Publications by authors named "Brougham D"

Magnetic chromatography was exploited to fractionate suspensions of magnetoliposomes (SML: lumen-free lipid-encapsulated clusters of multiple magnetic iron-oxide nanoparticles) improving their colloidal properties and relaxivity (magnetic resonance image contrast capability). Fractionation (i) removed sub-populations that do not contribute to the MRI response, and thus (ii) enabled evaluation of the size-dependence of relaxivity for the MRI-active part, which was surprisingly weak in the 55-90 nm range. MC was therefore implemented for processing multiple PEGylated SML types having average sizes ranging from 85 to 105 nm, which were then shown to have strongly size-dependent uptake in an pancreatic cancer model.

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The influence of surfactant, cross-linker, and initiator on the final structure and thermoresponse of poly(-isopropylmethacrylamide) (pNIPMAM) microgels was evaluated. The goals were to control particle size (into the nanorange) and transition temperature (across the physiologically accessible range). The concentration of the reactants used in the synthesis was varied, except for the monomer, which was kept constant.

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  • Recent advances in converting somatic cells into induced Pluripotent Stem Cells (iPSCs) have led to the development of kidney organoids for studying kidney development and disease.
  • Significant progress has been made by applying renal developmental signaling pathways and using hydrogel scaffolds like self-assembling peptide hydrogels (SAPHs) and gelatin methacryloyl (GelMA) for growing these organoids.
  • This work outlines methods to generate human iPSC-derived kidney organoids, their maturation in hydrogels, and protocols for characterizing these organoids through immunofluorescence imaging.
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Osteoarthritis (OA) is the most common form of arthritis, with intra-articular (IA) delivery of therapeutics being the current best option to treat pain and inflammation. However, IA delivery is challenging due to the rapid clearance of therapeutics from the joint and the need for repeated injections. Thus, there is a need for long-acting delivery systems that increase the drug retention time in joints with the capacity to penetrate OA cartilage.

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  • Researchers created a library of composite polymer networks (CPNs) by mixing Pluronic F127 with various di-acrylate functionalized PEG polymers, focusing on how these combinations affect properties like viscosity and UV crosslinking.
  • A phase diagram was developed to understand how the varying PEG compositions affect micelle behavior and contribute to the material's liquefaction.
  • The study also explored how different compositions influenced 3D printing, revealing that micelle content significantly impacted printing quality, and UV crosslinking enhanced the structural integrity of the hydrogels.
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Responsive magnetic nanomaterials offer significant advantages for innovative therapies, for instance, in cancer treatments that exploit on-demand delivery on alternating magnetic field (AMF) stimulus. In this work, biocompatible magnetic bionanocomposite films are fabricated from chitosan by film casting with incorporation of magnetite nanoparticles (MNPs) produced by facile one pot synthesis. The influence of synthesis conditions and MNP concentration on the films' heating efficiency and heat dissipation are evaluated through spatio-temporal mapping of the surface temperature changes by video-thermography.

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A Brownian shell model describing the random rotational motion of a spherical shell of uniform particle density is presented and validated by molecular dynamics simulations. The model is applied to proton spin rotation in aqueous paramagnetic ion complexes to yield an expression for the Larmor-frequency-dependent nuclear magnetic resonance spin-lattice relaxation rate T_{1}^{-1}(ω) describing the dipolar coupling of the nuclear spin of the proton with the electronic spin of the ion. The Brownian shell model provides a significant enhancement to existing particle-particle dipolar models without added complexity, allowing fits to experimental T_{1}^{-1}(ω) dispersion curves without arbitrary scaling parameters.

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Phenylboronic acids (BAs) are important synthetic receptors that bind reversibly to cis-diols enabling their use in molecular sensing. When conjugated to magnetic iron oxide nanoparticles, BAs have potential for application in separations and enrichment. Realizing this will require a new understanding of their inherent binding modes and measurement of their binding capacity and their stability in/extractability from complex environments.

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Spinal cord injury (SCI) is a devastating condition with no curative therapy currently available. Immunomodulation can be applied as a therapeutic strategy to drive alternative immune cell activation and promote a proregenerative injury microenvironment. Locally injected hydrogels carrying immunotherapeutic cargo directly to injured tissue offer an encouraging treatment approach from an immunopharmacological perspective.

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Superparamagnetic iron oxide nanoparticles, MNPs, are under investigation as stimulus-responsive nanocarriers that can be tracked by magnetic resonance imaging. However, fundamental questions remain, including the effect of differing surface chemistries on MR image contrast efficacy (relaxivity), both initially and over time in the biological environment. The effects of pH and ligand type on the relaxivity of electrostatically and sterically stabilized spherical 8.

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Nanocarriers are candidates for cancer chemotherapy delivery, with growing numbers of clinically-approved nano-liposomal formulations such as Doxil® and Onivyde® (liposomal doxorubicin and irinotecan) providing proof-of-concept. However, their complex biodistribution and the varying susceptibility of individual patient tumours to nanoparticle deposition remains a clinical challenge. Here we describe the preparation, characterisation, and biological evaluation of phospholipidic structures containing solid magnetic cores (SMLs) as an MRI-trackable surrogate that could aid in the clinical development and deployment of nano-liposomal formulations.

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Magnetic iron oxide nanoparticles have multiple biomedical applications in AC-field hyperthermia and magnetic resonance imaging (MRI) contrast enhancement. Here, two cubic particle suspensions are analyzed in detail, one suspension displayed strong magnetic heating and MRI contrast efficacies, while the other responded weakly. This is despite them having almost identical size, morphology, and colloidal dispersion.

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  • TGFβ1 regulates kidney cell fate and fibrosis progression.
  • SMAD3 and EZH2 co-occupy specific genomic regions in kidney stem cells and their derivatives.
  • Inhibiting EZH2 disrupts SMAD3 activity and prevents myofibroblast activation, highlighting a key mechanism in kidney fibrosis.
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Multifunctional nanocomposites which exhibit well-defined physical properties and encode spatiotemporally-controlled responses are emerging as components for advanced responsive systems. For biomedical applications magnetic nanocomposite materials have attracted significant attention due to their ability to respond to spatially and temporally varying magnetic fields. The current state-of-the-art in development and fabrication of magnetic hydrogels toward biomedical applications is described.

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Superparamagnetic iron oxide nanoparticles (SPIONs) are a contaminant of emerging interest, often used in the medical field as an imaging contrast agent, with additional uses in wastewater treatment and as food additives. Although the use of SPIONs is increasing, little research has been conducted on the toxic impacts to living organisms beyond traditional lethal concentration endpoints. Daphnia magna are model organisms for aquatic toxicity testing with a well understood metabolome and high sensitivity to SPIONs.

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  • Human induced pluripotent stem cell (hiPSC)-derived kidney organoids show promise for disease modeling and personalized medicine, but improvements in their formation methods are needed.* -
  • Researchers matured these organoids in synthetic self-assembling peptide hydrogels (SAPHs) with varying stiffness, achieving structures similar to those grown in traditional animal-derived matrices like Matrigel.* -
  • Analysis revealed that organoids developed in higher stiffness SAPHs had more mature podocyte gene expressions and fewer off-target cell types, highlighting the benefits of using synthetic hydrogels for kidney organoid maturation.*
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Multicore magnetic iron oxide nanoparticles, nanoflowers (NFs), have potential biomedical applications as efficient mediators for AC-magnetic field hyperthermia and as contrast agents for magnetic resonance imaging due to their strong magnetic responses arising from complex internal magnetic ordering. To realise these applications amenable surface chemistry must be engineered that maintain particle dispersion. Here a catechol-derived grafting approach is described to strongly bind polyethylene glycol (PEG) to NFs and provide stable hydrogen-bonded hydrated layers that ensure good long-term colloidal stability in buffers and media even at clinical MRI field strength and high concentration.

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  • Vitamin D deficiency is a widespread problem, and using food fortification strategies, like mixed micelles (MM), could help combat this issue by improving vitamin D absorption.
  • The study compared different delivery systems, finding that emulsions (using olive or coconut oil) and MM based systems had varying levels of vitamin D bioaccessibility during digestion, with MM generally performing better.
  • Results showed that MM systems led to higher vitamin D bioaccessibility (around 90-93%) compared to oil-in-water emulsions (75-78%), suggesting that MM could be an effective delivery method for enhancing vitamin D in food.
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  • Extracellular vesicles (EVs) are tiny particles that transport biological materials in the body and have been extensively studied under the MISEV framework for standardizing research in this area since 2018.
  • Research has primarily focused on human EVs, but there's growing interest in applying the same standards to animal models, particularly felines, for comparative disease studies.
  • The study found that EVs isolated from healthy humans and felines shared similar characteristics, suggesting that the MISEV guidelines can be effectively applied to feline EV research, potentially benefiting our understanding of diseases in both species.
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Hydrogels loaded with magnetic iron oxide nanoparticles that can be patterned and which controllably induce hyperthermic responses on AC-field stimulation are of interest as functional components of next-generation biomaterials. Formation of nanocomposite hydrogels is known to eliminate any Brownian contribution to hyperthermic response (reducing stimulated heating) while the Néel contribution can also be suppressed by inter-particle dipolar interactions arising from aggregation induced before or during gelation. We describe the ability of graphene oxide (GO) flakes to restore the hyperthermic efficiency of soft printable hydrogels formed using Pluronics F127 and PEGylated magnetic nanoflowers.

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Spinal cord injury (SCI) is a complex medical and psychological challenge for which there is no curative therapy currently available. Despite major progress in pharmacological and surgical approaches, clinical trials for SCI patients have been uniformly disappointing thus far as there are many practical and biological issues yet to be resolved. Neuroinflammation is a critical event of the secondary injury phase after SCI, and recent research strategies have focused on modulating the immune response after injury to provide a more favorable recovery environment.

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Deficiency of vitamin-D is prevalent globally and can lead to negative health consequences. The fat-soluble nature of vitamin-D, coupled with its sensitivity to heat, light and oxygen limits its incorporation into foods. Mixed micelles (MM) have potential to enhance bioavailability of vitamin-D.

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Polyethylene glycol grafting has played a central role in preparing the surfaces of nano-probes for biological interaction, to extend blood circulation times and to modulate protein recognition and cellular uptake. However, the role of PEG graft dynamics and conformation in determining surface recognition processes is poorly understood primarily due to the absence of a microscopic picture of the surface presentation of the polymer. Here a detailed NMR analysis reveals three types of dynamic ethylene glycol units on PEG-grafted SiO2 nanoparticles (NPs) of the type commonly evaluated as long-circulating theranostic nano-probes; a narrow fraction with fast dynamics associated with the chain ends; a broadened fraction spectrally overlapped with the former arising from those parts of the chain experiencing some dynamic restriction; and a fraction too broad to be observed in the spectrum arising from units closer to the surface/graft which undergo slow motion on the NMR timescale.

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Correction for 'Electrostatically modulated magnetophoretic transport of functionalised iron-oxide nanoparticles through hydrated networks' by Stephen Lyons et al., Nanoscale, 2020, 12, 10550-10558, DOI: 10.1039/D0NR01602K.

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  • The study establishes rules for heat induction based on factors such as particle concentration and gel volume, achieving temperature jumps of 0-12°C within 10 minutes, and compares heat response in "closed" and "open" systems.
  • It also shows how 3D printing can control the spatial distribution of heat in the hydrogels, demonstrating localized heat induction for the controlled release of molecules, which has potential applications in regenerative medicine.
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