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

303 results found

Albro MB, Bergholt MS, St-Pierre JP, Vinals Guitart A, Zlotnick HM, Evita EG, Stevens MMet al., 2018, Raman spectroscopic imaging for quantification of depth-dependent and local heterogeneities in native and engineered cartilage., NPJ Regen Med, Vol: 3

Articular cartilage possesses a remarkable, mechanically-robust extracellular matrix (ECM) that is organized and distributed throughout the tissue to resist physiologic strains and provide low friction during articulation. The ability to characterize the make-up and distribution of the cartilage ECM is critical to both understand the process by which articular cartilage undergoes disease-related degeneration and to develop novel tissue repair strategies to restore tissue functionality. However, the ability to quantitatively measure the spatial distribution of cartilage ECM constituents throughout the tissue has remained a major challenge. In this experimental investigation, we assessed the analytical ability of Raman micro-spectroscopic imaging to semi-quantitatively measure the distribution of the major ECM constituents in cartilage tissues. Raman spectroscopic images were acquired of two distinct cartilage tissue types that possess large spatial ECM gradients throughout their depth: native articular cartilage explants and large engineered cartilage tissue constructs. Spectral acquisitions were processed via multivariate curve resolution to decompose the "fingerprint" range spectra (800-1800 cm-1) to the component spectra of GAG, collagen, and water, giving rise to the depth dependent concentration profile of each constituent throughout the tissues. These Raman spectroscopic acquired-profiles exhibited strong agreement with profiles independently acquired via direct biochemical assaying of spatial tissue sections. Further, we harness this spectroscopic technique to evaluate local heterogeneities through the depth of cartilage. This work represents a powerful analytical validation of the accuracy of Raman spectroscopic imaging measurements of the spatial distribution of biochemical components in a biological tissue and shows that it can be used as a valuable tool for quantitatively measuring the distribution and organization of ECM constituents in n

JOURNAL ARTICLE

Bergholt MS, Serio A, McKenzie JS, Boyd A, Soares RF, Tillner J, Chiappini C, Wu V, Dannhorn A, Takats Z, Williams A, Stevens MMet al., 2018, Correlated Heterospectral Lipidomics for Biomolecular Profiling of Remyelination in Multiple Sclerosis, ACS CENTRAL SCIENCE, Vol: 4, Pages: 39-51, ISSN: 2374-7943

JOURNAL ARTICLE

Brangel P, Sobarzo A, Parolo C, Miller BS, Howes PD, Gelkop S, Lutwarna JJ, Dye JM, McKendry RA, Lobel L, Stevens MMet al., 2018, A Serological Point-of-Care Test for the Detection of IgG Antibodies against Ebola Virus in Human Survivors, ACS NANO, Vol: 12, Pages: 63-73, ISSN: 1936-0851

JOURNAL ARTICLE

Fuhrmann G, Chandrawati R, Parmar PA, Keane TJ, Maynard SA, Bertazzo S, Stevens MMet al., 2018, Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy., Adv Mater

Extracellular vesicles (EVs) have recently gained significant attention as important mediators of intercellular communication, potential drug carriers, and disease biomarkers. These natural cell-derived nanoparticles are postulated to be biocompatible, stable under physiological conditions, and to show reduced immunogenicity as compared to other synthetic nanoparticles. Although initial clinical trials are ongoing, the use of EVs for therapeutic applications may be limited due to undesired off-target activity and potential "dilution effects" upon systemic administration which may affect their ability to reach their target tissues. To fully exploit their therapeutic potential, EVs are embedded into implantable biomaterials designed to achieve local delivery of therapeutics taking advantage of enzyme prodrug therapy (EPT). In this first application of EVs for an EPT approach, EVs are used as smart carriers for stabilizing enzymes in a hydrogel for local controlled conversion of benign prodrugs to active antiinflammatory compounds. It is shown that the natural EVs' antiinflammatory potential is comparable or superior to synthetic carriers, in particular upon repeated long-term incubations and in different macrophage models of inflammation. Moreover, density-dependent color scanning electron microscopy imaging of EVs in a hydrogel is presented herein, an impactful tool for further understanding EVs in biological settings.

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Hsu C-C, Serio A, Arndursky N, Besnard C, Stevens MMet al., 2018, Fabrication of Hemin-Doped Serum Albumin-Based Fibrous Scaffolds for Neural Tissue Engineering Applications, ACS APPLIED MATERIALS & INTERFACES, Vol: 10, Pages: 5305-5317, ISSN: 1944-8244

JOURNAL ARTICLE

Jumeaux C, Wahlsten O, Block S, Kim E, Chandrawati R, Howes PD, Hook F, Stevens MMet al., 2018, MicroRNA Detection by DNA-Mediated Liposome Fusion, CHEMBIOCHEM, Vol: 19, Pages: 434-438, ISSN: 1439-4227

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Keane TJ, Horejs C-M, Stevens MM, 2018, Scarring vs. functional healing: Matrix-based strategies to regulate tissue repair., Adv Drug Deliv Rev

All vertebrates possess mechanisms to restore damaged tissues with outcomes ranging from regeneration to scarring. Unfortunately, the mammalian response to tissue injury most often culminates in scar formation. Accounting for nearly 45% of deaths in the developed world, fibrosis is a process that stands diametrically opposed to functional tissue regeneration. Strategies to improve wound healing outcomes therefore require methods to limit fibrosis. Wound healing is guided by precise spatiotemporal deposition and remodelling of the extracellular matrix (ECM). The ECM, comprising the non-cellular component of tissues, is a signalling depot that is differentially regulated in scarring and regenerative healing. This Review focuses on the importance of the native matrix components during mammalian wound healing alongside a comparison to scar-free healing and then presents an overview of matrix-based strategies that attempt to exploit the role of the ECM to improve wound healing outcomes.

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Littmann E, Autefage H, Solanki AK, Kallepitis C, Jones JR, Alini M, Peroglio M, Stevens MMet al., 2018, Cobalt-containing bioactive glasses reduce human mesenchymal stem cell chondrogenic differentiation despite HIF-1 alpha stabilisation, JOURNAL OF THE EUROPEAN CERAMIC SOCIETY, Vol: 38, Pages: 877-886, ISSN: 0955-2219

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Loynachan CN, Thomas MR, Gray ER, Richards DA, Kim J, Miller BS, Brookes JC, Agarwal S, Chudasama V, McKendry RA, Stevens MMet al., 2018, Platinum Nanocatalyst Amplification: Redefining the Gold Standard for Lateral Flow Immunoassays with Ultrabroad Dynamic Range, ACS NANO, Vol: 12, Pages: 279-288, ISSN: 1936-0851

JOURNAL ARTICLE

Milner PE, Parkes M, Puetzer JL, Chapman R, Stevens MM, Cann P, Jeffers JRTet al., 2018, A low friction, biphasic and boundary lubricating hydrogel for cartilage replacement, ACTA BIOMATERIALIA, Vol: 65, Pages: 102-111, ISSN: 1742-7061

JOURNAL ARTICLE

Rizzo R, Alvaro M, Danz N, Napione L, Descrovi E, Schmieder S, Sinibaldi A, Rana S, Chandrawati R, Munzert P, Schubert T, Maillart E, Anopchenko A, Rivolo P, Mascioletti A, Förster E, Sonntag F, Stevens MM, Bussolino F, Michelotti Fet al., 2018, Bloch surface wave enhanced biosensor for the direct detection of angiopoietin-2 tumor biomarker in human plasma, Biomedical Optics Express, Vol: 9, Pages: 529-542, ISSN: 2156-7085

Quantitative detection of angiogenic biomarkers provides a powerful tool to diagnose cancers in early stages and to follow its progression during therapy. Conventional tests require trained personnel, dedicated laboratory equipment and are generally time-consuming. Herein, we propose our developed biosensing platform as a useful tool for a rapid determination of Angiopoietin-2 biomarker directly from patient plasma within 30 minutes, without any sample preparation or dilution. Bloch surface waves supported by one dimensional photonic crystal are exploited to enhance and redirect the fluorescence arising from a sandwich immunoassay that involves Angiopoietin-2. The sensing units consist of disposable and low-cost plastic biochips coated with the photonic crystal. The biosensing platform is demonstrated to detect Angiopoietin-2 in plasma samples at the clinically relevant concentration of 6 ng/mL, with an estimated limit of detection of approximately 1 ng/mL. This is the first Bloch surface wave based assay capable of detecting relevant concentrations of an angiogenic factor in plasma samples. The results obtained by the developed biosensing platform are in close agreement with enzyme-linked immunosorbent assays, demonstrating a good accuracy, and their repeatability showed acceptable relative variations.

JOURNAL ARTICLE

Spicer CD, Jumeaux C, Gupta B, Stevens MMet al., 2018, Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applications., Chem Soc Rev

Peptide- and protein-nanoparticle conjugates have emerged as powerful tools for biomedical applications, enabling the treatment, diagnosis, and prevention of disease. In this review, we focus on the key roles played by peptides and proteins in improving, controlling, and defining the performance of nanotechnologies. Within this framework, we provide a comprehensive overview of the key sequences and structures utilised to provide biological and physical stability to nano-constructs, direct particles to their target and influence their cellular and tissue distribution, induce and control biological responses, and form polypeptide self-assembled nanoparticles. In doing so, we highlight the great advances made by the field, as well as the challenges still faced in achieving the clinical translation of peptide- and protein-functionalised nano-drug delivery vehicles, imaging species, and active therapeutics.

JOURNAL ARTICLE

Winther AK, Fejerskov B, Ter Meer M, Jensen NBS, Dillion R, Schaffer JE, Chandrawati R, Stevens MM, Schultze Kool LJ, Simonsen U, Zelikin ANet al., 2018, Enzyme Prodrug Therapy Achieves Site-Specific, Personalized Physiological Responses to the Locally Produced Nitric Oxide., ACS Appl Mater Interfaces

Nitric oxide (NO) is a highly potent but short-lived endogenous radical with a wide spectrum of physiological activities. In this work, we developed an enzymatic approach to the site-specific synthesis of NO mediated by biocatalytic surface coatings. Multilayered polyelectrolyte films were optimized as host compartments for the immobilized β-galactosidase (β-Gal) enzyme through a screen of eight polycations and eight polyanions. The lead composition was used to achieve localized production of NO through the addition of β-Gal-NONOate, a prodrug that releases NO following enzymatic bioconversion. The resulting coatings afforded physiologically relevant flux of NO matching that of the healthy human endothelium. The antiproliferative effect due to the synthesized NO in cell culture was site-specific: within a multiwell dish with freely shared media and nutrients, a 10-fold inhibition of cell growth was achieved on top of the biocatalytic coatings compared to the immediately adjacent enzyme-free microwells. The physiological effect of NO produced via the enzyme prodrug therapy was validated ex vivo in isolated arteries through the measurement of vasodilation. Biocatalytic coatings were deposited on wires produced using alloys used in clinical practice and successfully mediated a NONOate concentration-dependent vasodilation in the small arteries of rats. The results of this study present an exciting opportunity to manufacture implantable biomaterials with physiological responses controlled to the desired level for personalized treatment.

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von Erlach TC, Bertazzo S, Wozniak MA, Horejs C-M, Maynard SA, Attwood S, Robinson BK, Autefage H, Kallepitis C, Hernandez ADR, Chen CS, Goldoni S, Stevens MMet al., 2018, Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate, NATURE MATERIALS, Vol: 17, Pages: 237-+, ISSN: 1476-1122

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, ADVANCED MATERIALS, Vol: 29, ISSN: 0935-9648

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

Bergholt MS, Albro MB, Stevens MM, 2017, Online quantitative monitoring of live cell engineered cartilage growth using diffuse fiber-optic Raman spectroscopy, BIOMATERIALS, Vol: 140, Pages: 128-137, ISSN: 0142-9612

JOURNAL ARTICLE

Chan WCW, Chhowalla M, Glotzer S, Gogotsi Y, Hafner JH, Hammond PT, Hersam MC, Javey A, Kagan CR, Kataoka K, Khademhosseini A, Kotov NA, Lee S-T, Li Y, Moehwald H, Mulvaney P, Nel AE, Nordlander PJ, Parak WJ, Penner RM, Rogach AL, Schaak RE, Stevens MM, Wee ATS, Willson CG, Fernandez LEE, Weiss PSet al., 2017, Our First and Next Decades at ACS Nano, Publisher: AMER CHEMICAL SOC

OTHER

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

Chandrawati R, Olesen MTJ, Marini TCC, Bisra G, Guex AG, de Oliveira MG, Zelikin AN, Stevens MMet al., 2017, Enzyme Prodrug Therapy Engineered into Electrospun Fibers with Embedded Liposomes for Controlled, Localized Synthesis of Therapeutics, ADVANCED HEALTHCARE MATERIALS, Vol: 6, ISSN: 2192-2640

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, ADVANCED HEALTHCARE MATERIALS, Vol: 6, ISSN: 2192-2640

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Chow A, Stuckey DJ, Kidher E, Rocco M, Jabbour RJ, Mansfield CA, Darzi A, Harding SE, Stevens MM, Athanasiou Tet al., 2017, Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction, STEM CELL REPORTS, Vol: 9, Pages: 1415-1422, ISSN: 2213-6711

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, MACROMOLECULAR RAPID COMMUNICATIONS, Vol: 38, ISSN: 1022-1336

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

Ehademhosseini A, Chan WWC, Chhowalla M, Glotzer SC, Gogotsi Y, Hafner JH, Hammond PT, Hersam MC, Javey A, Kagan CR, Kotov NA, Lee S-T, Li Y, Mohwald H, Mulvaney PA, Nel AE, Parak WJ, Penner RM, Rogach AL, Schaak RE, Stevens MM, Wee ATS, Brinker J, Chen X, Chi L, Crommie M, Dekker C, Farokhzad O, Gerber C, Ginger DS, Irvine DJ, Kiessling LL, Kostarelos K, Landes C, Lee T, Leggett GJ, Liang X-J, Liz-Marzan L, Millstone J, Odom TW, Ozcan A, Prato M, Rao CNR, Sailor MJ, Weiss E, Weiss PSet al., 2017, Nanoscience and Nanotechnology Cross Borders, Publisher: AMER CHEMICAL SOC

OTHER

Ember KJI, Hoeve MA, McAughtrie SL, Bergholt MS, Dwyer BJ, Stevens MM, Faulds K, Forbes SJ, Campbell CJet al., 2017, Raman spectroscopy and regenerative medicine: a review, NPJ REGENERATIVE MEDICINE, Vol: 2, ISSN: 2057-3995

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

Guex AG, Puetzer JL, Armgarth A, Littmann E, Stavrinidou E, Giannelis EP, Malliaras GG, Stevens MMet al., 2017, Highly porous scaffolds of PEDOT:PSS for bone tissue engineering, ACTA BIOMATERIALIA, Vol: 62, Pages: 91-101, ISSN: 1742-7061

JOURNAL ARTICLE

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