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

317 results found

Albro MB, Bergholt MS, St-Pierre JP, Guitart AV, 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 REGENERATIVE MEDICINE, Vol: 3, ISSN: 2057-3995

JOURNAL ARTICLE

Armstrong JPK, Stevens MM, 2018, Strategic design of extracellular vesicle drug delivery systems., Adv Drug Deliv Rev

Extracellular vesicles (EVs), sub-micron vectors used in intercellular communication, have demonstrated great promise as natural drug delivery systems. Recent reports have detailed impressive in vivo results from the administration of EVs pre-loaded with therapeutic cargo, including small molecules, nanoparticles, proteins and oligonucleotides. These results have sparked intensive research interest across a huge range of disease models. There are, however, enduring limitations that have restricted widespread clinical and pharmaceutical adoption. In this perspective, we discuss these practical and biological concerns, critically compare the relative merit of EVs and synthetic drug delivery systems, and highlight the need for a more comprehensive understanding of in vivo transport and delivery. Within this framework, we seek to establish key areas in which EVs can gain a competitive advantage in order to provide the tangible added value required for widespread translation.

JOURNAL ARTICLE

Barriga HMG, Holme MN, Stevens MM, 2018, Cubosomes; the next generation of smart lipid nanoparticles?, Angew Chem Int Ed Engl

Cubosomes are highly stable nanoparticles formed from the lipid cubic phase and stabilized by a polymer based outer corona. Lipid cubic phases consist of a single lipid bilayer which forms a continuous periodic membrane lattice structure with pores formed by two interwoven water channels. Cubosome composition can be tuned to engineer pore sizes or include bioactive lipids, the polymer outer corona can be used for targeting and they are highly stable under physiological conditions. The structure provides a significantly higher membrane surface area for loading of membrane proteins and small drug molecules than liposomes. Due to recent advances, they can be engineered in vitro in both bulk and nanoparticle formats with applications including drug delivery, membrane bioreactors, artificial cells and biosensors. This review outlines recent advances in cubosome technology enabling their application and provides guidelines for the rational design of new systems for biomedical applications.

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

Elsharkawy S, Al-Jawad M, Pantano MF, Tejeda-Montes E, Mehta K, Jamal H, Agarwal S, Shuturminska K, Rice A, Tarakina N, Wilson RM, Bushby AJ, Alonso M, Rodriguez-Cabello JC, Barbieft E, Hernandez ADR, Stevens MM, Pugno NM, Anderson P, Mata Aet al., 2018, Protein disorder-order interplay to guide the growth of hierarchical mineralized structures, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723

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, ADVANCED MATERIALS, Vol: 30, ISSN: 0935-9648

JOURNAL ARTICLE

Holme MN, Rana S, Barriga HMG, Kauscher U, Brooks NJ, Stevens MMet al., 2018, A Robust Liposomal Platform for Direct Colorimetric Detection of Sphingomyelinase Enzyme and Inhibitors., ACS Nano

The enzyme sphingomyelinase (SMase) is an important biomarker for several diseases such as Niemann Pick's, atherosclerosis, multiple sclerosis, and HIV. We present a two-component colorimetric SMase activity assay that is more sensitive and much faster than currently available commercial assays. Herein, SMase-triggered release of cysteine from a sphingomyelin (SM)-based liposome formulation with 60 mol % cholesterol causes gold nanoparticle (AuNP) aggregation, enabling colorimetric detection of SMase activities as low as 0.02 mU/mL, corresponding to 1.4 pM concentration. While the lipid composition offers a stable, nonleaky liposome platform with minimal background signal, high specificity toward SMase avoids cross-reactivity of other similar phospholipases. Notably, use of an SM-based liposome formulation accurately mimics the natural in vivo substrate: the cell membrane. We studied the physical rearrangement process of the lipid membrane during SMase-mediated hydrolysis of SM to ceramide using small- and wide-angle X-ray scattering. A change in lipid phase from a liquid to gel state bilayer with increasing concentration of ceramide accounts for the observed increase in membrane permeability and consequent release of encapsulated cysteine. We further demonstrated the effectiveness of the sensor in colorimetric screening of small-molecule drug candidates, paving the way for the identification of novel SMase inhibitors in minutes. Taken together, the simplicity, speed, sensitivity, and naked-eye readout of this assay offer huge potential in point-of-care diagnostics and high-throughput drug screening.

JOURNAL ARTICLE

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

JOURNAL ARTICLE

Kapnisi M, Mansfield C, Marijon C, Guex AG, Perbellini F, Bardi I, Humphrey EJ, Puetzer JL, Mawad D, Koutsogeorgis DC, Stuckey DJ, Terracciano CM, Harding SE, Stevens MMet al., 2018, Auxetic Cardiac Patches with Tunable Mechanical and Conductive Properties toward Treating Myocardial Infarction, ADVANCED FUNCTIONAL MATERIALS, Vol: 28, ISSN: 1616-301X

JOURNAL ARTICLE

Keane TJ, Horejs C-M, Stevens MM, 2018, Scarring vs. functional healing: Matrix-based strategies to regulate tissue repair, ADVANCED DRUG DELIVERY REVIEWS, Vol: 129, Pages: 407-419, ISSN: 0169-409X

JOURNAL ARTICLE

Li C, Armstrong JPK, Pence IJ, Kit-Anan W, Puetzer JL, Carreira SC, Moore AC, Stevens MMet al., 2018, Glycosylated superparamagnetic nanoparticle gradients for osteochondral tissue engineering, BIOMATERIALS, Vol: 176, Pages: 24-33, ISSN: 0142-9612

JOURNAL ARTICLE

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

JOURNAL ARTICLE

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

Reznikov N, Bilton M, Lari L, Stevens MM, Kroger Ret al., 2018, Fractal-like hierarchical organization of bone begins at the nanoscale, SCIENCE, Vol: 360, Pages: 507-+, ISSN: 0036-8075

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

Sang T, Li S, Ting H-K, Stevens MM, Becer CR, Jones JRet al., 2018, Hybrids of Silica/Poly(caprolactone coglycidoxypropyl trimethoxysilane) as Biomaterials, CHEMISTRY OF MATERIALS, Vol: 30, Pages: 3743-3751, ISSN: 0897-4756

JOURNAL ARTICLE

Sigmundsson K, Ojala JRM, Öhman MK, Österholm A-M, Moreno-Moral A, Domogatskaya A, Chong LY, Sun Y, Chai X, Steele JAM, George B, Patarroyo M, Nilsson A-S, Rodin S, Ghosh S, Stevens MM, Petretto E, Tryggvason Ket al., 2018, Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice., Matrix Biol, Vol: 70, Pages: 5-19

The efficacy of islet transplantation for diabetes treatment suffers from lack of cadaver-derived islets, islet necrosis and long transfer times prior to transplantation. Here, we developed a method for culturing mouse and human islets in vitro on α5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1-3 cells in thickness and remained normoxic and functional for at least 7 days in culture. In contrast, spherical islets kept in suspension developed hypoxia and central necrosis within 16 h. Transplantation of 110-150 mouse islets cultured on α5-laminin-coated polydimethylsiloxane membranes for 3-7 days normalized blood glucose already within 3 days in mice with streptozotocin-induced diabetes. RNA-sequencing of isolated and cultured mouse islets provided further evidence for the adhesion and spreading achieved with α5-laminin. Our results suggest that use of such in vitro expanded islets may significantly enhance the efficacy of islet transplantation treatment for diabetes.

JOURNAL ARTICLE

Spicer CD, Jumeaux C, Gupta B, Stevens MMet al., 2018, Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applications, CHEMICAL SOCIETY REVIEWS, Vol: 47, Pages: 3574-3620, ISSN: 0306-0012

JOURNAL ARTICLE

Spicer CD, Pashuck ET, Stevens MM, 2018, Achieving Controlled Biomolecule-Biomaterial Conjugation., Chem Rev

The conjugation of biomolecules can impart materials with the bioactivity necessary to modulate specific cell behaviors. While the biological roles of particular polypeptide, oligonucleotide, and glycan structures have been extensively reviewed, along with the influence of attachment on material structure and function, the key role played by the conjugation strategy in determining activity is often overlooked. In this review, we focus on the chemistry of biomolecule conjugation and provide a comprehensive overview of the key strategies for achieving controlled biomaterial functionalization. No universal method exists to provide optimal attachment, and here we will discuss both the relative advantages and disadvantages of each technique. In doing so, we highlight the importance of carefully considering the impact and suitability of a particular technique during biomaterial design.

JOURNAL ARTICLE

Winther AK, Fejerskov B, ter Meer M, Jensen NBS, Dillison R, Schaffer JE, Chandrawati R, Stevens MM, Kool LJS, Simonsen U, Zelikin ANet al., 2018, Enzyme Prodrug Therapy Achieves Site-Specific, Personalized Physiological Responses to the Locally Produced Nitric Oxide, ACS APPLIED MATERIALS & INTERFACES, Vol: 10, Pages: 10741-10751, ISSN: 1944-8244

JOURNAL ARTICLE

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

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