ORCID Profile
0000-0001-5182-493X
Current Organisation
University of Nottingham
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Publisher: Royal Society of Chemistry (RSC)
Date: 2003
DOI: 10.1039/B305445B
Publisher: Wiley
Date: 28-12-2020
Publisher: Elsevier BV
Date: 04-2012
Publisher: Elsevier BV
Date: 12-2010
Publisher: American Chemical Society (ACS)
Date: 02-01-2018
Abstract: Bacterial infections in healthcare settings are a frequent accompaniment to both routine procedures such as catheterization and surgical site interventions. Their impact is becoming even more marked as the numbers of medical devices that are used to manage chronic health conditions and improve quality of life increases. The resistance of pathogens to multiple antibiotics is also increasing, adding an additional layer of complexity to the problems of employing safe and effective medical procedures. One approach to reducing the rate of infections associated with implanted and indwelling medical devices is the use of polymers that resist the formation of bacterial biofilms. To significantly accelerate the discovery of such materials, we show how state of the art machine learning methods can generate quantitative predictions for the attachment of multiple pathogens to a large library of polymers in a single model for the first time. Such models facilitate design of polymers with very low pathogen attachment across different bacterial species that will be candidate materials for implantable or indwelling medical devices such as urinary catheters, cochlear implants, and pacemakers.
Publisher: MyJove Corporation
Date: 25-01-2012
DOI: 10.3791/3636
Publisher: Springer Science and Business Media LLC
Date: 22-08-2010
DOI: 10.1038/NMAT2812
Publisher: American Chemical Society (ACS)
Date: 02-11-2016
Publisher: Elsevier BV
Date: 04-2016
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9BM00875F
Abstract: Optical fibre sensors successfully detect and quantify bacterial attachment and biofilm formation on uncoated and coated endotracheal tube surfaces.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 27-01-2023
Abstract: Innovative approaches to prevent catheter-associated urinary tract infections (CAUTIs) are urgently required. Here, we describe the discovery of an acrylate copolymer capable of resisting single- and multispecies bacterial biofilm formation, swarming, encrustation, and host protein deposition, which are major challenges associated with preventing CAUTIs. After screening ~400 acrylate polymers, poly( tert -butyl cyclohexyl acrylate) was selected for its biofilm- and encrustation-resistant properties. When combined with the swarming inhibitory poly(2-hydroxy-3-phenoxypropyl acrylate), the copolymer retained the bioinstructive properties of the respective homopolymers when challenged with Proteus mirabilis , Pseudomonas aeruginosa , Staphylococcus aureus , and Escherichia coli . Urinary tract catheterization causes the release of host proteins that are exploited by pathogens to colonize catheters. After preconditioning the copolymer with urine collected from patients before and after catheterization, reduced host fibrinogen deposition was observed, and resistance to erse uropathogens was maintained. These data highlight the potential of the copolymer as a urinary catheter coating for preventing CAUTIs.
Publisher: Cold Spring Harbor Laboratory
Date: 10-10-2020
DOI: 10.1101/2020.10.10.328146
Abstract: Bio-instructive materials that prevent bacterial biofilm formation and drive an appropriate host immune response have the potential to significantly reduce the burden of medical device-associated infections. Since bacterial surface attachment is known to be sensitive to surface topography, we experimentally survey 2,176 combinatorially generated shapes using an unbiased high-throughput micro topographical screen on polystyrene. This identifies topographies that reduce colonization in vitro by up to 15-fold compared with a flat surface for both motile and non-motile bacterial pathogens. Equivalent reductions are achieved on polyurethane, a polymer commonly used in medical devices. Using machine learning methods, a set of design rules based on generalisable descriptors is established for predicting bacteria-resistant micro topographies. In a murine foreign body infection model, anti-attachment topographies are shown to be refractory to P. aeruginosa and to recruit a productive host response, highlighting the potential of simple topographical patterning of non-eluting implants for preventing medical device associated infections.
Publisher: American Chemical Society (ACS)
Date: 07-03-2023
Publisher: Wiley
Date: 03-10-2019
Publisher: Informa UK Limited
Date: 14-10-2010
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1SM06063E
Publisher: Wiley
Date: 06-2015
Publisher: American Chemical Society (ACS)
Date: 20-06-2019
Abstract: Surface-functionalized microparticles are relevant to fields spanning engineering and biomedicine, with uses ranging from cell culture to advanced cell delivery. Varying topographies of biomaterial surfaces are also being investigated as mediators of cell-material interactions and subsequent cell fate. To investigate competing or synergistic effects of chemistry and topography in three-dimensional cell cultures, methods are required to introduce these onto microparticles without modification of their underlying morphology or bulk properties. In this study, a new approach for surface functionalization of poly(lactic acid) (PLA) microparticles is reported that allows decoration of the outer shell of the polyesters with additional polymers via aqueous atom transfer radical polymerization routes. PLA microparticles with smooth or dimpled surfaces were functionalized with poly(poly(ethylene glycol) methacrylate) and poly[
Publisher: American Association for the Advancement of Science (AAAS)
Date: 05-06-2020
Abstract: Anti-attachment materials that are sprayable and 3D-printable passively prevent colonization by harmful fungi.
Publisher: Wiley
Date: 27-05-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2TB00379A
Publisher: Wiley
Date: 09-12-2014
Publisher: Springer Science and Business Media LLC
Date: 21-05-2014
DOI: 10.1038/NMAT3972
Abstract: 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.
Publisher: American Chemical Society (ACS)
Date: 23-10-2018
Abstract: The identification of biomaterials that modulate cell responses is a crucial task for tissue engineering and cell therapy. The identification of novel materials is complicated by the immense number of synthesizable polymers and the time required for testing each material experimentally. In the current study, polymeric biomaterial-cell interactions were assessed rapidly using a microarray format. The attachment, proliferation, and differentiation of human dental pulp stem cells (hDPSCs) were investigated on 141 homopolymers and 400 erse copolymers. The copolymer of isooctyl acrylate and 2-(methacryloyloxy)ethyl acetoacetate achieved the highest attachment and proliferation of hDPSC, whereas high cell attachment and differentiation of hDPSC were observed on the copolymer of isooctyl acrylate and trimethylolpropane ethoxylate triacrylate. Computational models were generated, relating polymer properties to cellular responses. These models could accurately predict cell behavior for up to 95% of materials within a test set. The models identified several functional groups as being important for supporting specific cell responses. In particular, oxygen-containing chemical moieties, including fragments from the acrylate/acrylamide backbone of the polymers, promoted cell attachment. Small hydrocarbon fragments originating from polymer pendant groups promoted cell proliferation and differentiation. These computational models constitute a key tool to direct the discovery of novel materials within the enormous chemical space available to researchers.
Publisher: American Chemical Society (ACS)
Date: 26-08-2016
Publisher: American Chemical Society (ACS)
Date: 06-11-2020
Publisher: Wiley
Date: 18-02-2013
Publisher: Wiley
Date: 04-02-2014
Publisher: Springer Science and Business Media LLC
Date: 16-11-2011
DOI: 10.1007/S10856-011-4474-5
Abstract: Three different formulations comprising two drugs, felodipine and hydrochlorothiazide (HCT) and two polymers, poly(vinyl pyrolidone) (PVP) and poly(lactic-co-glycolic acid) (PLGA) were inkjet printed as micro-dot arrays and analysed on an in idual micro-spot basis by time-of-flight secondary ion mass spectrometry (ToF-SIMS). For the HCT/PLGA formulation, the spots showed heterogeneity of the drug and other chemical constituents. To further investigate these heterogeneities, multivariate curve resolution was applied to the ToF-SIMS hyperspectral image datasets. This approach successfully identified distinct chemical components elucidating the HCT, PLGA, substrate material, and contaminants based on sulphur, phosphorous and sodium chloride. Spots printed using either of the drugs with PVP exhibited full substrate coverage and a uniform distribution of the active ingredient along with all other constituents within the printed spot area. This represents the preferred situation in terms of stability and controlling the release of a drug from a polymer matrix.
Publisher: American Vacuum Society
Date: 23-05-2017
DOI: 10.1116/1.4984011
Abstract: Catheter associated urinary tract infections are the most common health related infections worldwide, contributing significantly to patient morbidity and mortality and increased health care costs. To reduce the incidence of these infections, new materials that resist bacterial biofilm formation are needed. A composite catheter material, consisting of bulk poly(dimethylsiloxane) (PDMS) coated with a novel bacterial biofilm resistant polyacrylate [ethylene glycol dicyclopentenyl ether acrylate (EGDPEA)-co-di(ethyleneglycol) methyl ether methacrylate (DEGMA)], has been proposed. The coated material shows excellent bacterial resistance when compared to commercial catheter materials, but delamination of the EGDPEA-co-DEGMA coatings under mechanical stress presents a challenge. In this work, the use of oxygen plasma treatment to improve the wettability and reactivity of the PDMS catheter material and improve adhesion with the EGDPEA-co-DEGMA coating has been investigated. Argon cluster three dimensional-imaging time-of-flight secondary ion mass spectrometry (ToF-SIMS) has been used to probe the buried adhesive interface between the EGDPEA-co-DEGMA coating and the treated PDMS. ToF-SIMS analysis was performed in both dry and frozen-hydrated states, and the results were compared to mechanical tests. From the ToF-SIMS data, the authors have been able to observe the presence of PDMS, silicates, salt particles, cracks, and water at the adhesive interface. In the dry catheters, low molecular weight PDMS oligomers at the interface were associated with poor adhesion. When hydrated, the hydrophilic silicates attracted water to the interface and led to easy delamination of the coating. The best adhesion results, under hydrated conditions, were obtained using a combination of 5 min O2 plasma treatment and silane primers. Cryo-ToF-SIMS analysis of the hydrated catheter material showed that the bond between the primed PDMS catheter and the EGDPEA-co-DEGMA coating was stable in the presence of water. The resulting catheter material resisted Escherichia coli and Proteus mirabilis biofilm colonization by up to 95% compared with uncoated PDMS after 10 days of continuous bacterial exposure and had the mechanical properties necessary for use as a urinary catheter.
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.BIOMATERIALS.2009.09.037
Abstract: The high throughput discovery of new bio materials can be achieved by rapidly screening many different materials synthesised by a combinatorial approach to identify the optimal composition that fulfils a particular biomedical application. Here we review the literature in this area and conclude that for polymers this process is best achieved in a microarray format, which enable thousands of cell-material interactions to be monitored on a single chip. Polymer microarrays can be formed by printing pre-synthesised polymers or by printing monomers onto the chip where on-slide polymerisation is initiated. The surface properties of the material can be analysed and correlated to the biological performance using high throughput surface analysis, including time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS) and water contact angle (WCA) measurements. This approach enables the surface properties responsible for the success of a material to be understood, which in turn provides the foundations of future material design. The high throughput discovery of materials using polymer microarrays has been explored for many cell-based applications including the isolation of specific cells from heterogeneous populations, the attachment and differentiation of stem cells and the controlled transfection of cells. Further development of polymerisation techniques and high throughput biological assays amenable to the polymer microarray format will broaden the combinatorial space and biological phenomenon that polymer microarrays can explore, and increase their efficacy. This will, in turn, facilitate the discovery of optimised polymeric materials for many biomaterial applications.
Publisher: American Vacuum Society
Date: 06-02-2015
DOI: 10.1116/1.4906484
Abstract: The complexity of hyperspectral time of flight secondary ion mass spectrometry (ToF-SIMS) datasets makes their subsequent analysis and interpretation challenging, and is often an impasse to the identification of trends and differences within large s le-sets. The application of multivariate data analysis has become a routine method to successfully deconvolute and analyze objectively these datasets. The advent of high-resolution large area ToF-SIMS imaging capability has enlarged further the data handling challenges. In this work, a modified multivariate curve resolution image analysis of a polymer microarray containing 70 different poly(meth)acrylate type spots (over a 9.2 × 9.2 mm area) is presented. This analysis distinguished key differences within the polymer library such as the differentiation between acrylate and methacrylate polymers and variance specific to side groups. Partial least squares (PLS) regression analysis was performed to identify correlations between the ToF-SIMS surface chemistry and the protein adsorption. PLS analysis identified a number of chemical moieties correlating with high or low protein adsorption, including ions derived from the polymer backbone and polyethylene glycol side-groups. The retrospective validation of the findings from the PLS analysis was also performed using the secondary ion images for those ions found to significantly contribute to high or low protein adsorption.
Publisher: Wiley
Date: 15-05-2012
DOI: 10.1002/SIA.5042
Publisher: Wiley
Date: 22-05-2012
DOI: 10.1002/SIA.5040
Publisher: American Chemical Society (ACS)
Date: 05-07-2017
Publisher: Wiley
Date: 04-12-2013
Publisher: Wiley
Date: 19-10-2020
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.BIOMATERIALS.2021.121350
Abstract: Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for eluting antibiotics or coatings. Candidate monomers were formulated and their processability and reliability demonstrated. Formulations for in vivo evaluation of the 3D printed structures were selected on the basis of their in vitro bacterial biofilm inhibitory properties and lack of mammalian cell cytotoxicity. In vivo in a mouse implant infection model, Pseudomonas aeruginosa biofilm formation on poly-TCDMDA was reduced by ∼99% when compared with medical grade silicone. Whole mouse bioluminescence imaging and tissue immunohistochemistry revealed the ability of the printed device to modulate host immune responses as well as preventing biofilm formation on the device and infection of the surrounding tissues. Since 3D printing can be used to manufacture devices for both prototyping and clinical use, the versatility of ink-jet based 3D-printing to create personalised functional medical devices is demonstrated by the biofilm resistance of both a finger joint prosthetic and a prostatic stent printed in poly-TCDMDA towards P. aeruginosa and Staphylococcus aureus.
Publisher: American Vacuum Society
Date: 11-2020
DOI: 10.1116/6.0000586
Abstract: The emergence of SARS-CoV-2 highlights the global need for platform technologies to enable the rapid development of diagnostics, vaccines, treatments, and personal protective equipment (PPE). However, many current technologies require the detailed mechanistic knowledge of specific material-virion interactions before they can be employed, for ex le, to aid in the purification of vaccine components or in the design of a more effective PPE. Here, we show that an adaption of a polymer microarray method for screening bacterial-surface interactions allows for the screening of polymers for desirable material-virion interactions. Nonpathogenic virus-like particles including fluorophores are exposed to the arrays in an aqueous buffer as a simple model of virions carried to the surface in saliva/sputum. Competitive binding of Lassa and Rubella virus-like particles is measured to probe the relative binding properties of a selection of copolymers. This provides the first step in the development of a method for the discovery of novel materials with promise for viral binding, with the next being development of this method to assess absolute viral adsorption and assessment of the attenuation of the activity of live virus, which we propose would be part of a material scale up step carried out in high containment facilities, alongside the use of more complex media to represent biological fluids.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9RE00173E
Abstract: A novel single-well prototype high throughput microwave reactor geometry has been produced and shown to be capable of synthesizing an array of non-commercially available methacrylate monomers.
Publisher: American Vacuum Society
Date: 05-2023
DOI: 10.1116/6.0002604
Abstract: Secondary ion mass spectrometry (SIMS) offers advantages over both liquid extraction mass spectrometry and matrix assisted laser desorption mass spectrometry in that it provides the direct in situ analysis of molecules and has the potential to preserve the 3D location of an analyte in a s le. Polysaccharides are recognized as challenging analytes in the mass spectrometry of liquids and are also difficult to identify and assign using SIMS. Psl is an exopolysaccharide produced by Pseudomonas aeruginosa, which plays a key role in biofilm formation and maturation. In this Letter, we describe the use of the OrbiTrap analyzer with SIMS (3D OrbiSIMS) for the label-free mass spectrometry of Psl, taking advantage of its high mass resolving power for accurate secondary ion assignment. We study a P. aeruginosa biofilm and compare it with purified Psl to enable the assignment of secondary ions specific to the Psl structure. This resulted in the identification of 17 peaks that could confidently be ascribed to Psl fragments within the biofilm matrix. The complementary approach of the following neutral loss sequences is also shown to identify multiple oligosaccharide fragments without the requirement of a biological reference s le.
Publisher: Wiley
Date: 28-04-2020
Publisher: Wiley
Date: 08-03-2012
DOI: 10.1002/SIA.4910
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.JCONREL.2014.06.045
Abstract: 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.
Publisher: American Society for Microbiology
Date: 29-10-2019
DOI: 10.1128/MSYSTEMS.00390-19
Abstract: We have established a methodology to enable the movement of in idual bacterial cells to be followed within a 3D space without requiring any labeling. Such an approach is important to observe and understand how bacteria interact with surfaces and form biofilm. We investigated the swimming behavior of Pseudomonas aeruginosa , which has two flagellar stators that drive its swimming motion. Mutants that had only either one of the two stators swam slower and were unable to adjust to the near-surface environment as effectively as the wild type. These results are consistent with the mot stators playing key roles in responding to the near-surface environment and could be used by bacteria to sense via their flagella when they are near a surface.
Publisher: American Chemical Society (ACS)
Date: 31-08-2021
Abstract: We report the first successful combination of three distinct high-throughput techniques to deliver the accelerated design, synthesis, and property screening of a library of novel, bio-instructive, polymeric, comb-graft surfactants. These three-dimensional, surface-active materials were successfully used to control the surface properties of particles by forming a unimolecular deep layer on the surface of the particles via microfluidic processing. This strategy deliberately utilizes the surfactant to both create the stable particles and deliver a desired cell-instructive behavior. Therefore, these specifically designed, highly functional surfactants are critical to promoting a desired cell response. This library contained surfactants constructed from 20 molecularly distinct (meth)acrylic monomers, which had been pre-identified by HT screening to exhibit specific, varied, and desirable bacterial biofilm inhibitory responses. The surfactant's self-assembly properties in water were assessed by developing a novel, fully automated, HT method to determine the critical aggregation concentration. These values were used as the input data to a computational-based evaluation of the key molecular descriptors that dictated aggregation behavior. Thus, this combination of HT techniques facilitated the rapid design, generation, and evaluation of further novel, highly functional, cell-instructive surfaces by application of designed surfactants possessing complex molecular architectures.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2012
DOI: 10.1038/NBT.2316
Publisher: American Chemical Society (ACS)
Date: 04-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2JM34782B
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Morgan Alexander.