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

350 results found

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

Todorova N, Chiappini C, Mager M, Simona B, Patel II, Stevens MM, Yarovsky Iet al., 2014, Surface presentation of functional peptides in solution determines cell internalization efficiency of TAT conjugated nanoparticles, Nano Letters, Vol: 14, Pages: 5229-5237, ISSN: 1530-6984

Functionalizing nanoparticles with cell-penetrating peptides is a popular choice for cellular delivery. We investigated the effects of TAT peptide concentration and arrangement in solution on functionalized nanoparticles’ efficacy for membrane permeation. We found that cell internalization correlates with the positive charge distribution achieved prior to nanoparticle encountering interactions with membrane. We identified a combination of solution based properties required to maximize the internalization efficacy of TAT-functionalized nanoparticles.

Journal article

Cecchin D, de la Rica R, Bain RES, Finnis MW, Stevens MM, Battaglia Get al., 2014, Plasmonic ELISA for the detection of gp120 at ultralow concentrations with the naked eye, NANOSCALE, Vol: 6, Pages: 9559-9562, ISSN: 2040-3364

Journal article

Andresen H, Mager M, Griessner M, Charchar P, Todorova N, Bell N, Theocharidis G, Bertazzo S, Yarovsky I, Stevens MMet al., 2014, Single-step homogeneous immunoassays utilizing epitope-tagged gold nanoparticles: on the mechanism, feasibility, and limitations, Chemistry of Materials, Vol: 26, Pages: 4696-4704, ISSN: 0897-4756

A single-step gold nanoparticle (AuNP)-based immunoassay is demonstrated in which the nanoparticle surface is tagged with short viral peptide epitopes. Antiviral antibodies with monoclonal specificity trigger nanoparticle aggregation yielding a colorimetric response that enables detection of antibodies in the low-nanomolar range within a few minutes. In silico insights into the interactions at the epitope–gold interface demonstrate that the conformational landscape exhibited by the epitopes is strongly influenced by the amino acid sequence and location of particular residues within the peptides. The conformation, orientation, and linker chemistry of the peptides affect the immune complex formation in nonintuitive ways that are, nevertheless, explained by a unique sterically kinetically driven aggregation mechanism. The rapid and specific performance of the AuNP immunoassay may have generic potential in point of care diagnostics and other laboratory routines.

Journal article

Hedegaard MAB, Cloyd KL, Horejs C-M, Stevens MMet al., 2014, Model based variable selection as a tool to highlight biological differences in Raman spectra of cells, Analyst, Vol: 139, Pages: 4629-4633, ISSN: 0003-2654

Journal article

Nair R, Santos L, Awasthi S, von Erlach T, Chow LW, Bertazzo S, Stevens MMet al., 2014, Extracellular vesicles derived from preosteoblasts influence embryonic stem cell differentiation, Stem Cells and Development, Vol: 23, Pages: 1625-1635, ISSN: 1557-8534

Journal article

Poologasundarampillai G, Yu B, Tsigkou O, Wang D, Romer F, Bhakhri V, Giuliani F, Stevens MM, McPhail DS, Smith ME, Hanna JV, Jones JRet al., 2014, Poly(gamma-glutamic acid)/Silica Hybrids with Calcium Incorporated in the Silica Network by Use of a Calcium Alkoxide Precursor, Chemistry-A European Journal, Vol: 20, Pages: 8149-8160, ISSN: 1521-3765

Current materials used for bone regeneration are usually bioactive ceramics or glasses. Although they bond to bone, they are brittle. There is a need for new materials that can combine bioactivity with toughness and controlled biodegradation. Sol-gel hybrids have the potential to do this through their nanoscale interpenetrating networks (IPN) of inorganic and organic components. Poly(γ-glutamic acid) (γ-PGA) was introduced into the sol-gel process to produce a hybrid of γ-PGA and bioactive silica. Calcium is an important element for bone regeneration but calcium sources that are used traditionally in the sol-gel process, such as Ca salts, do not allow Ca incorporation into the silicate network during low-temperature processing. The hypothesis for this study was that using calcium methoxyethoxide (CME) as the Ca source would allow Ca incorporation into the silicate component of the hybrid at room temperature. The produced hybrids would have improved mechanical properties and controlled degradation compared with hybrids of calcium chloride (CaCl2), in which the Ca is not incorporated into the silicate network. Class II hybrids, with covalent bonds between the inorganic and organic species, were synthesised by using organosilane. Calcium incorporation in both the organic and inorganic IPNs of the hybrid was improved when CME was used. This was clearly observed by using FTIR and solid-state NMR spectroscopy, which showed ionic cross-linking of γ-PGA by Ca and a lower degree of condensation of the Si species compared with the hybrids made with CaCl2 as the Ca source. The ionic cross-linking of γ-PGA by Ca resulted in excellent compressive strength and reduced elastic modulus as measured by compressive testing and nanoindentation, respectively. All hybrids showed bioactivity as hydroxyapatite (HA) was formed after immersion in simulated body fluid (SBF).

Journal article

Lin Y, Chapman R, Stevens MM, 2014, Label-free multimodal protease detection based on protein/perylene dye coassembly and enzyme-triggered disassembly, Analytical Chemistry, Vol: 86, Pages: 6410-6417, ISSN: 1086-4377

Journal article

de la Rica R, Mendoza E, Chow LW, Cloyd KL, Bertazzo S, Watkins HC, Steele JAM, Stevens MMet al., 2014, Self-assembly of collagen building blocks guided by electric fields, Small, Vol: 10, Pages: 3876-3879, ISSN: 1613-6810

Show me the way: protein building blocks are programmed to assemble hierarchically and yield a defined fiber morphology of micrometric length and precise nanometric diameter. The key step of this method is to align the building blocks with an AC field prior to assembly. The resulting protein nanofibers are straightforwardly integrated with the circuitry for potential applications in bionanotechnology.

Journal article

Smith EL, Kanczler JM, Gothard D, Roberts CA, White LJ, Qutachi O, Rashidi H, Rojo L, Stevens MM, Shakesheff KM, Oreffo ROet al., 2014, Dual growth factor-releasing hydrogels for enhancement of skeletal tissue repair within an ex vivo chick femur defect model, JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Vol: 8, Pages: 361-361, ISSN: 1932-6254

Journal article

de la Rica R, Bat E, Herpoldt KL, Xie H-N, Bertazzo S, Maynard HD, Stevens MMet al., 2014, Nanoparticle growth via concentration gradients generated by enzyme nanopatterns, Advanced Functional Materials, Vol: 24, Pages: 3692-3698, ISSN: 1616-3028

Journal article

Poologasundarampillai G, Wang D, Li S, Nakamura J, Bradley R, Lee PD, Stevens MM, McPhail DS, Kasuga T, Jones JRet al., 2014, Cotton-wool-like bioactive glasses for bone regeneration, Acta Biomaterialia, Vol: 10, Pages: 3733-3746, ISSN: 1742-7061

Inorganic sol–gel solutions were electrospun to produce the first bioactive three-dimensional (3-D) scaffolds for bone tissue regeneration with a structure like cotton-wool (or cotton candy). This flexible 3-D fibrous structure is ideal for packing into complex defects. It also has large inter-fiber spaces to promote vascularization, penetration of cells and transport of nutrients throughout the scaffold. The 3-D fibrous structure was obtained by electrospinning, where the applied electric field and the instabilities exert tremendous force on the spinning jet, which is required to be viscoelastic to prevent jet break up. Previously, polymer binding agents were used with inorganic solutions to produce electrospun composite two-dimensional fibermats, requiring calcination to remove the polymer. This study presents novel reaction and processing conditions for producing a viscoelastic inorganic sol–gel solution that results in fibers by the entanglement of the intermolecularly overlapped nanosilica species in the solution, eliminating the need for a binder. Three-dimensional cotton-wool-like structures were only produced when solutions containing calcium nitrate were used, suggesting that the charge of the Ca2+ ions had a significant effect. The resulting bioactive silica fibers had a narrow diameter range of 0.5–2 μm and were nanoporous. A hydroxycarbonate apatite layer was formed on the fibers within the first 12 h of soaking in simulated body fluid. MC3T3-E1 preosteoblast cells cultured on the fibers showed no adverse cytotoxic effect and they were observed to attach to and spread in the material.

Journal article

Bertazzo S, Steele JAM, Chester AH, Yacoub MH, Stevens MMet al., 2014, Cardiovascular calcification violet pearl, The Lancet, Vol: 384, Pages: 1294-1294, ISSN: 0140-6736

Journal article

Steele JAM, McCullen SD, Callanan A, Autefage H, Accardi MA, Dini D, Stevens MMet al., 2014, Combinatorial scaffold morphologies for zonal articular cartilage engineering, ACTA BIOMATERIALIA, Vol: 10, Pages: 2065-2075, ISSN: 1742-7061

Journal article

Horejs C-M, Serio A, Purvis A, Gormley AJ, Bertazzo S, Poliniewicz A, Wang AJ, DiMaggio P, Hohenester E, Stevens MMet al., 2014, Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells, Proceedings of the National Academy of Sciences, Vol: 111, Pages: 5908-5913, ISSN: 1091-6490

The dynamic interplay between the extracellular matrix and embryonic stem cells (ESCs) constitutes one of the key steps in understanding stem cell differentiation in vitro. Here we report a biologically-active laminin-111 fragment generated by matrix metalloproteinase 2 (MMP2) processing, which is highly up-regulated during differentiation. We show that the β1-chain–derived fragment interacts via α3β1-integrins, thereby triggering the down-regulation of MMP2 in mouse and human ESCs. Additionally, the expression of MMP9 and E-cadherin is up-regulated in mouse ESCs—key players in the epithelial-to-mesenchymal transition. We also demonstrate that the fragment acts through the α3β1-integrin/extracellular matrix metalloproteinase inducer complex. This study reveals a previously unidentified role of laminin-111 in early stem cell differentiation that goes far beyond basement membrane assembly and a mechanism by which an MMP2-cleaved laminin fragment regulates the expression of E-cadherin, MMP2, and MMP9.

Journal article

Basey-Fisher TH, Guerra N, Triulzi C, Gregory A, Hanham SM, Stevens MM, Maier SA, Klein Net al., 2014, Microwaving Blood as a Non-Destructive Technique for Haemoglobin Measurements on Microlitre Samples, ADVANCED HEALTHCARE MATERIALS, Vol: 3, Pages: 536-542, ISSN: 2192-2640

Journal article

Basey-Fisher TH, Guerra N, Triulzi C, Gregory A, Hanham SM, Stevens MM, Maier SA, Klein Net al., 2014, Blood measurements: microwaving blood as a non-destructive technique for haemoglobin measurements on microlitre samples (adv. Healthcare mater. 4/2014)., Adv Healthc Mater, Vol: 3

The electric field component of the microwaves emanating from the dielectric resonator is able to penetrate the microfluidic channel, serum, and individual blood cells. Subsequently, it interacts with every hemoglobin molecule present within each red blood cell. On page 536 , Toby H. Basey-Fisher and team conclude that the dielectric contrast between water and hemoglobin means that a change in the hemoglobin concentration leads to a change in the microwave response.

Journal article

Newman SD, Lotfibakhshaiesh N, O'Donnell M, Walboomers XF, Horwood N, Jansen JA, Amis AA, Cobb JP, Stevens MMet al., 2014, Enhanced Osseous Implant Fixation with Strontium-Substituted Bioactive Glass Coating, TISSUE ENGINEERING PART A, Vol: 20, Pages: 1850-1857, ISSN: 1937-3341

The use of endosseous implants is firmly established in skeletal reconstructive surgery, with rapid and permanent fixation of prostheses being a highly desirable feature. Implant coatings composed of hydroxyapatite (HA) have become the standard and have been used with some success in prolonging the time to revision surgery, but aseptic loosening remains a significant issue. The development of a new generation of more biologically active coatings is a promising approach for tackling this problem. Bioactive glasses are an ideal candidate material due to the osteostimulative properties of their dissolution products. However, to date, they have not been formulated with stability to devitrification or thermal expansion coefficients (TECs) that are suitable for stable coating onto metal implants while still retaining their bioactive properties. Here, we present a strontium-substituted bioactive glass (SrBG) implant coating which has been designed to encourage peri-implant bone formation and with a TEC similar to that of HA. The coating can be successfully applied to roughened Ti6Al4V and after implantation into the distal femur and proximal tibia of twenty-seven New Zealand White rabbits for 6, 12, or 24 weeks, it produced no adverse tissue reaction. The glass dissolved over a 6 week period, stimulating enhanced peri-implant bone formation compared with matched HA coated implants in the contralateral limb. Furthermore, superior mechanical fixation was evident in the SrBG group after 24 weeks of implantation. We propose that this coating has the potential to enhance implant fixation in a variety of orthopedic reconstructive surgery applications.

Journal article

Chandrawati R, Stevens MM, 2014, Controlled assembly of peptide-functionalized gold nanoparticles for label-free detection of blood coagulation Factor XIII activity, Chemical Communications, Vol: 50, Pages: 5431-5434, ISSN: 1364-548X

Journal article

Chow LW, Armgarth A, St-Pierre J-P, Bertazzo S, Gentilini C, Aurisicchio C, McCullen SD, Steele JAM, Stevens MMet al., 2014, Peptide-Directed Spatial Organization of Biomolecules in Dynamic Gradient Scaffolds, Advanced Healthcare Materials, Vol: 3, Pages: 1381-1386, ISSN: 2192-2640

Journal article

da Silva MA, Bode F, Drake AF, Goldoni S, Stevens MM, Dreiss CAet al., 2014, Enzymatically cross-linked gelatin/chitosan hydrogels: tuning gel properties and cellular response, Macromolecular Bioscience, Vol: 14, Pages: 817-830, ISSN: 1616-5187

This work investigates the effect of combining physical and chemical gelation processes in a biopolymer blend: chitosan and tilapia fish gelatin. Chemical (C) gels are obtained by cross-linking with the microbial enzyme transglutaminase at 37 °C. Hybrid physical-co-chemical (PC) gels are cross-linked at 21 °C, below gelatin gelation temperature. These protocols provide two microenvironments for the gelation process: in C gels, both gelatin and chitosan are present as single strands; in PC gels, cross-linking proceeds within a transient physical gel of gelatin, filled by chitosan strands. The chitosan/gelatin chemical networks generated in PC gels show a consistently higher shear modulus than pure C gels; they are also less turbid than their C gels counterparts, suggesting a more homogeneous network. Finally, chitosan enhances the gels' shear modulus in all gels. Proliferation assays show that MC3T3 cells proliferate in these mixed, hybrid gels and better so on PC gels than in C mixed gels

Journal article

Amin HD, Brady MA, St-Pierre J-P, Stevens MM, Overby DR, Ethier CRet al., 2014, Stimulation of chondrogenic differentiation of adult human bone marrow-derived stromal cells by a moderate-strength static magnetic field, Tissue Engineering: Parts A, B, and C, Vol: 20, Pages: 1612-1620, ISSN: 1937-3368

Tissue-engineering strategies for the treatment of osteoarthritis would benefit from the ability to induce chondrogenesis in precursor cells. One such cell source is bone marrow-derived stromal cells (BMSCs). Here, we examined the effects of moderate-strength static magnetic fields (SMFs) on chondrogenic differentiation in human BMSCs in vitro. Cells were cultured in pellet form and exposed to several strengths of SMFs for various durations. mRNA transcript levels of the early chondrogenic transcription factor SOX9 and the late marker genes ACAN and COL2A1 were determined by reverse transcription–polymerase chain reaction, and production of the cartilage-specific macromolecules sGAG, collage type 2 (Col2), and proteoglycans was determined both biochemically and histologically. The role of the transforming growth factor (TGF)-β signaling pathway was also examined. Results showed that a 0.4 T magnetic field applied for 14 days elicited a strong chondrogenic differentiation response in cultured BMSCs, so long as TGF-β3 was also present, that is, a synergistic response of a SMF and TGF-β3 on BMSC chondrogenic differentiation was observed. Further, SMF alone caused TGF-β secretion in culture, and the effects of SMF could be abrogated by the TGF-β receptor blocker SB-431542. These data show that moderate-strength magnetic fields can induce chondrogenesis in BMSCs through a TGF-β-dependent pathway. This finding has potentially important applications in cartilage tissue-engineering strategies.

Journal article

Harrison RH, St-Pierre J-P, Stevens MM, 2014, Tissue Engineering and Regenerative Medicine: A Year in Review, Tissue Engineering Part B-Reviews, Vol: 20, Pages: 1-16, ISSN: 1937-3376

Journal article

Tsigkou O, Labbaf S, Stevens MM, Porter AE, Jones JRet al., 2014, Monodispersed Bioactive Glass Submicron Particles and Their Effect on Bone Marrow and Adipose Tissue-Derived Stem Cells, ADVANCED HEALTHCARE MATERIALS, Vol: 3, Pages: 115-125, ISSN: 2192-2640

Journal article

May JR, Gentilini C, Clarke DE, Odarchenko YI, Anokhin DV, Ivanov DA, Feldman K, Smith P, Stevens MMet al., 2014, Tailoring of mechanical properties of derivatized natural polyamino acids through esterification and tensile deformation, RSC ADVANCES, Vol: 4, Pages: 2096-2102, ISSN: 2046-2069

Journal article

Chan WCW, Gogotsi Y, Hafner JH, Hammond PT, Hersam MC, Javey A, Kagan CR, Khademhosseini A, Kotov NA, 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., 2013, Exciting Times for Nano, ACS Nano, Vol: 7, Pages: 10437-10439, ISSN: 1936-0851

Journal article

Howes PD, Rana S, Stevens MM, 2013, Plasmonic nanomaterials for biodiagnostics, Chemical Society Reviews, Vol: 43, Pages: 3835-3853, ISSN: 0306-0012

The application of nanomaterials to detect disease biomarkers is giving rise to ultrasensitive assays, with scientists exploiting the many advantageous physical and chemical properties of nanomaterials. The fundamental basis of such work is to link unique phenomena that arise at the nanoscale to the presence of a specific analyte biomolecule, and to modulate the intensity of such phenomena in a ratiometric fashion, in direct proportion with analyte concentration. Precise engineering of nanomaterial surfaces is of utmost importance here, as the interface between the material and the biological environment is where the key interactions occur. In this tutorial review, we discuss the use of plasmonic nanomaterials in the development of biodiagnostic tools for the detection of a large variety of biomolecular analytes, and how their plasmonic properties give rise to tunable optical characteristics and surface enhanced Raman signals. We put particular focus on studies that have explored the efficacy of the systems using physiological samples in an effort to highlight the clinical potential of such assays.

Journal article

Poh PSP, Hutmacher DW, Stevens MM, Woodruff MAet al., 2013, Fabrication and in vitro characterization of bioactive glass composite scaffolds for bone regeneration, BIOFABRICATION, Vol: 5, ISSN: 1758-5082

Journal article

LaPointe VLS, Fernandes AT, Bell NC, Stellacci F, Stevens MMet al., 2013, Nanoscale Topography and Chemistry Affect Embryonic Stem Cell Self-Renewal and Early Differentiation, ADVANCED HEALTHCARE MATERIALS, Vol: 2, Pages: 1644-1650, ISSN: 2192-2640

Journal article

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