RESUMEN
Blood-contacting medical devices play an important role within healthcare and are required to be biocompatible, hemocompatible and resistant to microbial colonization. Here we describe a high throughput screen for copolymers with these specific properties. A series of weakly amphiphilic monomers are combinatorially polymerized with acrylate glycol monomers of varying chain lengths to create a library of 645 multi-functional candidate materials containing multiple chemical moieties that impart anti-biofilm, hemo- and immuno-compatible properties. These materials are screened in over 15,000 individual biological assays, targeting two bacterial species, one Gram negative (Pseudomonas aeruginosa) and one Gram positive (Staphylococcus aureus) commonly associated with central venous catheter infections, using 5 different measures of hemocompatibility and 6 measures of immunocompatibililty. Selected copolymers reduce platelet activation, platelet loss and leukocyte activation compared with the standard comparator PTFE as well as reducing bacterial biofilm formation in vitro by more than 82% compared with silicone. Poly(isobornyl acrylate-co-triethylene glycol methacrylate) (75:25) is identified as the optimal material across all these measures reducing P. aeruginosa biofilm formation by up to 86% in vivo in a murine foreign body infection model compared with uncoated silicone.
Asunto(s)
Antibacterianos , Infecciones Estafilocócicas , Animales , Biopelículas , Ratones , Pseudomonas aeruginosa , Staphylococcus aureusRESUMEN
Developing medical devices that resist bacterial attachment and subsequent biofilm formation is highly desirable. In this paper, we report the optimization of the molecular structure and thus material properties of a range of (meth)acrylate copolymers which contain monomers reported to deliver bacterial resistance to surfaces. This optimization allows such monomers to be employed within novel coatings to reduce bacterial attachment to silicone urinary catheters. We show that the flexibility of copolymers can be tuned to match that of the silicone catheter substrate, by copolymerizing these polymers with a lower Tg monomer such that it passes the flexing fatigue tests as coatings upon catheters, that the homopolymers failed. Furthermore, the Tg values of the copolymers are shown to be readily estimated by the Fox equation. The bacterial resistance performance of these copolymers were typically found to be better than the neat silicone or a commercial silver containing hydrogel surface, when the monomer feed contained only 25 v% of the "hit" monomer. The method of initiation (either photo or thermal) was shown not to affect the bacterial resistance of the copolymers. Optimized synthesis conditions to ensure that the correct copolymer composition and to prevent the onset of gelation are detailed.
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Acrilatos/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Adhesión Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana , Polímeros/farmacología , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Sustancias Macromoleculares/química , Polimerizacion , Polímeros/químicaRESUMEN
Improved biomaterials are required for application in regenerative medicine, biosensing, and as medical devices. The response of cells to the chemistry of polymers cultured in media is generally regarded as being dominated by proteins adsorbed to the surface. Here we use mass spectrometry to identify proteins adsorbed from a complex mouse embryonic fibroblast (MEF) conditioned medium found to support pluripotent human embryonic stem cell (hESC) expansion on a plasma etched tissue culture polystyrene surface. A total of 71 proteins were identified, of which 14 uniquely correlated with the surface on which pluripotent stem cell expansion was achieved. We have developed a microarray combinatorial protein spotting approach to test the potential of these 14 proteins to support expansion of a hESC cell line (HUES-7) and a human induced pluripotent stem cell line (ReBl-PAT) on a novel polymer (N-(4-Hydroxyphenyl) methacrylamide). These proteins were spotted to form a primary array yielding several protein mixture 'hits' that enhanced cell attachment to the polymer. A second array was generated to test the function of a refined set of protein mixtures. We found that a combination of heat shock protein 90 and heat shock protein-1 encourage elevated adherence of pluripotent stem cells at a level comparable to fibronectin pre-treatment.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Células Madre Embrionarias Humanas/citología , Proteínas de la Membrana/metabolismo , Animales , Línea Celular , Proliferación Celular , Humanos , Células Madre Pluripotentes/citología , Polímeros/metabolismoRESUMEN
A scalable and cost-effective synthetic polymer substrate that supports robust expansion and subsequent multilineage differentiation of human pluripotent stem cells (hPSCs) with defined commercial media is presented. This substrate can be applied to common cultureware and used off-the-shelf after long-term storage. Expansion and differentiation of hPSCs are performed entirely on the polymeric surface, enabling the clinical potential of hPSC-derived cells to be realized.
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Técnicas de Cultivo de Célula/instrumentación , Diferenciación Celular/fisiología , Células Madre Pluripotentes/fisiología , Polímeros , Adhesión Celular/fisiología , Línea Celular , Linaje de la Célula , Medios de Cultivo , Técnica del Anticuerpo Fluorescente , Ensayos Analíticos de Alto Rendimiento , Humanos , Análisis por MicromatricesRESUMEN
Cardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components such as the substrate on which cells adhere to are important variables controlling the biological activity of cells. Using a combinatorial materials approach we develop a synthetic, chemically defined cellular niche for the support of functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) in a serum-free fully defined culture system. Almost 700 polymers were synthesized and evaluated for their utility as growth substrates. From this group, 20 polymers were identified that supported cardiomyocyte adhesion and spreading. The most promising 3 polymers were scaled up for extended culture of hESC-CMs for 15 days and were characterized using patch clamp electrophysiology and myofibril analysis to find that functional and structural phenotype was maintained on these synthetic substrates without the need for coating with extracellular matrix protein. In addition, we found that hESC-CMs cultured on a co-polymer of isobornyl methacrylate and tert-butylamino-ethyl methacrylate exhibited significantly longer sarcomeres relative to gelatin control. The potential utility of increased structural integrity was demonstrated in an in vitro toxicity assay that found an increase in detection sensitivity of myofibril disruption by the anti-cancer drug doxorubicin at a concentration of 0.05 µM in cardiomyocytes cultured on the co-polymer compared to 0.5 µM on gelatin. The chemical moieties identified in this large-scale screen provide chemically defined conditions for the culture and manipulation of hESC-CMs, as well as a framework for the rational design of superior biomaterials.
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Técnicas de Cultivo Celular por Lotes/métodos , Materiales Biocompatibles/síntesis química , Miocitos Cardíacos/citología , Miocitos Cardíacos/fisiología , Células Madre/citología , Células Madre/fisiología , Adhesión Celular/fisiología , Diferenciación Celular/fisiología , Línea Celular , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Técnicas Químicas Combinatorias , Medio de Cultivo Libre de Suero , Humanos , Ensayo de Materiales/métodos , Polímeros/síntesis químicaRESUMEN
For ternary solid dispersions, it is indispensable to characterize their structure, phase behavior, and the spatial distribution of the dispersed drug as this might influence the release profile and/or stability of these formulations. This study shows how formulation (feed concentration) and process (feed rate, inlet air temperature, and atomizing air pressure) parameters can influence the characteristics of ternary spray-dried solid dispersions. The microspheres considered here consist of a poly(lactic-co-glycolic acid) (PLGA) surface layer and an underlying polyvinylpyrrolidone (PVP) phase. A poorly soluble active pharmaceutical ingredient (API) was molecularly dispersed in this matrix. Differences were observed in component miscibility, phase heterogeneity, particle size, morphology, as well as API surface coverage for selected spray-drying parameters. Observed differences are likely because of changes in the droplet generation, evaporation, and thus particle formation processes. However, varying particle characteristics did not influence the drug release of the formulations studied, indicating the robustness of this approach to produce particles of consistent drug release characteristics. This is likely because of the fact that the release is dominated by diffusion from the PVP layer through pores in the PLGA surface layer and that observed differences in the latter have no influence on the release.
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Desecación , Ácido Láctico/química , Preparaciones Farmacéuticas/química , Ácido Poliglicólico/química , Povidona/química , Tecnología Farmacéutica/métodos , Aerosoles , Presión del Aire , Química Farmacéutica , Preparaciones de Acción Retardada , Difusión , Inyecciones , Cinética , Microesferas , Modelos Químicos , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Solubilidad , Propiedades de Superficie , TemperaturaRESUMEN
A new class of material resistant to bacterial attachment has been discovered that is formed from polyacrylates with hydrocarbon pendant groups. In this study, the relationship between the nature of the hydrocarbon moiety and resistance to bacteria is explored, comparing cyclic, aromatic, and linear chemical groups. A correlation is shown between bacterial attachment and a parameter derived from the partition coefficient and the number of rotatable bonds of the materials' pendant groups. This correlation is applicable to 86% of the hydrocarbon pendant moieties surveyed, quantitatively supporting the previous qualitative observation that bacteria are repelled from poly(meth)acrylates containing a hydrophilic ester group when the pendant group is both rigid and hydrophobic. This insight will help inform and predict the further development of polymers resistant to bacterial attachment.
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Adhesión Bacteriana/fisiología , Ácidos Polimetacrílicos/metabolismo , Pseudomonas aeruginosa/química , Pseudomonas aeruginosa/fisiología , Biopelículas , Interacciones Hidrofóbicas e Hidrofílicas , Docilidad , Ácidos Polimetacrílicos/química , Pseudomonas aeruginosa/metabolismo , Propiedades de SuperficieRESUMEN
At present no scientific rationale exists for selecting a particular enabling strategy to formulate a poorly water-soluble drug, although this is crucial as it will influence the in vivo performance of the resulting formulation. This study provides an insight into this complicated decision making process for a poorly soluble human immunodeficiency virus (HIV) protease inhibitor based upon in vivo test results. A formulation strategy based on the molecular dispersion of this active pharmaceutical ingredient (API) into a biphasic matrix consisting of water-insoluble poly(lactic-co-glycolic acid) (PLGA) and water-soluble polyvinylpyrrolidone (PVP) was evaluated. The long-term in vivo performance of this strategy was compared to that of other solubility enhancing approaches by evaluating exposure of the API in male Beagle dogs. Solid dispersions, based on a PLGA/PVP matrix, were compared to solid dispersions in a pure PLGA matrix. Additionally these solid dispersion strategies were compared to the strategy of particle size reduction by means of an API microsuspension. The in vivo performance of the various formulations over a period of 28days after intramuscular injection was evaluated by the observed initial burst release, plasma concentration-time profiles, time at which maximum plasma levels were reached and the estimated bioavailability. Compared to the other formulation strategies assessed, it was concluded that the addition of PVP in a PLGA matrix resulted in vivo in a more sustained release as well as a higher amount of drug released from the polymeric matrix. This was explained based on the structure of these binary PLGA/PVP matrices where the pore network originating from rapidly dissolving PVP plays a key role. Moreover, the results suggest that the API release from this type of formulation could be delayed by increasing the amount of PLGA in the formulation.
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Inhibidores de la Proteasa del VIH/administración & dosificación , Animales , Disponibilidad Biológica , Química Farmacéutica , Preparaciones de Acción Retardada , Perros , Composición de Medicamentos , Excipientes , Inhibidores de la Proteasa del VIH/farmacocinética , Semivida , Humanos , Inyecciones Intramusculares , Inyecciones Intravenosas , Ácido Láctico , Masculino , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Povidona , SuspensionesRESUMEN
Understanding and controlling the in vitro release behavior of a formulation is a first step toward rationalized selection of a solubility enhancing formulation strategy with a desired release profile in vivo. Therefore six model formulations, representing three different formulation strategies, were physicochemically analyzed and their in vitro release was determined. Solid dispersions based on a PLGA/PVP matrix were compared to solid dispersions in a pure PLGA matrix. Additionally these solid dispersion strategies were compared to the strategy of particle size reduction by means of an API microsuspension. Depending on composition and manufacturing method, formulations varied in particle size, porosity, phase behavior, surface coverage and physical state of the API. This resulted in observed differences in their in vitro release profile. For the various formulation strategies tested both a porous PLGA-based formulation and PLGA/PVP-based formulations, resulted in vitro in sustained release of the poorly soluble API with over 50% of drug released after 24h. For PLGA-based formulations the porosity was identified as a critical parameter influencing in vitro drug release. For the PLGA/PVP-based formulations the release rate can be tailored by the amount of PLGA present. Particle size reduction resulted in immediate total drug release.
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Preparaciones de Acción Retardada/química , Ácido Láctico/química , Preparaciones Farmacéuticas/química , Ácido Poliglicólico/química , Química Farmacéutica/métodos , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Inyecciones , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/química , Polivinilos/química , Porosidad , Pirrolidinas/química , SolubilidadRESUMEN
PURPOSE: Miscibility of the different compounds that make up a solid dispersion based formulation play a crucial role in the drug release profile and physical stability of the solid dispersion as it defines the phase behaviour of the dispersion. The standard technique to obtain information on phase behaviour of a sample is (modulated) differential scanning calorimetry ((M)DSC). However, for ternary mixtures (M)DSC alone is not sufficient to characterize their phase behaviour and to gain insight into the distribution of the active pharmaceutical ingredient (API) in a two-phased polymeric matrix. METHODS: MDSC was combined with complementary surface analysis techniques, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Three spray-dried model formulations with varying API/PLGA/PVP ratios were analyzed. RESULTS: MDSC, TOF-SIMS and AFM provided insights into differences in drug distribution via the observed surface coverage for 3 differently composed ternary solid dispersions. CONCLUSIONS: Combining MDSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions.
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Química Farmacéutica/métodos , Portadores de Fármacos/química , Inhibidores de la Proteasa del VIH/química , Ácido Láctico/química , Ácido Poliglicólico/química , Rastreo Diferencial de Calorimetría , Microscopía de Fuerza Atómica , Microscopía Electrónica de Rastreo , Microesferas , Estructura Molecular , Transición de Fase , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Solubilidad , Espectrometría de Masa de Ion Secundario , Propiedades de Superficie , Temperatura de TransiciónRESUMEN
Using microarray technologies thousands of biomedical materials can be screened in a rapid, parallel and cost effective fashion to identify the optimum candidate that fulfils a specific biomedical application. High throughput surface characterization (HTSC) of printed microarrays has played a key role in the discovery and development of biomedical materials. This review focuses on the production and HTSC of microarrays, their application in specific biomedical fields and a future perspective on the development of this technology.
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Materiales Biocompatibles , Descubrimiento de Drogas/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Análisis por Micromatrices , Investigación Biomédica , Portadores de Fármacos , Humanos , Polímeros , Células MadreRESUMEN
Polymeric substrates are being identified that could permit translation of human pluripotent stem cells from laboratory-based research to industrial-scale biomedicine. Well-defined materials are required to allow cell banking and to provide the raw material for reproducible differentiation into lineages for large-scale drug-screening programs and clinical use. Yet more than 1 billion cells for each patient are needed to replace losses during heart attack, multiple sclerosis and diabetes. Producing this number of cells is challenging, and a rethink of the current predominant cell-derived substrates is needed to provide technology that can be scaled to meet the needs of millions of patients a year. In this Review, we consider the role of materials discovery, an emerging area of materials chemistry that is in large part driven by the challenges posed by biologists to materials scientists.
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Materiales Biocompatibles/química , Técnicas de Cultivo de Célula/métodos , Células Madre/citología , Animales , Técnicas de Cultivo de Célula/instrumentación , Diabetes Mellitus/metabolismo , Diabetes Mellitus/terapia , Evaluación Preclínica de Medicamentos/métodos , Humanos , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/terapia , Infarto del Miocardio/metabolismo , Infarto del Miocardio/terapia , Trasplante de Células Madre , Células Madre/metabolismoRESUMEN
The thermally triggered release of up to 96% of attached uropathogenic E. coli is achieved on two polymers with opposite changes in surface wettability upon reduction in temperature. This demonstrates that the bacterial attachment to a surface cannot be explained in terms of water contact angle alone; rather, the surface composition of the polymer plays the key role.
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Adhesión Bacteriana/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Polímeros/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Escherichia coli/química , Escherichia coli/fisiología , Polímeros/química , Propiedades de Superficie , Temperatura , HumectabilidadRESUMEN
New classes of information-rich DNA block co-polymer conjugates were synthesised, encoded with thermoresponsive and biocompatible poly(tri(ethylene glycol)ethyl ether methacrylate) (pTriEGMA) chains and oligomeric nucleic acids connected by either bioreducible or non-reducible links. The pTriEGMA chains were grown from initiator-functionalised hybridised DNA, designed to assemble with toehold overhangs. Functional information in the conjugates was explored via dynamic light scattering (DLS) and atomic force microscopy (AFM), in order to evaluate (i) reversible self-assembly into supramolecular structures across the pTriEGMA phase transition temperature; (ii) conformational change via addition of competing DNA sequences across the toeholds, and (iii) reductive cleavage of polymer-DNA links. The results showed that discrete nanoscale conjugates could reversibly associate through pTriEGMA phase behaviour and that size and association behaviour in one class of conjugate could be switched by addition of a competing DNA sequence and by reduction to break the polymer-DNA links. Preliminary experiments with the DNA-conjugates as delivery systems for doxorubicin to a cancer cell line indicated good tolerability of the conjugates alone and cytotoxic efficacy when loaded with the drug.
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ADN/química , Polímeros/química , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/toxicidad , Materiales Biocompatibles/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/toxicidad , Portadores de Fármacos/química , Humanos , Luz , Microscopía de Fuerza Atómica , Hibridación de Ácido Nucleico , Transición de Fase , Dispersión de Radiación , Temperatura de TransiciónRESUMEN
In view of the increasing interest in injectable controlled release formulations for the treatment of chronic diseases, injectable polymeric microspheres consisting of a surface layer of poly(lactic-co-glycolic acid) (PLGA) and an underlying polyvinylpyrrolidone (PVP) layer were previously developed. The present study focuses on the influence of heat and humidity on the surface characteristics of these spray-dried PLGA/PVP microspheres. The response of the polymeric matrix to these factors will provide an insight into the expected release behavior and stability of the formulation. This should result in the development of a drug matrix with desired and tunable characteristics in terms of physicochemical stability and drug release profile, relevant in a later stage of research. Glass transition temperatures (Tgs) and miscibility behavior were analyzed by modulated differential scanning calorimetry (MDSC). Scanning electron microscopy (SEM) provided insight in particle morphology. Atomic force microscopy (AFM) was used to study the nanoscale topography and phase behavior of the samples. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) were utilized for surface chemical analysis and quantification respectively. It could be concluded that the surface characteristics (chemical composition, phase behavior, and topography) of spray-dried PVP/PLGA microparticles were affected by exposure to heat and humidity. When exposed to these conditions, a surface rearrangement occurs whereby an increase of PVP at the surface is observed, coupled with a decrease in PLGA. This phenomenon can be explained based upon the relative thermal characteristics and consequent molecular mobility of the two polymers.
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Ácido Láctico/química , Microesferas , Ácido Poliglicólico/química , Polímeros/química , Povidona/química , Calor , Humedad , Microscopía de Fuerza Atómica , Copolímero de Ácido Poliláctico-Ácido PoliglicólicoRESUMEN
Small interfering ribonucleic acids (siRNAs) form potentially the most important class of next generation therapeutics. However, achieving their efficient delivery in the correct dose, time and location in the body remains a significant challenge. Rapid developments in the chemistries of siRNA formulations are enabling new strategies to overcome the core obstacles to delivery which include poor ribonuclease (RNase) resistance, short biological half-life, lack of tissue targeting, inefficient cellular uptake and undesirable toxicity. In this review we describe these principal challenges and evaluate recent approaches proposed to overcome the chemical, biochemical and physiological barriers. The role of the specific chemical structure of siRNA is considered and an overview of selected literature-reported siRNA formulations is provided. These include chemically-modified siRNAs and analogues, aptamer-siRNA chimeras, self-assembled nanoparticles, lipid and polymer complexes, bioconjugates and fusion protein complexes. We conclude the review with an outlook for the clinical use of this highly promising, but pharmaceutically challenging biotherapeutic.
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Sistemas de Liberación de Medicamentos/métodos , Nanomedicina/métodos , ARN Interferente Pequeño/química , Animales , Investigación Biomédica , Humanos , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genéticaRESUMEN
Polymer microarrays are a key enabling technology for high throughput materials discovery. In this study, multivariate image analysis, specifically multivariate curve resolution (MCR), is applied to the hyperspectral time of flight secondary ion mass spectroscopy (ToF-SIMS) data from eight individual microarray spots. Rather than analysing the data individually, the data-sets are collated and analysed as a single large data-set. Desktop computing is not a practical method for undertaking MCR analysis of such large data-sets due to the constraints of memory and computational overhead. Here, a distributed memory High-Performance Computing facility (HPC) is used. Similar to what is achieved using MCR analysis of individual samples, the results from this consolidated data-set allow clear identification of the substrate material; furthermore, specific chemistries common to different spots are also identified. The application of the HPC facility to the MCR analysis of ToF-SIMS hyperspectral data-sets demonstrates a potential methodology for the analysis of macro-scale data without compromising spatial resolution (data 'binning'). Copyright © 2012 John Wiley & Sons, Ltd.
RESUMEN
A new class of bacteria-attachment-resistant materials is discovered using a multi-generation polymer microarray methodology that reduces bacterial attachment by up to 99.3% compared with a leading commercially available silver hydrogel anti-bacterial material. The coverage of three bacterial species, Pseudomonas aeruginosa, Staphylococcus aureus, and uropathogenic Escherichia coli is assessed.
Asunto(s)
Adhesión Bacteriana/efectos de los fármacos , Diseño de Fármacos , Análisis por Micromatrices , Ácidos Polimetacrílicos/farmacología , Ácidos Polimetacrílicos/química , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/fisiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiologíaRESUMEN
Polymer microarrays are a key enabling technology for the discovery of novel materials. This technology can be further enhanced by expanding the combinatorial space represented on an array. However, not all materials are compatible with the microarray format and materials must be screened to assess their suitability with the microarray manufacturing methodology prior to their inclusion in a materials discovery investigation. In this study a library of materials expressed on the microarray format are assessed by light microscopy, atomic force microscopy and time-of-flight secondary ion mass spectrometry to identify compositions with defects that cause a polymer spot to exhibit surface properties significantly different from a smooth, round, chemically homogeneous 'normal' spot. It was demonstrated that the presence of these defects could be predicted in 85% of cases using a partial least square regression model based upon molecular descriptors of the monomer components of the polymeric materials. This may allow for potentially defective materials to be identified prior to their formation. Analysis of the PLS regression model highlighted some chemical properties that influenced the formation of defects, and in particular suggested that mixing a methacrylate and an acrylate monomer and/or mixing monomers with long and linear or short and bulky pendant groups will prevent the formation of defects. These results are of interest for the formation of polymer microarrays and may also inform the formulation of printed polymer materials generally.
RESUMEN
Bacterial attachment and subsequent biofilm formation pose key challenges to the optimal performance of medical devices. In this study, we determined the attachment of selected bacterial species to hundreds of polymeric materials in a high-throughput microarray format. Using this method, we identified a group of structurally related materials comprising ester and cyclic hydrocarbon moieties that substantially reduced the attachment of pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli). Coating silicone with these 'hit' materials achieved up to a 30-fold (96.7%) reduction in the surface area covered by bacteria compared with a commercial silver hydrogel coating in vitro, and the same material coatings were effective at reducing bacterial attachment in vivo in a mouse implant infection model. These polymers represent a class of materials that reduce the attachment of bacteria that could not have been predicted to have this property from the current understanding of bacteria-surface interactions.