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

248 results found

Amdursky N, Rashid MH, Stevens MM, Yarovsky Iet al., Exploring the binding sites and proton diffusion on insulin amyloid fibril surface by naphthol-based photoacid fluorescence and molecular simulations, Scientific Reports, ISSN: 2045-2322

JOURNAL ARTICLE

Bergholt M, Albro M, Stevens MM, Online quantitative monitoring of live cell engineered cartilage growth using diffuse fiber-optic Raman spectroscopy, Biomaterials, ISSN: 1878-5905

JOURNAL ARTICLE

Chandrawati R, Olesen MTJ, Marini TCC, Bisra G, Guex AG, De Oliveira MG, Zelikin AN, Stevens MMet al., Enzyme Prodrug Therapy Engineered into Electrospun Fibers with Embedded Liposomes for Controlled, Localized Synthesis of Therapeutics, Advanced Healthcare Materials, ISSN: 2192-2640

JOURNAL ARTICLE

Soh JH, Lin Y, Thomas MR, Todorova N, Kallepitis C, Ying JY, Yarovsky I, Stevens MMet al., Distinct bimodal roles of aromatic molecules in controlling gold nanorod growth for biosensing, Advanced Functional Materials, ISSN: 1616-3028

New aromatic molecule–seed particle interactions are examined and exploited to control and guide seed-mediated gold nanorod (Au NR) growth. This new approach enables better understanding of how small molecules impact the synthesis of metallic nanostructures, catalysing their use in various biomedical applications, such as plasmonic biosensing. We perform experimental studies and theoretical molecular simulations using a library of aromatic molecules where we take advantage of the chemical versatility of the molecules with varied spatial arrangements of electron donating/withdrawing groups, charge, and Au-binding propensity. Au NR growth is regulated by two principal mechanisms, producing either a red or blue shift in the longitudinal localized surface plasmon resonance (LLSPR) peaks. Aromatic molecules with high redox potentials produced an increase in NR aspect ratio and red shift of LLSPR peaks. In contrast, molecules that strongly bind gold surfaces resulted in blue shifts, demonstrating a strong correlation between their binding energy and blue shifts produced. Through enzymatic conversion of selected molecules, 4-aminophenylphosphate to 4-aminophenol, we obtained opposing growth mechanisms at opposite extremes of target concentration, and established a chemical pathway for performing plasmonic ELISA. This unlocks new strategies for tailoring substrate design and enzymatic mechanisms for controlling plasmonic response to target detection in biosensing applications.

JOURNAL ARTICLE

guex AG, Spicer CD, Armgarth A, Gelmi A, Humphrey EJ, Terracciano CM, Harding S, Stevens MMet al., Electrospun aniline-tetramer-co-polycaprolactone fibres for conductive, biodegradable scaffolds, MRS Communications, ISSN: 2159-6867

JOURNAL ARTICLE

Amdursky N, Wang X, Meredith P, Riley DJ, Payne DJ, Bradley DDC, Stevens MMet al., 2017, Electron Hopping Across Hemin-Doped Serum Albumin Mats on Centimeter-Length Scales., Adv Mater

Exploring long-range electron transport across protein assemblies is a central interest in both the fundamental research of biological processes and the emerging field of bioelectronics. This work examines the use of serum-albumin-based freestanding mats as macroscopic electron mediators in bioelectronic devices. In particular, this study focuses on how doping the protein mat with hemin improves charge-transport. It is demonstrated that doping can increase conductivity 40-fold via electron hopping between adjacent hemin molecules, resulting in the highest measured conductance for a protein-based material yet reported, and transport over centimeter length scales. The use of distance-dependent AC impedance and DC current-voltage measurements allows the contribution from electron hopping between adjacent hemin molecules to be isolated. Because the hemin-doped serum albumin mats have both biocompatibility and fabrication simplicity, they should be applicable to a range of bioelectronic devices of varying sizes, configurations, and applications.

JOURNAL ARTICLE

Armstrong JPK, Holme MN, Stevens MM, 2017, Re-Engineering Extracellular Vesicles as Smart Nanoscale Therapeutics, ACS NANO, Vol: 11, Pages: 69-83, ISSN: 1936-0851

JOURNAL ARTICLE

Chandrawati R, Chang JYH, Reina-Torres E, Jumeaux C, Sherwood JM, Stamer WD, Zelikin AN, Overby DR, Stevens MMet al., 2017, Localized and Controlled Delivery of Nitric Oxide to the Conventional Outflow Pathway via Enzyme Biocatalysis: Toward Therapy for Glaucoma, ADVANCED MATERIALS, Vol: 29, ISSN: 0935-9648

JOURNAL ARTICLE

Chang JYH, Chow LW, Dismuke WM, Ethier CR, Stevens MM, Stamer WD, Overby DRet al., 2017, Peptide-Functionalized Fluorescent Particles for In Situ Detection of Nitric Oxide via Peroxynitrite-Mediated Nitration., Adv Healthc Mater

Nitric oxide (NO) is a free radical signaling molecule that plays a crucial role in modulating physiological homeostasis across multiple biological systems. NO dysregulation is linked to the pathogenesis of multiple diseases; therefore, its quantification is important for understanding pathophysiological processes. The detection of NO is challenging, typically limited by its reactive nature and short half-life. Additionally, the presence of interfering analytes and accessibility to biological fluids in the native tissues make the measurement technically challenging and often unreliable. Here, a bio-inspired peptide-based NO sensor is developed, which detects NO-derived oxidants, predominately peroxynitrite-mediated nitration of tyrosine residues. It is demonstrated that these peptide-based NO sensors can detect peroxynitrite-mediated nitration in response to physiological shear stress by endothelial cells in vitro. Using the peptide-conjugated fluorescent particle immunoassay, peroxynitrite-mediated nitration activity with a detection limit of ≈100 × 10(-9) m is detected. This study envisions that the NO detection platform can be applied to a multitude of applications including monitoring of NO activity in healthy and diseased tissues, localized detection of NO production of specific cells, and cell-based/therapeutic screening of peroxynitrite levels to monitor pronitroxidative stress in biological samples.

JOURNAL ARTICLE

Chung JJ, Fujita Y, Li S, Stevens MM, Kasuga T, Georgiou TK, Jones JRet al., 2017, Biodegradable inorganic-organic hybrids of methacrylate star polymers for bone regeneration, ACTA BIOMATERIALIA, Vol: 54, Pages: 411-418, ISSN: 1742-7061

JOURNAL ARTICLE

Chung JJ, Sum BST, Li S, Stevens MM, Georgiou TK, Jones JRet al., 2017, Effect of Comonomers on Physical Properties and Cell Attachment to Silica-Methacrylate/Acrylate Hybrids for Bone Substitution., Macromol Rapid Commun

Hybrids with a silica network covalently bonded to a polymer are promising materials for bone repair. Previous work on synthesizing methyl methacrylate (MMA) based copolymers by reversible addition-fragmentation chain transfer (RAFT) polymerization gives high tailorability of mechanical properties since sophisticated polymer structures can be designed. However, more flexible hybrids would be beneficial. Here, n-butyl methacrylate (BMA) and methyl acrylate (MA) based hybrids are produced. Unlike MMA, BMA and MA hybrids do not show plastic deformation, and BMA hybrid has strain to failure of 33%. Although the new hybrids are more flexible, preosteoblast cells do not adhere on their surfaces, due to higher hydrophobicity and lower stiffness. Comonomer choice is crucial for bone regenerative hybrids.

JOURNAL ARTICLE

Clarke DE, Pashuck ET, Bertazzo S, Weaver JVM, Stevens MMet al., 2017, Self-Healing, Self-Assembled beta-Sheet Peptide Poly(gamma-glutamic acid) Hybrid Hydrogels, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 139, Pages: 7250-7255, ISSN: 0002-7863

JOURNAL ARTICLE

Fiocco L, Li S, Stevens MM, Bernardo E, Jones JRet al., 2017, Biocompatibility and bioactivity of porous polymer-derived Ca-Mg silicate ceramics, ACTA BIOMATERIALIA, Vol: 50, Pages: 56-67, ISSN: 1742-7061

JOURNAL ARTICLE

Hall CE, Yao Z, Choi M, Tyzack GE, Serio A, Luisier R, Harley J, Preza E, Arber C, Crisp SJ, Watson PMD, Kullmann DM, Abramov AY, Wray S, Burley R, Loh SHY, Martins LM, Stevens MM, Luscombe NM, Sibley CR, Lakatos A, Ule J, Gandhi S, Patani Ret al., 2017, Progressive Motor Neuron Pathology and the Role of Astrocytes in a Human Stem Cell Model of VCP-Related ALS, CELL REPORTS, Vol: 19, Pages: 1739-1749, ISSN: 2211-1247

JOURNAL ARTICLE

Higgins SG, Stevens MM, 2017, Extracting the contents of living cells, SCIENCE, Vol: 356, Pages: 379-380, ISSN: 0036-8075

JOURNAL ARTICLE

Horejs C-M, St-Pierre J-P, Ojala JRM, Steele JAM, da Silva PB, Rynne-Vidal A, Maynard SA, Hansel CS, Rodriguez-Fernandez C, Mazo MM, You AYF, Wang AJ, von Erlach T, Tryggvason K, Lopez-Cabrera M, Stevens MMet al., 2017, Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723

JOURNAL ARTICLE

Kallepitis C, Bergholt MS, Mazo MM, Leonardo V, Skaalure SC, Maynard SA, Stevens MMet al., 2017, Quantitative volumetric Raman imaging of three dimensional cell cultures, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723

JOURNAL ARTICLE

Kim E, Howes PD, Crowder SW, Stevens MMet al., 2017, Multi-Amplified Sensing of MicroRNA by a Small DNA Fragment-Driven Enzymatic Cascade Reaction, ACS SENSORS, Vol: 2, Pages: 111-118, ISSN: 2379-3694

JOURNAL ARTICLE

Kim E, Zwi-Dantsis L, Reznikov N, Hansel CS, Agarwal S, Stevens MMet al., 2017, One-Pot Synthesis of Multiple Protein-Encapsulated DNA Flowers and Their Application in Intracellular Protein Delivery., Adv Mater

Inspired by biological systems, many biomimetic methods suggest fabrication of functional materials with unique physicochemical properties. Such methods frequently generate organic-inorganic composites that feature highly ordered hierarchical structures with intriguing properties, distinct from their individual components. A striking example is that of DNA-inorganic hybrid micro/nanostructures, fabricated by the rolling circle technique. Here, a novel concept for the encapsulation of bioactive proteins in DNA flowers (DNF) while maintaining the activity of protein payloads is reported. A wide range of proteins, including enzymes, can be simultaneously associated with the growing DNA strands and Mg2 PPi crystals during the rolling circle process, ultimately leading to the direct immobilization of proteins into DNF. The unique porous structure of this construct, along with the abundance of Mg ions and DNA molecules present, provides many interaction sites for proteins, enabling high loading efficiency and enhanced stability. Further, as a proof of concept, it is demonstrated that the DNF can deliver payloads of cytotoxic protein (i.e., RNase A) to the cells without a loss in its biological function and structural integrity, resulting in highly increased cell death compared to the free protein.

JOURNAL ARTICLE

Lin Y, Pashuck ET, Thomas MR, Amdursky N, Wang S-T, Chow LW, Stevens MMet al., 2017, Plasmonic Chirality Imprinting on Nucleobase-Displaying Supramolecular Nanohelices by Metal-Nucleobase Recognition, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 56, Pages: 2361-2365, ISSN: 1433-7851

JOURNAL ARTICLE

Macon ALB, Jacquemin M, Page SJ, Li S, Bertazzo S, Stevens MM, Hanna JV, Jones JRet al., 2017, Lithium-silicate sol-gel bioactive glass and the effect of lithium precursor on structure-property relationships, JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY, Vol: 81, Pages: 84-94, ISSN: 0928-0707

JOURNAL ARTICLE

Pacheco-Moreno CM, Schreck M, Scaccabarozzi AD, Bourgun P, Wantz G, Stevens MM, Dautel OJ, Stingelin Net al., 2017, The Importance of Materials Design to Make Ions Flow: Toward Novel Materials Platforms for Bioelectronics Applications, ADVANCED MATERIALS, Vol: 29, ISSN: 0935-9648

JOURNAL ARTICLE

Parmar PA, St-Pierre J-P, Chow LW, Spicer CD, Stoichevska V, Peng YY, Werkmeister JA, Ramshaw JAM, Stevens MMet al., 2017, Enhanced articular cartilage by human mesenchymal stem cells in enzymatically mediated transiently RGDS-functionalized collagen mimetic hydrogels, ACTA BIOMATERIALIA, Vol: 51, Pages: 75-88, ISSN: 1742-7061

JOURNAL ARTICLE

Pelaz B, Alexiou C, Alvarez -Puebla RA, Alves F, Andrews AM, Ashraf S, Balogh LP, Ballerini L, Bestetti A, Brendel C, Bosi S, Carril M, Chan WCW, Chen C, Chen X, Chen X, Cheng Z, Cui D, Du J, Dullin C, Escudero A, Feliu N, Gao M, George M, Gogotsi Y, Grunweller A, Gu Z, Halas NJ, Hampp N, Hartmann RK, Hersam MC, Hunziker P, Jian J, Jiang X, Jungebluth P, Kadhiresan P, Kataoka K, Khademhosseini A, Kopecek J, Kotov NA, Krug HF, Lee DS, Lehr C-M, Leong KW, Liang X-J, Lim ML, Liz-Marzan LM, Ma X, Macchiarini P, Meng H, Mohwald H, Mulvaney P, Nel AE, Nie S, Nordlander P, Okano T, Oliveira J, Park TH, Penner RM, Prato M, Puntes V, Rotello VM, Samarakoon A, Schaak RE, Shen Y, Sjoqvist S, Skirtach AG, Soliman MG, Stevens MM, Sung H-W, Tang BZ, Tietze R, Udugama BN, VanEpps JS, Weil T, Weiss PS, Willner I, Wu Y, Yang L, Yue Z, Zhang Q, Zhang Q, Zhang X-E, Zhao Y, Zhou X, Parak WJet al., 2017, Diverse Applications of Nanomedicine, ACS NANO, Vol: 11, Pages: 2313-2381, ISSN: 1936-0851

JOURNAL ARTICLE

Reznikov N, Phillips C, Cooke M, Garbout A, Ahmed F, Stevens MMet al., 2017, Functional adaptation of the calcaneus in historical foot binding., J Bone Miner Res

The normal structure of human feet is optimized for shock dampening during walking and running. Foot binding was a historical practice in China aimed at restricting the growth of female feet for aesthetic reasons. In a bound foot the shock-dampening function normally facilitated by the foot arches is withdrawn, resulting in the foot functioning as a rigid extension of the lower leg. An interesting question inspiring this study regards the nature of adaptation of the heel bone to this non-physiological function using the parameters of cancellous bone anisotropy and 3D fabric topology using a novel inter-trabecular angle (ITA) analysis. We found that the trabecular microarchitecture only of the normal heel bone, but not of the bound foot, adapts to function by increased anisotropy and preferred orientation of trabeculae. The anisotropic texture in the normal heel bone consistently follows the physiological stress trajectories. Surprisingly however, in the bound foot heel bone the characteristic anisotropy pattern fails to develop, reflecting the lack of a normal biomechanical input. Moreover, the basic topological blueprint of cancellous bone investigated by the ITA method is nearly invariant in both normal and bound foot. These findings suggest that the anisotropic cancellous bone texture is an acquired characteristic that reflects recurrent loading conditions; an inadequate biomechanical input precludes the formation of anisotropic texture. This opens a long sought-after possibility to reconstruct bone function from its form. The conserved topological parameters characterize the generic 3D fabric of cancellous bone, which is to a large extent independent of its adaptation to recurrent loading and perhaps determines the mechanical competence of trabecular bone regardless of its functional adaptation. This article is protected by copyright. All rights reserved.

JOURNAL ARTICLE

Speidel AT, Stuckey DJ, Chow LW, Jackson LH, Noseda M, Paiva MA, Schneider MD, Stevens MMet al., 2017, Multimodal Hydrogel-Based Platform To Deliver and Monitor Cardiac Progenitor/Stem Cell Engraftment, ACS CENTRAL SCIENCE, Vol: 3, Pages: 338-348, ISSN: 2374-7943

JOURNAL ARTICLE

Spicer CD, Booth MA, Mawad D, Armgarth A, Nielsen CB, Stevens MMet al., 2017, Synthesis of Hetero-bifunctional, End-Capped Oligo-EDOT Derivatives., Chem, Vol: 2, Pages: 125-138

Conjugated oligomers of 3,4-ethylenedioxythiophene (EDOT) are attractive materials for tissue engineering applications and as model systems for studying the properties of the widely used polymer poly(3,4-ethylenedioxythiophene). We report here the facile synthesis of a series of keto-acid end-capped oligo-EDOT derivatives (n = 2-7) through a combination of a glyoxylation end-capping strategy and iterative direct arylation chain extension. Importantly, these structures not only represent the longest oligo-EDOTs reported but are also bench stable, in contrast to previous reports on such oligomers. The constructs reported here can undergo subsequent derivatization for integration into higher-order architectures, such as those required for tissue engineering applications. The synthesis of hetero-bifunctional constructs, as well as those containing mixed-monomer units, is also reported, allowing further complexity to be installed in a controlled manner. Finally, we describe the optical and electrochemical properties of these oligomers and demonstrate the importance of the keto-acid in determining their characteristics.

JOURNAL ARTICLE

Wang S-T, Lin Y, Todorova N, Xu Y, Mazo M, Rana S, Leonardo V, Amdursky N, Spicer CD, Alexander BD, Edwards AA, Matthews SJ, Yarovsky I, Stevens MMet al., 2017, Facet-Dependent Interactions of Islet Amyloid Polypeptide with Gold Nanoparticles: Implications for Fibril Formation and Peptide-Induced Lipid Membrane Disruption, CHEMISTRY OF MATERIALS, Vol: 29, Pages: 1550-1560, ISSN: 0897-4756

JOURNAL ARTICLE

Wang ST, Lin Y, Hsu CC, Amdursky N, Spicer CD, Stevens MMet al., 2017, Probing amylin fibrillation at an early stage via a tetracysteine-recognising fluorophore., Talanta, Vol: 173, Pages: 44-50

Amyloid fibrillation is a nucleation-dependent process known be involved in the development of more than 20 progressive and chronic diseases. The detection of amyloid formation at the nucleation stage can greatly advance early diagnoses and treatment of diseases. In this work, we developed a new assay for the early detection of amylin fibrillation using the biarsenical dye 4,5-bis(1,3,2-dithiarsolan-2-yl)fluorescein (FlAsH), which could recognise tetracysteine motifs and transform from non-fluorescent form into strongly fluorescent complexes. Due to the close proximity of two cysteine residues within the hydrophilic domain of amylin, a non-contiguous tetracysteine motif can form upon amylin dimerisation or oligomerisation, which can be recognised by FlAsH and emit strong fluorescence. This enables us to report the nucleation-growth process of amylin without modification of the protein sequence. We showed that the use of this assay not only allowed the tracking of initial nucleation events, but also enabled imaging of amyloid fibrils and investigation of the effects of amyloid inhibitor/modulator toward amylin fibrillation.

JOURNAL ARTICLE

Amdursky N, Wang X, Meredith P, Bradley DDC, Stevens MMet al., 2016, Long-Range Proton Conduction across Free-Standing Serum Albumin Mats, ADVANCED MATERIALS, Vol: 28, Pages: 2692-2698, ISSN: 0935-9648

JOURNAL ARTICLE

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