapeutic goal. Therefore, materials that can selectively target and kill specific pathogenic bacteria, without harming beneficial strains are highly desirable. Here, a material platform is reported that exploits bacteria as a template to synthesize polymers with aggregation‐induced emission (AIE) characteristic by copper‐catalyzed atom transfer radical polymerization for self‐selective killing of the bacteria that templates them with no antimicrobial resistance. The bacteria‐templated polymers show very weak fluorescence in aqueous media, however, the fluorescence is turned on upon recognition of the bacteria used as the template to synthesize the polymer even at a low concentration of 600 ng mL^?1. Moreover, the incorporated AIE fluorogens (AIEgens) can act as an efficient photosensitizer for reactive oxygen species (ROS) generation after bacteria surface binding, which endows the templated polymers with the capability for selective bacterial killing. The bacterium‐templated synthesis is generally applicable to a wide range of bacteria, including clinically isolated multidrug‐resistant bacterial strains. It is envisioned that the bacterium‐templated method provides a new strategy for bacteria‐specific diagnostic and therapeutic applications.     

Biodegradable Supramolecular Materials Based on Cationic Polyaspartamides and Pillar[5]arene for Targeting Gram‐Positive Bacteria and Mitigating Antimicrobial Resistance

The increasing number of infections caused by pathogenic bacteria has severely affected human society, for instance, numerous deaths are from Gram‐positive methicillin‐resistant Staphylococcus aureus (MRSA) each year. In this work, four biodegradable antibacterial polymer materials based on cationic polyaspartamide derivatives with different lengths of side chains are synthesized through the ring‐opening polymerization of β‐benzyl‐l ‐aspartate N‐carboxy anhydride, followed by an aminolysis reaction and subsequent methylation reaction. The cationic quaternary ammonium groups contribute to the insertion of the catiomers into the negatively charged bacterial membranes, which leads to membranolysis, the leakage of bacterial content, and the death of pathogens. Except for wiping out MRSA readily, the biodegradable polymers possessing alterable antibacterial potency can minimize the possibility of microbial resistance and mitigate drug accumulation by virtue of their cleavable backbone. To manipulate the poor biocompatibility of these polycations, carboxylatopillar[5]arene (CP[5]A) is introduced to the polymeric antibacterial catiomers through the supramolecular host–guest approach to obtain novel antibacterial materials with pH‐sensitive characteristics (with CP[5]A departure from cationic quaternary ammonium compounds under acid conditions) and selective targeting of Gram‐positive bacteria. Finally, the facile and robust antibacterial system is successfully applied to in vivo MRSA‐infected wound healing, providing a significant reference for the construction of advanced antibacterial biomaterials.     

Contact‐Killing Polyelectrolyte Microcapsules Based on Chitosan Derivatives

Polyelectrolyte‐multilayer microcapsules are made by layer‐by‐layer (LbL) assembly of oppositely charged polyelectrolytes onto sacrificial colloidal particles, followed by core removal. In this paper, contact‐killing polyelectrolyte microcapsules are prepared based solely on polysaccharides. To this end, water‐soluble quaternized chitosan (QCHI) with varying degrees of substitution (DS) and hyaluronic acid (HA) are assembled into thin films. The quaternary ammonium groups are selectively grafted on the primary amine group of chitosan by exploiting its reaction with glycidyltrimethylammonium chloride (GTMAC) under homogeneous aqueous acidic conditions. The morphology of the capsules is closely dependent on the DS of the quaternized chitosan derivatives, which suggests differences in their complexation with HA. The DS is also a key parameter to control the antibacterial activity of QCHI against Escherichia Coli (E. coli). Thus, capsules containing the QCHI derivative with the highest DS are shown to be the most efficient to kill E. coli while retaining their biocompatibility toward myoblast cells, which suggests their potential as drug carriers able to combat bacterial infections.     

Titania Nanotubes: Protein‐Enabled Layer‐by‐Layer Syntheses of Aligned,Porous‐Wall,High‐Aspect‐Ratio TiO2 Nanotube Arrays (Adv. Funct. Mater. 9/2011)

An aqueous, protein‐enabled (biomimetic), layer‐by‐layer titania deposition process is developed, for the first time, to convert aligned‐nanochannel templates into high‐aspect‐ratio, aligned nanotube arrays with thin (34 nm) walls composed of co‐continuous networks of pores and titania nanocrystals (15 nm ave. size). Alumina templates with aligned open nanochannels are exposed in an alternating fashion to aqueous protamine‐bearing and titania precursor‐bearing (Ti(IV) bis‐ammonium‐lactato‐dihydroxide, TiBALDH) solutions. The ability of protamine to bind to alumina and titania, and to induce the formation of a Ti–O‐bearing coating upon exposure to the TiBALDH precursor, enables the layer‐by‐layer deposition of a conformal protamine/Ti–O‐bearing coating on the nanochannel surfaces within the porous alumina template. Subsequent protamine pyrolysis yields coatings composed of co‐continuous networks of pores and titania nanoparticles. Selective dissolution of the underlying alumina template through the porous coating then yields freestanding, aligned, porous‐wall titania nanotube arrays. The interconnected pores within the nanotube walls allow enhanced loading of functional molecules (such as a Ru‐based N719 dye), whereas the interconnected titania nanoparticles enable the high‐aspect‐ratio, aligned nanotube arrays to be used as electrodes (as demonstrated for dye‐sensitized solar cells with power conversion efficiencies of 5.2 ± 0.4%).     

Hydrophilic and Antimicrobial Zeolite Coatings for Gravity‐Independent Water Separation

Condensing heat exchangers onboard manned spacecraft require hydrophilic fin surfaces to facilitate wetting and wicking of condensate to achieve gravity‐independent water separation in the zero‐ or micro‐gravity environment of space. In order to prevent the proliferation of microbes, the coating must also be biocidal. Here we show for the first time that zeolite A and ZSM‐5 coatings deposited via in‐situ crystallization on stainless steel and aluminum alloys have excellent hydrophilicity, biocidal properties, and adhesion. Water contact angles below 5° were obtained on most substrates tested. When silver‐ion exchange is carried out on the zeolite A coating, it becomes highly antibacterial. This biocidal capability of zeolite A is regenerative by repeated ion exchange. All coatings exhibit the highest rating of 5B as determined by adhesion test ASTM D‐3359‐02 (American Society for Testing and Materials). These properties, in addition to zeolite coating's low‐temperature crystallization process and demonstrated corrosion resistance, make zeolite coatings advantageous over the current sol–gel coatings and well suited for use in condensing heat exchangers onboard manned spacecraft.     

A Functional DNase I Coating to Prevent Adhesion of Bacteria and the Formation of Biofilm

Biofilms are detrimental in many industrial and biomedical applications and prevention of biofilm formation has been a prime challenge for decades. Biofilms consist of communities of adhering bacteria, supported and protected by extracellular‐polymeric‐substances (EPS), the so‐called “house of biofilm organisms”. EPS consists of water, proteins, polysaccharides and extracellular‐DNA (eDNA). eDNA, being the longest molecule in EPS, connects the different EPS components and therewith holds an adhering biofilm together. eDNA is associated with bacterial cell surfaces by specific and non‐specific mechanisms, mediating binding of other biopolymers in EPS. eDNA therewith assists in facilitating adhesion, aggregation and maintenance of biofilm structure. Here, a new method is described to prevent biofilm formation on surfaces by applying a DNase I enzyme coating to polymethylmethacrylate, using dopamine as an intermediate. The intermediate coupling layer and final DNase I coating are characterized by water‐contact‐angle measurements and X‐ray photoelectron‐spectroscopy. The DNase I coating strongly reduces adhesion of Staphylococcus aureus (95%) and Pseudomonas aeruginosa (99%) and prevents biofilm formation up to 14 h, without affecting mammalian cell adhesion and proliferation. Also agarose‐gel‐electrophoresis indicates loss of enzyme activity between 8 and 24 h. This duration however, is similar to many local antibiotic‐delivery devices, which makes it an ideal coating for biomaterial implants and devices, known to fail due to biofilm formation with disastrous consequences for patients and high costs to the healthcare system. With threatening increases in antibiotic resistance, the DNase I coating may provide a timely, potent new approach to biofilm prevention on biomaterial implants and devices.     

Copper‐Based Nanostructured Coatings on Natural Cellulose: Nanocomposites Exhibiting Rapid and Efficient Inhibition of a Multi‐Drug Resistant Wound Pathogen,A. baumannii,and Mammalian Cell Biocompatibility In Vitro

This paper describes a layer‐by‐layer (LBL) electrostatic self‐assembly process for fabricating highly efficient antimicrobial nanocoatings on a natural cellulose substrate. The composite materials comprise a chemically modified cotton substrate and a layer of sub‐5 nm copper‐based nanoparticles. The LBL process involves a chemical preconditioning step to impart high negative surface charge on the cotton substrate for chelation controlled binding of cupric ions (Cu²⁺), followed by chemical reduction to yield nanostructured coatings on cotton fibers. These model wound dressings exhibit rapid and efficient killing of a multidrug resistant bacterial wound pathogen, A. baumannii, where an 8‐log reduction in bacterial growth can be achieved in as little as 10 min of contact. Comparative silver‐based nanocoated wound dressings–a more conventional antimicrobial composite material–exhibit much lower antimicrobial efficiencies; a 5‐log reduction in A. baumannii growth is possible after 24 h exposure times to silver nanoparticle‐coated cotton substrates. The copper nanoparticle–cotton composites described herein also resist leaching of copper species in the presence of buffer, and exhibit an order of magnitude higher killing efficiency using 20 times less total metal when compared to tests using soluble Cu²⁺. Together these data suggest that copper‐based nanoparticle‐coated cotton materials have facile antimicrobial properties in the presence of A. baumannii through a process that may be associated with contact killing, and not simply due to enhanced release of metal ion. The biocompatibility of these copper‐cotton composites toward embryonic fibroblast stem cells in vitro suggests their potential as a new paradigm in metal‐based wound care and combating pathogenic bacterial infections.     

Nonchemotherapic and Robust Dual‐Responsive Nanoagents with On‐Demand Bacterial Trapping,Ablation, and Release for Efficient Wound Disinfection

Recent emerged antibacterial agents provide enormous new possibilities to replace antibiotics in fighting bacterial infectious diseases. Although abundant types of nanoagents are developed for preventing pathogen colonization, however, rationally design of nonchemotherapic, robust, and clinical‐adaptable nanoagents with tunable bacterial trap and killing activities remains a major challenge. Here, a demonstration of controlling the trap, ablation, and release activities of pathogenic bacteria via stimulus‐responsive regulatory mechanism is reported. First, temperature‐sensitive polymer brush is chemically grown onto carbon nanotube–Fe₃O₄, whereby the synthesized nanoagents can transfer from hydrophilic dispersion to hydrophobic aggregation upon near‐infrared light irradiation, which thus controls the bacterial trap, killing, and detaching. In turn, the formed aggregations will serve as localized heating sources to enhance photothermal ablation of bacteria. Systematically antibacterial experiments and mouse wound disinfection demonstrate the ultrarobust and recyclable disinfection capability of nanoagents with nearly 100% killing ratio to Staphylococcus aureus. Overall, for the first time, we represent a pioneering study on designing nonchemotherapic and robust dual‐responsive nanoagents that can sensitively and reversibly trap, inactivate, and detach bacteria. We envision that such nanoagents will not only have potential applications in pathogenic bacteria prevention but also provide a new pathway for wound disinfection, implant sterilization, and also live bacteria transportation.     

Enhanced Osteoblast Adhesion to Epoxide‐Functionalized Surfaces

As an alternative to expensive extracellular matrix (ECM) proteins generally applied as coatings in Petri dishes used for cell binding, an innovative system based on epoxide‐functionalized monolayers capable of protein binding is proposed. Since cells bind to material surfaces through proteins, protein‐binding surfaces should also promote cell binding. Here we investigate how the cell‐binding properties of an epoxide‐functionalized surface compares with ECM protein gel coated surfaces and tissue culture polystyrene control surfaces. Glass surfaces are functionalized with glycidoxypropyltriethoxysilane (GOPS), which results in an epoxide‐functionalized surface capable of binding proteins through an epoxide–amine reaction. Advancing contact angle measurements and atomic force microscopy measurements confirm the formation of a homogeneous GOPS monolayer. This monolayer is micropatterned with fluorescein‐labeled ECM protein gel by microcontact printing (µCP). Confocal laser scanning microscopy (CLSM) shows accurately transferred ECM protein gel micropatterns. Osteoblasts that are seeded on these micropatterned substrates show a clear preference for adhering to the epoxide‐functionalized areas. The morphology of these cultured osteoblasts is needle‐like with high aspect ratios. As controls, osteoblasts are cultured on GOPS‐functionalized surfaces, unstructured ECM protein gel surfaces, and tissue culture polystyrene (TCPS). The GOPS surfaces demonstrate a drastic increase in cell adhesion after 2 h, whilst the other tests show no adverse effects of this surface on the osteoblasts as compared to ECM and TCPS. CLSM shows healthy cell morphologies on each surface. It is demonstrated for the first time that epoxide groups outperform ECM protein gel in cell adhesion, thereby providing new routes for cost‐effective coatings that improve biocompatibility as well as exciting, new methodologies to control and direct cell adhesion.     

Interaction of Zoospores of the Green Alga Ulva with Bioinspired Micro‐ and Nanostructured Surfaces Prepared by Polyelectrolyte Layer‐by‐Layer Self‐Assembly

The interaction of spores of Ulva with bioinspired structured surfaces in the nanometer–micrometer size range is investigated using a series of coatings with systematically varying morphology and chemistry, which allows separation of the contributions of morphology and surface chemistry to settlement (attachment) and adhesion strength. Structured surfaces are prepared by layer‐by‐layer spray‐coating deposition of polyelectrolytes. By changing the pH during application of oppositely charged poly(acrylic acid) and polyethylenimine polyelectrolytes, the surface structures are systematically varied, which allows the influence of morphology on the biological response to be determined. In order to discriminate morphological from chemical effects, surfaces are chemically modified with poly(ethylene glycol) and tridecafluoroctyltriethoxysilane. This chemical modification changes the water contact angles while the influence of the morphology is retained. The lowest level of settlement is observed for structures of the order 2 µm. All surfaces are characterized with respect to their wettability, chemical composition, and morphological properties by contact angle measurement, X‐ray photoelectron spectroscopy, scanning electron microscopy, and atomic force microscopy.     

Novel Triclosan‐Bound Hybrid‐Silica Nanoparticles and their Enhanced Antimicrobial Properties

The design and synthesis of novel hybrid‐silica nanoparticles (NPs) containing the FDA‐approved antimicrobial triclosan (Irgasan) covalently linked within the inorganic matrix for its controlled, slow release upon interaction, is reported. The NPs are in the range of 130 ± 30 nm in diameter, with a smooth and spherical morphology. Characterization of the hybrid‐silica NPs containing triclosan, namely T‐SNPs, and their appropriate linkers is accomplished by microscopic and spectroscopic techniques. Preliminary antimicrobial activity is studied through bacterial‐growth experiments. The T‐SNPs are found to be superior in killing bacteria, as compared with the free biocide.     

Controlled Release of LL‐37‐Derived Synthetic Antimicrobial and Anti‐Biofilm Peptides SAAP‐145 and SAAP‐276 Prevents Experimental Biomaterial‐Associated Staphylococcus aureus Infection

The present study aims to develop an implant coating releasing novel antimicrobial agents to prevent biomaterial‐associated infections. The LL‐37‐derived synthetic antimicrobial and anti‐biofilm peptides (SAAP)‐145 and SAAP‐276 exhibit potent bactericidal and anti‐biofilm activities against clinical and multidrug‐resistant Staphylococcus aureus strains by rapid membrane permeabilization, without inducing resistance. Injection of SAAP‐145, but not SAAP‐276, along subcutaneous implants in mice reduces S. aureus implant colonization by approximately 2 log, but does not reduce bacterial numbers in surrounding tissue. To improve their efficacy, SAAP‐145 and SAAP‐276 are incorporated in a polymer–lipid encapsulation matrix (PLEX) coating, providing a constant release of 0.6% daily up to 30 d after an initial burst release of >50%. In a murine model for biomaterial‐associated infection, SAAP‐145‐PLEX and SAAP‐276‐PLEX coatings significantly reduce the number of culture positive implants and show ≥3.5 and ≥1.5 log lower S. aureus implant and tissue colonization, respectively. Interestingly, these peptide coatings are also highly effective against multidrug‐resistant S. aureus, both reducing implant colonization by ≥2 log. SAAP‐276‐PLEX additionally reduces tissue colonization by 1 log. Together, the peptide‐releasing PLEX coatings hold promise for further development as an alternative to coatings releasing conventional antibiotics to prevent biomaterial‐associated infections.