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

230 results found

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

The ability to simultaneously image multiple biomolecules in biologically relevant three-dimensional (3D) cell culture environments would contribute greatly to the understanding of complex cellular mechanisms and cell-material interactions. Here, we present a computational framework for label-free quantitative volumetric Raman imaging (qVRI). We apply qVRI to a selection of biological systems: human pluripotent stem cells with their cardiac derivatives, monocytes and monocyte-derived macrophages in conventional cell culture systems and mesenchymal stem cells inside biomimetic hydrogels that supplied a 3D cell culture environment. We demonstrate visualization and quantification of fine details in 3D cell shape, cytoplasm, nucleus, lipid bodies and cytoskeletal structures in 3D with unprecedented biomolecular specificity for vibrational microspectroscopy.

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Stevens MM, Horejs CM, St-Pierre JP, Ojala JRM, Steele JAM, Barros da Silva P, Rynne-Vidal A, Maynard SA, Hansel CS, Rodriguez-Fernandez C, Mazo MM, You AYF, Wang AJ, von Erlach T, Tryggvason K, Lopez-Cabrera Met al., Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information, Nature Communications, ISSN: 2041-1723

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Stevens MM, Speidel AT, Stuckey DJ, Chow LW, Jackson LH, Noseda M, Abreu Pavia M, Schneider MDet al., Multi-modal hydrogel-based platform to deliver and monitor cardiac progenitor/stem cell engraftment, ACS Central Science, ISSN: 2374-7951

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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

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Chandrawati R, Chang JY, 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., Adv Mater

Nitric oxide (NO) is able to lower intraocular pressure (IOP); however, its therapeutic effects on outflow physiology are location- and dose-dependent. An NO delivery platform that directly targets the resistance-generating region of the conventional outflow pathway and locally liberates a controlled dose of NO is reported. An increase in outflow facility (decrease in IOP) is demonstrated in a mouse model.

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

Magnesium is a trace element in the human body, known to have important effects on cell differentiation and the mineralisation of calcified tissues. This study aimed to synthesise highly porous Ca-Mg silicate foamed scaffolds from preceramic polymers, with analysis of their biological response. Akermanite (Ak) and wollastonite-diopside (WD) ceramic foams were obtained from the pyrolysis of a liquid silicone mixed with reactive fillers. The porous structure was obtained by controlled water release from selected fillers (magnesium hydroxide and borax) at 350°C. The homogeneous distribution of open pores, with interconnects of modal diameters of 160-180μm was obtained and maintained after firing at 1100°C. Foams, with porosity exceeding 80%, exhibited compressive strength values of 1-2MPa. In vitro studies were conducted by immersion in SBF for 21days, showing suitable dissolution rates, pH and ionic concentrations. Cytotoxicity analysis performed in accordance with ISO10993-5 and ISO10993-12 standards confirmed excellent biocompatibility of both Ak and WD foams. In addition, MC3T3-E1 cells cultured on the Mg-containing scaffolds demonstrated enhanced osteogenic differentiation and the expression of osteogenic markers including Collagen Type I, Osteopontin and Osteocalcin, in comparison to Mg-free counterparts. The results suggest that the addition of magnesium can further enhance the bioactivity and the potential for bone regeneration applications of Ca-silicate materials. STATEMENTS OF SIGNIFICANCE: Here, we show that the incorporation of Mg in Ca-silicates plays a significant role in the enhancement of the osteogenic differentiation and matrix formation of MC3T3-E1 cells, cultured on polymer-derived highly porous scaffolds. Reduced degradation rates and improved mechanical properties are also observed, compared to Mg-free counterparts, suggesting the great potential of Ca-Mg silicates as bone tissue engineering materials. Excellent biocompatibility of the

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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

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Lin Y, Pashuck ET, Thomas MR, Amdursky N, Wang ST, Chow LW, Stevens MMet al., 2017, Plasmonic Chirality Imprinting on Nucleobase-Displaying Supramolecular Nanohelices by Metal-Nucleobase Recognition., Angew Chem Int Ed Engl, Vol: 56, Pages: 2361-2365

Supramolecular self-assembly is an important process that enables the conception of complex structures mimicking biological motifs. Herein, we constructed helical fibrils through chiral self-assembly of nucleobase-peptide conjugates (NPCs), where achiral nucleobases are helically displayed on the surface of fibrils, comparable to polymerized nucleic acids. Selective binding between DNA and the NPC fibrils was observed with fluorescence polarization. Taking advantage of metal-nucleobase recognition, we highlight the possibility of deposition/assembly of plasmonic nanoparticles onto the fibrillar constructs. In this approach, the supramolecular chirality of NPCs can be adaptively imparted to metallic nanoparticles, covering them to generate structures with plasmonic chirality that exhibit significantly improved colloidal stability. The self-assembly of rationally designed NPCs into nanohelices is a promising way to engineer complex, optically diverse nucleobase-derived nanomaterials.

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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

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

Recapitulation of the articular cartilage microenvironment for regenerative medicine applications faces significant challenges due to the complex and dynamic biochemical and biomechanical nature of native tissue. Towards the goal of biomaterial designs that enable the temporal presentation of bioactive sequences, recombinant bacterial collagens such as Streptococcal collagen-like 2 (Scl2) proteins can be employed to incorporate multiple specific bioactive and biodegradable peptide motifs into a single construct. Here, we first modified the backbone of Scl2 with glycosaminoglycan-binding peptides and cross-linked the modified Scl2 into hydrogels via matrix metalloproteinase 7 (MMP7)-cleavable or non-cleavable scrambled peptides. The cross-linkers were further functionalized with a tethered RGDS peptide creating a system whereby the release from an MMP7-cleavable hydrogel could be compared to a system where release is not possible. The release of the RGDS peptide from the degradable hydrogels led to significantly enhanced expression of collagen type II (3.9-fold increase), aggrecan (7.6-fold increase), and SOX9 (5.2-fold increase) by human mesenchymal stem cells (hMSCs) undergoing chondrogenesis, as well as greater extracellular matrix accumulation compared to non-degradable hydrogels (collagen type II; 3.2-fold increase, aggrecan; 4-fold increase, SOX9; 2.8-fold increase). Hydrogels containing a low concentration of the RGDS peptide displayed significantly decreased collagen type I and X gene expression profiles, suggesting a major advantage over either hydrogels functionalized with a higher RGDS peptide concentration, or non-degradable hydrogels, in promoting an articular cartilage phenotype. These highly versatile Scl2 hydrogels can be further manipulated to improve specific elements of the chondrogenic response by hMSCs, through the introduction of additional bioactive and/or biodegradable motifs. As such, these hydrogels have the possibility to be used for other

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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.

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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

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Bell RV, Parkins CC, Young RA, Preuss CM, Stevens MM, Bon SAFet al., 2016, Assembly of emulsion droplets into fibers by microfluidic wet spinning, JOURNAL OF MATERIALS CHEMISTRY A, Vol: 4, Pages: 813-818, ISSN: 2050-7488

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Bergholt MS, St-Pierre J-P, Offeddu GS, Parmar PA, Albro MB, Puetzer JL, Oyen ML, Stevens MMet al., 2016, Raman Spectroscopy Reveals New Insights into the Zonal Organization of Native and Tissue-Engineered Articular Cartilage, ACS CENTRAL SCIENCE, Vol: 2, Pages: 885-895, ISSN: 2374-7943

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Blaeser A, Campos DFD, Puster U, Richtering W, Stevens MM, Fischer Het al., 2016, Controlling Shear Stress in 3D Bioprinting is a Key Factor to Balance Printing Resolution and Stem Cell Integrity, ADVANCED HEALTHCARE MATERIALS, Vol: 5, Pages: 326-333, ISSN: 2192-2640

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Campagnolo P, Gormley AJ, Chow LW, Guex AG, Parmar PA, Puetzer JL, Steele JAM, Breant A, Madeddu P, Stevens MMet al., 2016, Pericyte Seeded Dual Peptide Scaffold with Improved Endothelialization for Vascular Graft Tissue Engineering, ADVANCED HEALTHCARE MATERIALS, Vol: 5, Pages: 3046-3055, ISSN: 2192-2640

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Chapman R, Gormley AJ, Stenzel MH, Stevens MMet al., 2016, Combinatorial Low-Volume Synthesis of Well-Defined Polymers by Enzyme Degassing, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 55, Pages: 4500-4503, ISSN: 1433-7851

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Chung JJ, Li S, Stevens MM, Georgiou TK, Jones JRet al., 2016, Tailoring Mechanical Properties of Sol-Gel Hybrids for Bone Regeneration through Polymer Structure, CHEMISTRY OF MATERIALS, Vol: 28, Pages: 6127-6135, ISSN: 0897-4756

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Crowder SW, Leonardo V, Whittaker T, Papathanasiou P, Stevens MMet al., 2016, Material Cues as Potent Regulators of Epigenetics and Stem Cell Function, CELL STEM CELL, Vol: 18, Pages: 39-52, ISSN: 1934-5909

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Fiocco L, Li S, Bernardo E, Stevens MM, Jones JRet al., 2016, Highly porous polymer-derived wollastonite-hydroxycarbonate apatite ceramics for bone regeneration, BIOMEDICAL MATERIALS, Vol: 11, ISSN: 1748-6041

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Flamant Q, Caravaca C, Meille S, Gremillard L, Chevalier J, Biotteau-Deheuvels K, Kuntz M, Chandrawati R, Herrmann IK, Spicer CD, Stevens MM, Anglada Met al., 2016, Selective etching of injection molded zirconia-toughened alumina: Towards osseointegrated and antibacterial ceramic implants, ACTA BIOMATERIALIA, Vol: 46, Pages: 308-322, ISSN: 1742-7061

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Gliddon HD, Howes PD, Kaforou M, Levin M, Stevens MMet al., 2016, A nucleic acid strand displacement system for the multiplexed detection of tuberculosis-specific mRNA using quantum dots, NANOSCALE, Vol: 8, Pages: 10087-10095, ISSN: 2040-3364

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He M, Callanan A, Lagaras K, Steele JA, Stevens MMet al., 2016, Optimization of SDS exposure on preservation of ECM characteristics in whole organ decellularization of rat kidneys., J Biomed Mater Res B Appl Biomater

Renal transplantation is well established as the optimal form of renal replacement therapy but is restricted by the limited pool of organs available for transplantation. The whole organ decellularisation approach is leading the way for a regenerative medicine solution towards bioengineered organ replacements. However, systematic preoptimization of both decellularization and recellularization parameters is essential prior to any potential clinical application and should be the next stage in the evolution of whole organ decellularization as a potential strategy for bioengineered organ replacements. Here we have systematically assessed two fundamental parameters (concentration and duration of perfusion) with regards to the effects of differing exposure to the most commonly used single decellularizing agent (sodium dodecyl sulphate/SDS) in the perfusion decellularization process for whole rat kidney ECM bioscaffolds, with findings showing improved preservation of both structural and functional components of the whole kidney ECM bioscaffold. Whole kidney bioscaffolds based on our enhanced protocol were successfully recellularized with rat primary renal cells and mesenchymal stromal cells. These findings should be widely applicable to decellularized whole organ bioscaffolds and their optimization in the development of regenerated organ replacements for transplantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

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Hedegaard MAB, Bergholt MS, Stevens MM, 2016, Quantitative multi-image analysis for biomedical Raman spectroscopic imaging, JOURNAL OF BIOPHOTONICS, Vol: 9, Pages: 542-550, ISSN: 1864-063X

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Liu NJ, Chapman R, Lin Y, Bentham A, Tyreman M, Philips N, Khan SA, Stevens MMet al., 2016, Phospholipase A2 as a point of care alternative to serum amylase and pancreatic lipase, NANOSCALE, Vol: 8, Pages: 11834-11839, ISSN: 2040-3364

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Liu NJ, Chapman R, Lin Y, Mmesi J, Bentham A, Tyreman M, Abraham S, Stevens MMet al., 2016, Point of care testing of phospholipase A2 group IIA for serological diagnosis of rheumatoid arthritis, NANOSCALE, Vol: 8, Pages: 4482-4485, ISSN: 2040-3364

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Macon ALB, Li S, Chung JJ, Nommeots-Nomm A, Solanki AK, Stevens MM, Jones JRet al., 2016, Ductile silica/methacrylate hybrids for bone regeneration, JOURNAL OF MATERIALS CHEMISTRY B, Vol: 4, Pages: 6032-6042, ISSN: 2050-750X

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Mawad D, Artzy-Schnirman A, Tonkin J, Ramos J, Inal S, Mahat MM, Darwish N, Zwi-Dantsis L, Malliaras GG, Gooding JJ, Lauto A, Stevens MMet al., 2016, Electroconductive Hydrogel Based on Functional Poly(Ethylenedioxy Thiophene), CHEMISTRY OF MATERIALS, Vol: 28, Pages: 6080-6088, ISSN: 0897-4756

JOURNAL ARTICLE

Mawad D, Mansfield C, Lauto A, Perbellini F, Nelson GW, Tonkin J, Bello SO, Carrad DJ, Micolich AP, Mahat MM, Furman J, Payne D, Lyon AR, Gooding JJ, Harding SE, Terracciano CM, Stevens MMet al., 2016, A conducting polymer with enhanced electronic stability applied in cardiac models., Sci Adv, Vol: 2

Electrically active constructs can have a beneficial effect on electroresponsive tissues, such as the brain, heart, and nervous system. Conducting polymers (CPs) are being considered as components of these constructs because of their intrinsic electroactive and flexible nature. However, their clinical application has been largely hampered by their short operational time due to a decrease in their electronic properties. We show that, by immobilizing the dopant in the conductive scaffold, we can prevent its electric deterioration. We grew polyaniline (PANI) doped with phytic acid on the surface of a chitosan film. The strong chelation between phytic acid and chitosan led to a conductive patch with retained electroactivity, low surface resistivity (35.85 ± 9.40 kilohms per square), and oxidized form after 2 weeks of incubation in physiological medium. Ex vivo experiments revealed that the conductive nature of the patch has an immediate effect on the electrophysiology of the heart. Preliminary in vivo experiments showed that the conductive patch does not induce proarrhythmogenic activities in the heart. Our findings set the foundation for the design of electronically stable CP-based scaffolds. This provides a robust conductive system that could be used at the interface with electroresponsive tissue to better understand the interaction and effect of these materials on the electrophysiology of these tissues.

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Maçon ALB, Jacquemin M, Page SJ, Li S, Bertazzo S, Stevens MM, Hanna JV, Jones JRet al., 2016, Lithium-silicate sol–gel bioactive glass and the effect of lithium precursor on structure–property relationships, Journal of Sol-Gel Science and Technology, ISSN: 0928-0707

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