Imperial College London

Professor Molly Stevens FREng

Faculty of EngineeringDepartment of Materials

Prof of Biomedical Materials&Regenerative Medicine
 
 
 
//

Contact

 

+44 (0)20 7594 6804m.stevens

 
 
//

Location

 

208Royal School of MinesSouth Kensington Campus

//

Summary

 

Publications

Publication Type
Year
to

357 results found

Morez CY, Noseda M, Abreu Paiva M, Belian E, Schneider MD, Stevens MMet al., 2015, Enhanced efficiency of genetic programming toward cardiomyocyte creation through topographical cues, Biomaterials, Vol: 70, Pages: 94-104, ISSN: 1878-5905

Generation of de novo cardiomyocytes through viral over-expression of key transcription factors represents a highly promising strategy for cardiac muscle tissue regeneration. Although the feasibility of cell reprogramming has proven possible both in vitro and in vivo, the efficiency of the process remains extremely low. Here, we report a chemical-free technique in which topographical cues, more specifically parallel microgrooves, enhance the trans-differentiation of cardiac progenitors into cardiomyocyte-like cells. Using a lentivirus-mediated direct reprogramming strategy for expression of Myocardin, Tbx5, and Mef2c, we showed that the microgrooved substrate provokes an increase in histone H3 acetylation (AcH3), known to be a permissive environment for reprogramming by “stemness” factors, as well as stimulation of myocardin sumoylation, a post-translational modification essential to the transcriptional function of this key co-activator. These biochemical effects mimicked those of a pharmacological histone deacetylase inhibitor, valproic acid (VPA), and like VPA markedly augmented the expression of cardiomyocyte-specific proteins by the genetically engineered cells. No instructive effect was seen in cells unresponsive to VPA. In addition, the anisotropy resulting from parallel microgrooves induced cellular alignment, mimicking the native ventricular myocardium and augmenting sarcomere organization.

Journal article

Soh JH, Lin Y, Rana S, Ying JY, Stevens MMet al., 2015, Colorimetric detection of small molecules in complex matrixes via target-mediated growth of aptamer-functionalized gold nanoparticles., Analytical Chemistry, Vol: 87, Pages: 7644-7652, ISSN: 0003-2700

A versatile and sensitive colorimetric assay that allows the rapid detection of small-molecule targets using the naked eye is demonstrated. The working principle of the assay integrates aptamer-target recognition and the aptamer-controlled growth of gold nanoparticles (Au NPs). Aptamer-target interactions modulate the amount of aptamer strands adsorbed on the surface of aptamer-functionalized Au NPs via desorption of the aptamer strands when target molecules bind with the aptamer. Depending on the resulting aptamer coverage, Au NPs grow into morphologically varied nanostructures, which give rise to different colored solutions. Au NPs with low aptamer coverage grow into spherical NPs, which produce red-colored solutions, whereas Au NPs with high aptamer coverage grow into branched NPs, which produce blue-colored solutions. We achieved visible colorimetric response and nanomolar detection limits for the detection of ochratoxin A (1 nM) in red wine samples, as well as cocaine (1 nM) and 17β-estradiol (0.2 nM) in spiked synthetic urine and saliva, respectively. The detection limits were well within clinically and physiologically relevant ranges, and below the maximum food safety limits. The assay is highly sensitive, specific, and able to detect an array of analytes rapidly without requiring sophisticated equipment, making it relevant for many applications, such as high-throughput drug and clinical screening, food sampling, and diagnostics. Furthermore, the assay is easily adapted as a chip-based platform for rapid and portable target detection.

Journal article

Chiappini C, Campagnolo P, Almeida CS, Abbassi-Ghadi N, Chow LW, Hanna GB, Stevens MMet al., 2015, Mapping Local Cytosolic Enzymatic Activity in Human Esophageal Mucosa with Porous Silicon Nanoneedles, Advanced Materials, Vol: 27, Pages: 5147-5152, ISSN: 1521-4095

Porous silicon nanoneedles can map Cathepsin B activity across normal and tumor human esophageal mucosa. Assembling a peptide-based Cathepsin B cleavable sensor over a large array of nano­needles allows the discrimination of cancer cells from healthy ones in mixed culture. The same sensor applied to tissue can map Cathepsin B activity with high resolution across the tumor margin area of esophageal adenocarcinoma.

Journal article

Herrmann IK, Bertazzo S, O'Callaghan D, Schlegel AA, Kallepitis C, Antcliffe D, Gordon A, Stevens MMet al., 2015, Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation, Nanoscale, Vol: 7, Pages: 13511-13520, ISSN: 2040-3364

Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (≤1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions.

Journal article

Mitragotri S, Anderson DG, Chen X, Chow EK, Ho D, Kabanov AV, Karp JM, Kataoka K, Mirkin CA, Petrosko SH, Shi J, Stevens MM, Sun S, Teoh S, Venkatraman SS, Xia Y, Wang S, Gu Z, Xu Cet al., 2015, Accelerating the Translation of Nanomaterials in Biomedicine, Publisher: AMER CHEMICAL SOC

Other

Sinibaldi A, Danz N, Anopchenko A, Munzert P, Schmieder S, Chandrawati R, Rizzo R, Rana S, Sonntag F, Occhicone A, Napione L, De Panfilis S, Stevens MM, Michelotti Fet al., 2015, Label-free detection of tumor angiogenesis biomarker angiopoietin 2 using bloch surface waves on one dimensional photonic crystals, Journal of Lightwave Technology, Vol: 33, Pages: 3385-3393, ISSN: 1558-2213

We describe the design and fabrication of biochips based on 1-D photonic crystals supporting Bloch surface waves for label-free optical biosensing. The optical properties of Bloch surface waves are studied in relation to the geometry of the photonic crystals and on the properties of the dielectric materials used for the fabrication. The planar stacks of the biochips are composed of silica, tantala, and titania that were deposited using plasma-ion-assisted evaporation under high-vacuum conditions. The biochip surfaces were functionalized by silanization, and appropriate fluidic cells were designed to operate in an automated platform. An angularly resolved ellipsometric optical sensing apparatus was assembled to carry out the sensing studies. The angular operation is obtained by a focused laser beam at a fixed wavelength and detection of the angular reflectance spectrum by means of an array detector. The results of the experimental characterization of the physical properties of the fabricated biochips show that their characteristics, in terms of sensitivity and figure of merit, match those expected from the numerical simulations. Practical application of the sensor was demonstrated by detecting a specific glycoprotein, Angio-poietin 2, that is involved in angiogenesis and inflammation processes. The protocol used for the label-free detection of Angiopoietin 2 is described, and the results of an exemplary assay, carried out at a relatively high concentration of 1 μg/ml, are given and confirm that an efficient detection can be achieved. The limit of detection of the biochips for Angiopoietin 2, based on the protocol used, is 1.5 pg/mm2 in buffer solution. The efficiency of the label-free assay is confirmed by independent measurements carried out by means of confocal fluorescence microscopy.

Journal article

Mahat MM, Mawad D, Nelson GW, Fearn S, Palgrave RG, Payne DJ, Stevens MMet al., 2015, Elucidating the deprotonation of polyaniline films by X-ray photoelectron spectroscopy, Journal of Materials Chemistry C, Vol: 3, Pages: 7180-7186, ISSN: 2050-7526

Spin-coated polyaniline (PANI) thin films can be made conductive following treatment with a dopant (reducing or oxidising agent). However, de-doping results in loss of electrical properties. We chemically doped PANI films using p-toluene sulfonic acid (pTSA) and camphor sulfonic acid (CSA) and examined their ability to retain these dopants and their conductive properties in physiological media. Changes in the protonation level of these films were assessed by N 1s core line spectra in X-ray photoelectron spectroscopy (XPS). PANI films were found to de-dope with a decrease in the ratio of N 1s photoelectron signal corresponding to positively charged nitrogen (i.e. –NH2+, [double bond, length as m-dash]NH+) to the total N 1s signal. De-doping of PANI films was confirmed by depletion of the dopant fragment (–SO3−) as determined from both XPS and atomic distribution in Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) images. XPS has been successfully used as a tool to elucidate the deprotonation of PANI films and the loss of the dopant from the bulk.

Journal article

Wang ST, Lin Y, Spicer CD, Stevens MMet al., 2015, Bio-inspired Maillard-Like reactions enable a simple and sensitive assay for colorimetric detection of methylglyoxal., Chemical Communications, Vol: 51, Pages: 11026-11029, ISSN: 1359-7345

A simple and selective assay for detecting methylglyoxal (MGO), a metabolite associated with diabetes, was developed by combining a bio-inspired chemical reaction with the anti-aggregation of gold nanoparticles. This assay could detect MGO at as low as 1 μM by the naked eye and 0.05 μM by UV/vis spectrometry, within the clinical range marking oxidative stress in diabetes, and demonstrated high selectivity over other physiologically relevant ketones and aldehydes.

Journal article

Bertazzo S, Maidment S, Kallepitis C, Fearn S, Stevens MM, Xie HNet al., 2015, Fibres and cellular structures preserved in 75-million–year-old dinosaur specimens, Nature Communications, Vol: 6, ISSN: 2041-1723

Exceptionally preserved organic remains are known throughout the vertebrate fossil record, and recently, evidence has emerged that such soft tissue might contain original components. We examined samples from eight Cretaceous dinosaur bones using nano-analytical techniques; the bones are not exceptionally preserved and show no external indication of soft tissue. In one sample, we observe structures consistent with endogenous collagen fibre remains displaying ~67 nm banding, indicating the possible preservation of the original quaternary structure. Using ToF-SIMS, we identify amino-acid fragments typical of collagen fibrils. Furthermore, we observe structures consistent with putative erythrocyte remains that exhibit mass spectra similar to emu whole blood. Using advanced material characterization approaches, we find that these putative biological structures can be well preserved over geological timescales, and their preservation is more common than previously thought. The preservation of protein over geological timescales offers the opportunity to investigate relationships, physiology and behaviour of long extinct animals.

Journal article

Bell RV, Rochford LA, De Rosales RTM, Stevens M, Weaver JVM, Bon SAFet al., 2015, Fabrication of calcium phosphate microcapsules using emulsion droplets stabilized with branched copolymers as templates, Journal of Materials Chemistry B, Vol: 3, Pages: 5544-5552, ISSN: 2050-750X

We report on a versatile and time-efficient method to fabricate calcium phosphate (CaP) microcapsules by utilizing oil-in-water emulsion droplets stabilized with synthetic branched copolymer (BCP) as templates. The BCP was designed to provide a suitable architecture and functionality to produce stable emulsion droplets, and to permit the mineralization of CaP at the surface of the oil droplet when incubated in a solution containing calcium and phosphate ions. The CaP shells of the microcapsules were established to be calcium deficient hydroxyapatite with incorporated chlorine and carbonate species. These capsule walls were made fluorescent by decoration with a fluorescein-bisphosphonate conjugate.

Journal article

Lin Y, Chapman R, Stevens MM, 2015, Integrative Self-Assembly of Graphene Quantum Dots and Biopolymers into a Versatile Biosensing Toolkit, ADVANCED FUNCTIONAL MATERIALS, Vol: 25, Pages: 3183-3192, ISSN: 1616-301X

Journal article

Parmar PA, Chow LW, St-Pierre J-P, Horejs C-M, Peng YY, Werkmeister JA, Ramshaw JAM, Stevens MMet al., 2015, Collagen-mimetic peptide-modifiable hydrogels for articular cartilage regeneration, BIOMATERIALS, Vol: 54, Pages: 213-225, ISSN: 0142-9612

Journal article

Quinlan E, Partap S, Azevedo MM, Jell G, Stevens MM, O'Brien FJet al., 2015, Hypoxia-mimicking bioactive glass/collagen glycosaminoglycan composite scaffolds to enhance angiogenesis and bone repair, BIOMATERIALS, Vol: 52, Pages: 358-366, ISSN: 0142-9612

Journal article

Campagnolo P, Tsai TN, Hong X, Kirton JP, So PW, Margariti A, Di Bernardini E, Wong MM, Hu Y, Stevens MM, Xu Qet al., 2015, c-Kit+ progenitors generate vascular cells for tissue-engineered grafts through modulation of the Wnt/Klf4 pathway., Biomaterials, Vol: 60, Pages: 53-61, ISSN: 1878-5905

The development of decellularised scaffolds for small diameter vascular grafts is hampered by their limited patency, due to the lack of luminal cell coverage by endothelial cells (EC) and to the low tone of the vessel due to absence of a contractile smooth muscle cells (SMC). In this study, we identify a population of vascular progenitor c-Kit+/Sca-1- cells available in large numbers and derived from immuno-privileged embryonic stem cells (ESCs). We also define an efficient and controlled differentiation protocol yielding fully to differentiated ECs and SMCs in sufficient numbers to allow the repopulation of a tissue engineered vascular graft. When seeded ex vivo on a decellularised vessel, c-Kit+/Sca-1-derived cells recapitulated the native vessel structure and upon in vivo implantation in the mouse, markedly reduced neointima formation and mortality, restoring functional vascularisation. We showed that Krüppel-like transcription factor 4 (Klf4) regulates the choice of differentiation pathway of these cells through β-catenin activation and was itself regulated by the canonical Wnt pathway activator lithium chloride. Our data show that ESC-derived c-Kit+/Sca-1-cells can be differentiated through a Klf4/β-catenin dependent pathway and are a suitable source of vascular progenitors for the creation of superior tissue-engineered vessels from decellularised scaffolds.

Journal article

Fuhrmann G, Serio A, Mazo M, Nair R, Stevens MMet al., 2015, Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins, Journal of Controlled Release, Vol: 205, Pages: 35-44, ISSN: 1873-4995

Extracellular vesicles (EVs) are phospholipid-based particles endogenously produced by cells. Their natural composition and selective cell interactions make them promising drug carriers. However, in order to harness their properties, efficient exogenous drug encapsulation methods need to be investigated. Here, EVs from various cellular origins (endothelial, cancer and stem cells) were produced and characterised for size and composition. Porphyrins of different hydrophobicities were employed as model drugs and encapsulated into EVs using various passive and active methods (electroporation, saponin, extrusion and dialysis). Hydrophobic compounds loaded very efficiently into EVs and at significantly higher amounts than into standard liposomes composed of phosphocholine and cholesterol using passive incubation. Moreover, loading into EVs significantly increased the cellular uptake by > 60% and the photodynamic effect of hydrophobic porphyrins in vitro compared to free or liposome encapsulated drug. The active encapsulation techniques, with the saponin-assisted method in particular, allowed an up to 11 fold higher drug loading of hydrophilic porphyrins compared to passive methods. EVs loaded with hydrophilic porphyrins induced a stronger phototoxic effect than free drug in a cancer cell model. Our findings create a firm basis for the development of EVs as smart drug carriers based on straightforward and transferable methods.

Journal article

Fuhrmann G, Herrman IK, Stevens MM, 2015, Cell-derived vesicles for drug therapy and diagnostics: Opportunities and challenges, Nano Today, Vol: 10, Pages: 397-409, ISSN: 1748-0132

Extracellular vesicles are small lipid-based membrane-bound entities shed by cells under both physiological and pathological conditions. Their discovery as intercellular communicators through transfer of nucleic acid- and protein-based cargos between cells locally and at distance in a highly specific manner has created recent excitement. The information they transport and their composition may vary depending on the cell of origin as well as the eliciting stimulus. Such sensitive changes in vesicle characteristics hold significant promise for the improved diagnosis of pathological conditions, including infections and neoplastic lesions in a minimally invasive way. Similarly, these cell-derived vesicles exhibit promising characteristics that could enhance drug targeting efficiencies. Recent developments in the field have aimed at studying EVs as novel drug carriers due to their natural composition, biological function and selective cell interaction. In this review, we discuss new research avenues in diagnostics and drug therapy based on extracellular vesicles. We show how cell-derived vesicles can be harvested and engineered to meet application-specific design requirements. We finally discuss potential risks encountered when translating extracellular vesicle based approaches into (pre)clinical applications.

Journal article

Danz N, Sinibaldi A, Munzert P, Anopchenko O, Förster E, Schmieder S, Chandrawati R, Rizzo R, Heller R, Sonntag F, Mascioletti A, Rana S, Schubert T, Stevens MM, Michelott Fet al., 2015, Biosensing platform combining label-free and labelled analysis using Bloch surface waves, Proceedings of SPIE, Vol: 9506, ISSN: 1996-756X

Journal article

Chiappini C, Martinez JO, De Rosa E, Almeida CS, Tasciotti E, Stevens MMet al., 2015, Biodegradable nanoneedles for localized delivery of nanoparticles in vivo: Exploring the biointerface, ACS Nano, Vol: 9, Pages: 5500-5509, ISSN: 1936-0851

Journal article

Chiappini C, De Rosa E, Martinez JO, Liu X, Steele J, Stevens MM, Tasciotti Eet al., 2015, Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization., Nature Materials, Vol: 14, Pages: 532-539, ISSN: 1476-4660

The controlled delivery of nucleic acids to selected tissues remains an inefficient process mired by low transfection efficacy, poor scalability because of varying efficiency with cell type and location, and questionable safety as a result of toxicity issues arising from the typical materials and procedures employed. High efficiency and minimal toxicity in vitro has been shown for intracellular delivery of nuclei acids by using nanoneedles, yet extending these characteristics to in vivo delivery has been difficult, as current interfacing strategies rely on complex equipment or active cell internalization through prolonged interfacing. Here, we show that a tunable array of biodegradable nanoneedles fabricated by metal-assisted chemical etching of silicon can access the cytosol to co-deliver DNA and siRNA with an efficiency greater than 90%, and that in vivo the nanoneedles transfect the VEGF-165 gene, inducing sustained neovascularization and a localized sixfold increase in blood perfusion in a target region of the muscle.

Journal article

Volk H-D, Stevens MM, Mooney DJ, Grainger DW, Duda GNet al., 2015, Key elements for nourishing the translational research environment, Science Translational Medicine, Vol: 7, ISSN: 1946-6242

Journal article

Autefage H, Gentleman E, Littmann E, Hedegaard MAB, Von Erlach T, O'Donnell M, Burden FR, Winkler DA, Stevens MMet al., 2015, Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 112, Pages: 4280-4285, ISSN: 0027-8424

Journal article

Chapman R, Lin Y, Burnapp M, Bentham A, Hillier D, Zabron A, Khan S, Tyreman M, Stevens MMet al., 2015, Multivalent nanoparticle networks enable point-of-care detection of human phospholipase-A2 in serum, ACS Nano, Vol: 9, Pages: 2565-2573, ISSN: 1936-086X

Journal article

Hembury M, Chiappini C, Bertazzo S, Kalber TL, Drisko GL, Ogunlade O, Walker-Samuel S, Krishna KS, Jumeaux C, Beard P, Kumar CSSR, Porter AE, Lythgoe MF, Boissiere C, Sanchez C, Stevens MMet al., 2015, Gold-silica quantum rattles for multimodal imaging and therapy, Proceedings of the National Academy of Sciences, Vol: 112, Pages: 1959-1964, ISSN: 1091-6490

Gold quantum dots exhibit distinctive optical and magnetic behaviors compared with larger gold nanoparticles. However, their unfavorable interaction with living systems and lack of stability in aqueous solvents has so far prevented their adoption in biology and medicine. Here, a simple synthetic pathway integrates gold quantum dots within a mesoporous silica shell, alongside larger gold nanoparticles within the shell’s central cavity. This “quantum rattle” structure is stable in aqueous solutions, does not elicit cell toxicity, preserves the attractive near-infrared photonics and paramagnetism of gold quantum dots, and enhances the drug-carrier performance of the silica shell. In vivo, the quantum rattles reduced tumor burden in a single course of photothermal therapy while coupling three complementary imaging modalities: near-infrared fluorescence, photoacoustic, and magnetic resonance imaging. The incorporation of gold within the quantum rattles significantly enhanced the drug-carrier performance of the silica shell. This innovative material design based on the mutually beneficial interaction of gold and silica introduces the use of gold quantum dots for imaging and therapeutic applications.

Journal article

von Erlach TC, Hedegaard MAB, Stevens MM, 2015, High resolution Raman spectroscopy mapping of stem cell micropatterns, ANALYST, Vol: 140, Pages: 1798-1803, ISSN: 0003-2654

Journal article

Jumeaux C, Chapman R, Chandrawati R, Stevens MMet al., 2015, Synthesis and self-assembly of temperature-responsive copolymers based on N-vinylpyrrolidone and triethylene glycol methacrylate, POLYMER CHEMISTRY, Vol: 6, Pages: 4116-4122, ISSN: 1759-9954

Journal article

Azevedo MM, Tsigkou O, Nair R, Jones JR, Jell G, Stevens MMet al., 2015, Hypoxia Inducible Factor-Stabilizing Bioactive Glasses for Directing Mesenchymal Stem Cell Behavior, TISSUE ENGINEERING PART A, Vol: 21, Pages: 382-389, ISSN: 1937-3341

Journal article

Chan WCW, Gogotsi Y, Hafner JH, Hammond PT, Hersam MC, Javey A, Kagan CR, Khademhosseini A, Kotov NA, Lee S-T, Möhwald H, Mulvaney PA, Nel AE, Nordlander PJ, Parak WJ, Penner RM, Rogach AL, Schaak RE, Stevens MM, Wee ATS, Willson CG, Weiss PSet al., 2014, A year for nanoscience., ACS Nano, Vol: 8, Pages: 11901-11903

Journal article

Duda GN, Grainger DW, Frisk ML, Bruckner-Tuderman L, Carr A, Dirnagl U, Einhaeupl KM, Gottschalk S, Gruskin E, Huber C, June CH, Mooney DJ, Rietschel ET, Schuette G, Seeger W, Stevens MM, Urban R, Veldman A, Wess G, Volk H-Det al., 2014, Changing the Mindset in Life Sciences Toward Translation: A Consensus, SCIENCE TRANSLATIONAL MEDICINE, Vol: 6, ISSN: 1946-6234

Journal article

Chapman R, Gormley AJ, Herpoldt K-L, Stevens MMet al., 2014, Highly controlled open vessel RAFT polymerizations byenzyme degassing, Macromolecules, Vol: 47, Pages: 8541-8547, ISSN: 0024-9297

Journal article

Gormley AJ, Chapman R, Stevens MM, 2014, Polymerization amplified detection for nanoparticle-based biosensing, Nano Letters, Vol: 14, Pages: 6368-6373, ISSN: 1530-6992

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: id=00398347&limit=30&person=true&page=6&respub-action=search.html