Imperial College London

Professor Molly Stevens FREng

Faculty of EngineeringDepartment of Materials

Prof of Biomedical Materials&Regenerative Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6804m.stevens

 
 
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Location

 

208Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

348 results found

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

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

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

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

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

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

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

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

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

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

Howes PD, Chandrawati R, Stevens MM, 2014, Colloidal nanoparticles as advanced biological sensors, Science, Vol: 346, ISSN: 0036-8075

Colloidal nanoparticle biosensors have received intense scientific attention and offer promising applications in both research and medicine. We review the state of the art in nanoparticle development, surface chemistry, and biosensing mechanisms, discussing how a range of technologies are contributing toward commercial and clinical translation. Recent examples of success include the ultrasensitive detection of cancer biomarkers in human serum and in vivo sensing of methyl mercury. We identify five key materials challenges, including the development of robust mass-scale nanoparticle synthesis methods, and five broader challenges, including the use of simulations and bioinformatics-driven experimental approaches for predictive modeling of biosensor performance. The resultant generation of nanoparticle biosensors will form the basis of high-performance analytical assays, effective multiplexed intracellular sensors, and sophisticated in vivo probes.

Journal article

Smith EL, Kanczler JM, Gothard D, Roberts CA, Wells JA, White LJ, Qutachi O, Sawkins MJ, Peto H, Rashidi H, Rojo L, Stevens MM, El Haj AJ, Rose FRAJ, Shakesheff KM, Oreffo ROCet al., 2014, Evaluation of skeletal tissue repair, Part 1: Assessment of novel growth-factor-releasing hydrogels in an ex vivo chick femur defect model, ACTA BIOMATERIALIA, Vol: 10, Pages: 4186-4196, ISSN: 1742-7061

Journal article

Smith EL, Kanczler JM, Gothard D, Roberts CA, Wells JA, White LJ, Qutachi O, Sawkins MJ, Peto H, Rashidi H, Rojo L, Stevens MM, El Haj AJ, Rose FRAJ, Shakesheff KM, Oreffo ROCet al., 2014, Evaluation of skeletal tissue repair, Part 2: Enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model, ACTA BIOMATERIALIA, Vol: 10, Pages: 4197-4205, ISSN: 1742-7061

Journal article

de la Rica R, Chow LW, Horejs C-M, Mazo M, Chiappini C, Pashuck ET, Bitton R, Stevens MMet al., 2014, A designer peptide as a template for growing Au nanoclusters, CHEMICAL COMMUNICATIONS, Vol: 50, Pages: 10648-10650, ISSN: 1359-7345

Journal article

Xie H-N, Lin Y, Mazo M, Chiappini C, Sanchez-Iglesias A, Liz-Marzan LM, Stevens MMet al., 2014, Identification of intracellular gold nanoparticles using surface-enhanced Raman scattering, Nanoscale, Vol: 6, Pages: 12403-12407, ISSN: 2040-3364

The identification of intracellular distributions of noble metal nanoparticles is of great utility for many biomedical applications. We present an effective method to distinguish intracellular from extracellular nanoparticles by selectively quenching the SERS signals from dye molecules adsorbed onto star-shaped gold nanoparticles that have not been internalized by cells.

Journal article

Ren J, Blackwood KA, Doustgani A, Poh PP, Steck R, Stevens MM, Woodruff MAet al., 2014, Melt-electrospun polycaprolactone strontium-substituted bioactive glass scaffolds for bone regeneration, JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, Vol: 102, Pages: 3140-3153, ISSN: 1549-3296

Journal article

Su L, Cloyd KL, Arya S, Hedegaard MAB, Steele JAM, Elson DS, Stevens MM, Hanna GBet al., 2014, Raman spectroscopic evidence of tissue restructuring in heat-induced tissue fusion, JOURNAL OF BIOPHOTONICS, Vol: 7, Pages: 713-723, ISSN: 1864-063X

Journal article

Chow LW, Armgarth A, St-Pierre JP, Bertazzo S, Gentilini C, Aurisicchio C, McCullen SD, Steele JA, Stevens MMet al., 2014, Biomimetic materials: Peptide-directed spatial organization of biomolecules in dynamic gradient scaffolds (adv. Healthcare mater. 9/2014)., Adv Healthc Mater, Vol: 3

Peptide-polymer conjugates that specifically and dynamically bind glycosaminoglycans are used to functionalize the surface of biodegradable electrospun fiber scaffolds. The versatile platform presented by L. W. Chow, M. M. Stevens, and colleagues on page 1381 can be used to recreate gradients of ECM-like biomolecule organization within scaffolds to achieve more functional and clinically relevant tissue-engineered constructs.

Journal article

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