Imperial College London

DrJamesArmstrong

Faculty of EngineeringDepartment of Materials

Research Fellow MRC UKRI Innovation Rutherford Fellowship
 
 
 
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james.armstrong

 
 
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G02BRoyal School of MinesSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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29 results found

Ouyang L, Armstrong J, Lin Y, Wojciechowski J, Lee-Reeves C, Hachim D, Zhou K, Burdick JA, Stevens Met al., 2020, Expanding and optimizing 3D bioprinting capabilities using complementary network bioinks, Science Advances, Vol: 6, Pages: 1-13, ISSN: 2375-2548

A major challenge in 3D bioprinting is the limited number of bioinks that fulfill the physiochemical requirements of printing, while also providing a desirable environment for encapsulated cells.Here, we address this limitation by temporarily stabilizing bioinks with a complementary thermo-reversible gelatin network. This strategy enablesthe effective printing of biomaterials that would typically not meet printing requirements, with instrument parameters and structural output largely independent of the base biomaterial. This approach is demonstrated across a library of photo-crosslinkable bioinks derived from natural and synthetic polymers, including gelatin, hyaluronic acid, chondroitin sulfate, dextran, alginate, chitosan, heparin,and poly(ethylene glycol). A range of complex and heterogeneous structures are printed, including soft hydrogel constructs supporting the 3D culture of astrocytes. This highly generalizable methodology expands the palette of available bioinks, allowing the biofabrication of constructs optimized to meet the biological requirements of cell culture and tissue engineering.

Journal article

Nele V, Wojciechowski J, Armstrong J, Stevens Met al., 2020, Tailoring gelation mechanisms for advanced hydrogel applications, Advanced Functional Materials, ISSN: 1616-301X

Journal article

Li C, Ouyang L, Armstrong J, Stevens Met al., 2020, Advances in the fabrication of biomaterials for gradient tissue engineering, Trends in Biotechnology, ISSN: 0167-7799

Natural tissues and organs exhibit an array of spatial gradients, from the polar-ized neural tube during embryonic development to the osteochondral interfacepresent at articulating joints. The strong structure–function relationships inthese heterogeneous tissues have sparked intensive research into the develop-ment of methods that can replicate physiological gradients in engineered tis-sues. In this Review, we consider different gradients present in natural tissuesand discuss their critical importance in functional tissue engineering. Using thisbasis, we consolidate the existing fabrication methods into four categories: addi-tive manufacturing, component redistribution, controlled phase changes, andpostmodification. We have illustrated this with recent examples, highlightedprominent trends in thefield, and outlined a set of criteria and perspectives forgradient fabrication.

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Ouyang L, Armstrong J, Salmeron-Sanchez M, Stevens Met al., 2020, Assembly of living building blocks to engineer complex tissues, Advanced Functional Materials, Vol: 30, Pages: 1-22, ISSN: 1616-301X

The great demand for tissue and organ grafts, compounded by an aging demographic and a shortage of available donors, has driven the development of bioengineering approaches that can generate biomimetic tissues in vitro. Despite the considerable progress in conventional scaffold‐based tissue engineering, the recreation of physiological complexity has remained a challenge. Bottom‐up tissue engineering strategies have opened up a new avenue for the modular assembly of living building blocks into customized tissue architectures. This Progress Report overviews the recent progress and trends in the fabrication and assembly of living building blocks, with a key highlight on emerging bioprinting technologies that can be used for modular assembly and complexity in tissue engineering. By summarizing the work to date, providing new classifications of different living building blocks, highlighting state‐of‐the‐art research and trends, and offering personal perspectives on future opportunities, this Progress Report aims to aid and inspire other researchers working in the field of modular tissue engineering.

Journal article

Watts C, Hanham S, Armstrong J, Ahmad M, Stevens M, Klein Net al., 2020, Microwave dielectric sensing of free-flowing, single, living cells in aqueous suspension, IEEE Journal of Electromagnetics, RF and Microwaves in Medicine and Biology, Vol: 4, Pages: 97-208, ISSN: 2469-7249

Dielectric measurements offer the possibility of highly sensitive detection of physical cell properties, and are of interest for clinical applications due to their non-destructive nature and the lack of need for cell labelling. Here we report sensitive measurements on single, living, free-flowing cells (not electrostatically or dielectrophoretically trapped, cultured or fixed directly on sensing elements) in aqueous medium at ~9.8 GHz taken using a coupled dielectric-split ring resonator assembly. Inductive coupling between the two resonators enabled separation of microfluidic chips from RF connectors and allowed for time-resolved continuous-wave measurements on flowing single cells via the coaxial ports of a dielectric-loaded microwave cavity. Analysis via an equivalent circuit model showed that the novel resonator assembly maintained the permittivity-dependent sensitivity of a split ring resonator while operating at quality factors >1000 with lossy aqueous media (typically ~1900). Using a microfluidic channel with a 300 x 300 μm cross section, at a water-loaded resonant amplitude of ~-22 dB at 0 dBm input power level, shifts in amplitude due to individual cells passing through the sensing region of up to -0.0015 dB were observed. Correlations between averaged amplitude shifts and cell size as well as material properties demonstrate the diagnostic potential of this technique.

Journal article

Seong H, Higgins SG, Penders J, Armstrong JPK, Crowder SW, Moore AC, Sero JE, Becce M, Stevens MMet al., 2020, Size-tunable nanoneedle arrays for influencing stem cell morphology, gene expression and nuclear membrane curvature, ACS Nano, Vol: 14, Pages: 5371-5381, ISSN: 1936-0851

High-aspect-ratio nanostructures have emerged as versatile platforms for intracellular sensing and biomolecule delivery. Here, we present a microfabrication approach in which a combination of reactive ion etching protocols was used to produce high-aspect-ratio, nondegradable silicon nanoneedle arrays with tip diameters that can be finely tuned between 20 and 700 nm. We used these arrays to guide the long-term culture of human mesenchymal stem cells (hMSCs). Notably, we used the nanoneedle tip diameter to control the morphology, nuclear size and F-actin alignment of interfaced hMSCs, and to regulate the expression of nuclear lamina genes, Yes-associated protein (YAP) target genes and focal adhesion genes. These topography-driven changes were attributed to signaling by Rho-family GTPase pathways, differences in the effective stiffness of the nanoneedle arrays and the degree of nuclear membrane impingement, with the latter clearly visualized using focused-ion beam scanning electron microscopy (FIB-SEM). Our approach to design high-aspect-ratio nanostructures will be broadly applicable to design biomaterials and biomedical devices used for long-term cell stimulation and monitoring.

Journal article

Armstrong J, Stevens M, 2020, Using remote fields for complex tissue engineering, Trends in Biotechnology, Vol: 38, Pages: 254-263, ISSN: 0167-7799

Great strides have been taken towards the in vitro engineering of clinically-relevant tissue constructsusing the classic triad of cells, materials and biochemical factors. In this perspective, we highlight ways in which these elements can be manipulated or stimulated using a fourth component: the application of remote fields.This arena has gained great momentum over the last few years, with a recent surge of interest in using magnetic, optical and acoustic fields to guide the organization of cells, materials and growth factors. We summarize recent developments and trends in this arena and then lay out a series of challenges that we believe, if met, could enable the widespread adoption of remote fields in mainstream tissue engineering.

Journal article

Nele V, Schutt CE, Wojciechowski J, Kit-Anan W, Doutch JJ, Armstrong J, Stevens Met al., 2020, Ultrasound-triggered enzymatic gelation, Advanced Materials, Vol: 32, Pages: 1-8, ISSN: 0935-9648

Hydrogels are formed using various triggers, including light irradiation, pH adjustment, heating,cooling or chemical addition. In this report, a new method for forming hydrogels is introduced:ultrasound-triggered enzymatic gelation. Specifically, ultrasound is used as a stimulus to liberateliposomal calcium ions, which then trigger the enzymatic activity of transglutaminase. Theactivated enzyme catalyzes the formation of fibrinogen hydrogels through covalent intermolecularcrosslinking. The catalysis and gelation processes are monitored in real time and both the enzymekinetics and final hydrogel properties are controlled by varying the initial ultrasound exposure time.This technology is extended to microbubble-liposome conjugates, which exhibit a stronger responseto the applied acoustic field and are also used for ultrasound-triggered enzymatic hydrogelation. Tothe best of our knowledge, these results are the first instance in which ultrasound has been used as atrigger for either enzyme catalysis or enzymatic hydrogelation. This approach is highly versatile and Peer reviewed version of the manuscript published in final form at Advanced Materials (2020)2could be readily applied to different ion-dependent enzymes or gelation systems. Moreover, thiswork paves the way for the use of ultrasound as a remote trigger for in vivo hydrogelation.

Journal article

Ouyang L, Armstrong J, Chen Q, Lin Y, Stevens Met al., 2020, Void-free 3D bioprinting for in-situ endothelialization and microfluidic perfusion, Advanced Functional Materials, Vol: 30, ISSN: 1616-301X

Two major challenges of 3D bioprinting are the retention of structural fidelity and efficient endothelialization for tissue vascularization. We address both of these issues by introducinga versatile3D bioprinting strategy, in which a templating bioink is deposited layer-by-layer alongside a matrix bioink to establish void-free multimaterial structures. After crosslinking the matrix phase, the templating phase issacrificedto create a well-defined 3D network of interconnected tubular channels. This void-free 3D printing (VF-3DP) approachcircumvents the traditional concerns of structural collapse, deformation and oxygen inhibition, moreover, it can be readily used to printmaterials that are widely considered “unprintable”. By pre-loading endothelial cells into the templating bioink, the inner surface of the channels can be efficiently cellularized with a confluent endothelial layer. This in-situ endothelializationmethod can be used to produce endothelium with a far greater uniformity than can be achieved using the conventional post-seeding approach. This VF-3DP approach canalsobe extended beyond tissue fabrication and towards customized hydrogel-based microfluidics and self-supported perfusable hydrogel constructs.

Journal article

Gopal S, Chiappini C, Armstrong J, Chen Q, Serio A, Hsu C, Meinert C, Klein TJ, Hutmacher DW, Stevens Met al., 2019, Immunogold FIB-SEM: combining volumetric ultrastructure visualization with 3D biomolecular analysis to dissect cell-environment interactions, Advanced Materials, Vol: 31, Pages: 1-8, ISSN: 0935-9648

Volumetric imaging techniques capable of correlating structural and functional information with nanoscale resolution are necessary to broaden the insight into cellular processes within complex biological systems. The recent emergence of focused ion beam scanning electron microscopy (FIB‐SEM) has provided unparalleled insight through the volumetric investigation of ultrastructure; however, it does not provide biomolecular information at equivalent resolution. Here, immunogold FIB‐SEM, which combines antigen labeling with in situ FIB‐SEM imaging, is developed in order to spatially map ultrastructural and biomolecular information simultaneously. This method is applied to investigate two different cell–material systems: the localization of histone epigenetic modifications in neural stem cells cultured on microstructured substrates and the distribution of nuclear pore complexes in myoblasts differentiated on a soft hydrogel surface. Immunogold FIB‐SEM offers the potential for broad applicability to correlate structure and function with nanoscale resolution when addressing questions across cell biology, biomaterials, and regenerative medicine.

Journal article

Armstrong J, Stevens M, 2019, Emerging technologies for tissue engineering: from gene editing to personalized medicine, Tissue Engineering: Parts A, B, and C, Vol: 25, ISSN: 1937-3341

Technological innovation has been integral to the development of tissue engineering over the last 25 years. Future advances will require the next-generation of tissue engineers to embrace emerging technologies. Here, we discuss four key areas of opportunity in which technology can play a role: biological manipulation, advanced characterization, process automation and personalized medicine. This encompasses key developments in transdifferentiation, gene editing, spatially-resolved -omics and 3D bioprinting. Taken together, we can imagine an idealized future in which computational predictions made by machine learning algorithms are used to programme cells and materials to create personalized tissue constructs within an automated culture system.

Journal article

Li C, Ouyang L, Pence I, Moore A, Lin Y, Winter C, Armstrong J, Stevens Met al., 2019, Buoyancy-driven gradients for biomaterial fabrication and tissue engineering, Advanced Materials, Vol: 31, ISSN: 0935-9648

The controlled fabrication of gradient materials is becoming increasingly important as the next generation of tissue engineering seeks to produce inhomogeneous constructs with physiological complexity. Current strategies for fabricating gradient materials can require highly specialized materials or equipment and cannot be generally applied to the wide range of systems used for tissue engineering. Here, the fundamental physical principle of buoyancy is exploited as a generalized approach for generating materials bearing well‐defined compositional, mechanical, or biochemical gradients. Gradient formation is demonstrated across a range of different materials (e.g., polymers and hydrogels) and cargos (e.g., liposomes, nanoparticles, extracellular vesicles, macromolecules, and small molecules). As well as providing versatility, this buoyancy‐driven gradient approach also offers speed (<1 min) and simplicity (a single injection) using standard laboratory apparatus. Moreover, this technique is readily applied to a major target in complex tissue engineering: the osteochondral interface. A bone morphogenetic protein 2 gradient, presented across a gelatin methacryloyl hydrogel laden with human mesenchymal stem cells, is used to locally stimulate osteogenesis and mineralization in order to produce integrated osteochondral tissue constructs. The versatility and accessibility of this fabrication platform should ensure widespread applicability and provide opportunities to generate other gradient materials or interfacial tissues.

Journal article

Armstrong J, Maynard S, Pence I, Franklin AC, Drinkwater BW, Stevens Met al., 2019, Spatiotemporal quantification of acoustic cell patterning using Voronoi Tessellation, Lab on a Chip, Vol: 19, Pages: 562-573, ISSN: 1473-0189

Acoustic patterning using ultrasound standing waves has recently emerged as a potent biotechnology enabling the remote generation of ordered cell systems. This capability has opened up exciting opportunities, for example, in guiding the development of organoid cultures or the organization of complex tissues. The success of these studies is often contingent on the formation of tightly-packed and uniform cell arrays; however, a number of factors can act to disrupt or prevent acoustic patterning. Yet, to the best of our knowledge, there has been no comprehensive assessment of the quality of acoustically-patterned cell populations. In this report we use a mathematical approach, known as Voronoï tessellation, to generate a series of metrics that can be used to measure the effect of cell concentration, pressure amplitude, ultrasound frequency and biomaterial viscosity upon the quality of acoustically-patterned cell systems. Moreover, we extend this approach towards the characterization of spatiotemporal processes, namely, the acoustic patterning of cell suspensions and the migration of patterned, adherent cell clusters. This strategy is simple, unbiased and highly informative, and we anticipate that the methods described here will provide a systematic framework for all stages of acoustic patterning, including the robust quality control of devices, statistical comparison of patterning conditions, the quantitative exploration of parameter limits and the ability to track patterned tissue formation over time.

Journal article

Armstrong J, Puetzer JL, Serio A, Guex AG, Kapnisi K, Breant A, Zong Y, Assal V, Skaalure S, King O, Murty T, Meinert C, Franklin AC, Bassindale PG, Nichols MK, Terracciano C, Hutmacher DW, Drinkwater BW, Klein TJ, Perriman AW, Stevens MMet al., 2018, Engineering anisotropic muscle tissue using acoustic cell patterning, Advanced Materials, Vol: 30, ISSN: 0935-9648

Tissue engineering has offered unique opportunities for disease modeling and regenerative medicine; however, the success of these strategies is dependent on faithful reproduction of native cellular organization. Here, it is reported that ultrasound standing waves can be used to organize myoblast populations in material systems for the engineering of aligned muscle tissue constructs. Patterned muscle engineered using type I collagen hydrogels exhibits significant anisotropy in tensile strength, and under mechanical constraint, produced microscale alignment on a cell and fiber level. Moreover, acoustic patterning of myoblasts in gelatin methacryloyl hydrogels significantly enhances myofibrillogenesis and promotes the formation of muscle fibers containing aligned bundles of myotubes, with a width of 120–150 µm and a spacing of 180–220 µm. The ability to remotely pattern fibers of aligned myotubes without any material cues or complex fabrication procedures represents a significant advance in the field of muscle tissue engineering. In general, these results are the first instance of engineered cell fibers formed from the differentiation of acoustically patterned cells. It is anticipated that this versatile methodology can be applied to many complex tissue morphologies, with broader relevance for spatially organized cell cultures, organoid development, and bioelectronics.

Journal article

Li C, Armstrong J, Pence I, Kit-Anan W, Puetzer J, Correia Carreira S, Stevens MMet al., 2018, Glycosylated superparamagnetic nanoparticle gradients for osteochondral tissue engineering, Biomaterials, Vol: 176, Pages: 24-33, ISSN: 0142-9612

In developmental biology, gradients of bioactive signals direct the formation of structural transitions in tissue that are key to physiological function. Failure to reproduce these native features in an in vitro setting can severely limit the success of bioengineered tissue constructs. In this report, we introduce a facile and rapid platform that uses magnetic field alignment of glycosylated superparamagnetic iron oxide nanoparticles, pre-loaded with growth factors, to pattern biochemical gradients into a range of biomaterial systems. Gradients of bone morphogenetic protein 2 in agarose hydrogels were used to spatially direct the osteogenesis of human mesenchymal stem cells and generate robust osteochondral tissue constructs exhibiting a clear mineral transition from bone to cartilage. Interestingly, the smooth gradients in growth factor concentration gave rise to biologically-relevant, emergent structural features, including a tidemark transition demarcating mineralized and non-mineralized tissue and an osteochondral interface rich in hypertrophic chondrocytes. This platform technology offers great versatility and provides an exciting new opportunity for overcoming a range of interfacial tissue engineering challenges.

Journal article

Armstrong JP, Stevens MM, 2018, Strategic design of extracellular vesicle drug delivery systems, Advanced Drug Delivery Reviews, Vol: 130, Pages: 12-16, ISSN: 0169-409X

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

Graham AD, Olof SN, Burke MJ, Armstrong JPK, Mikhailova EA, Nicholson JG, Box SJ, Szele FG, Perriman AW, Bayley Het al., 2017, High-Resolution Patterned Cellular Constructs by Droplet-Based 3D Printing., Scientific Reports, Vol: 7, ISSN: 2045-2322

Bioprinting is an emerging technique for the fabrication of living tissues that allows cells to be arranged in predetermined three-dimensional (3D) architectures. However, to date, there are limited examples of bioprinted constructs containing multiple cell types patterned at high-resolution. Here we present a low-cost process that employs 3D printing of aqueous droplets containing mammalian cells to produce robust, patterned constructs in oil, which were reproducibly transferred to culture medium. Human embryonic kidney (HEK) cells and ovine mesenchymal stem cells (oMSCs) were printed at tissue-relevant densities (10(7) cells mL(-1)) and a high droplet resolution of 1 nL. High-resolution 3D geometries were printed with features of ≤200 μm; these included an arborised cell junction, a diagonal-plane junction and an osteochondral interface. The printed cells showed high viability (90% on average) and HEK cells within the printed structures were shown to proliferate under culture conditions. Significantly, a five-week tissue engineering study demonstrated that printed oMSCs could be differentiated down the chondrogenic lineage to generate cartilage-like structures containing type II collagen.

Journal article

Burke M, Armstrong JPK, Goodwin A, Deller RC, Carter BM, Harniman RL, Ginwalla A, Ting VP, Davis SA, Perriman AWet al., 2017, Regulation of Scaffold Cell Adhesion Using Artificial Membrane Binding Proteins, MACROMOLECULAR BIOSCIENCE, Vol: 17, ISSN: 1616-5187

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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

In the past decade, extracellular vesicles(EVs) have emerged as a key cell-free strategy for thetreatment of a range of pathologies, including cancer,myocardial infarction, and inflammatory diseases. Indeed,the field is rapidly transitioning from promising in vitroreports toward in vivo animal models and early clinicalstudies. These investigations exploit the high physicochemicalstability and biocompatibility of EVs as well as theirinnate capacity to communicate with cells via signaltransduction and membrane fusion. This review focuseson methods in which EVs can be chemically or biologicallymodified to broaden, alter, or enhance their therapeuticcapability. We examine two broad strategies, which havebeen used to introduce a wide range of nanoparticles, reporter systems, targeting peptides, pharmaceutics, and functionalRNA molecules. First, we explore how EVs can be modified by manipulating their parent cells, either through genetic ormetabolic engineering or by introducing exogenous material that is subsequently incorporated into secreted EVs. Second,we consider how EVs can be directly functionalized using strategies such as hydrophobic insertion, covalent surfacechemistry, and membrane permeabilization. We discuss the historical context of each specific technology, presentprominent examples, and evaluate the complexities, potential pitfalls, and opportunities presented by different reengineeringstrategies.

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Carreira SC, Armstrong JPK, Okuda M, Seddon AM, Perriman AW, Schwarzacher Wet al., 2016, Synthesis of Cationized Magnetoferritin for Ultra-fast Magnetization of Cells, Jove-Journal of Visualized Experiments, ISSN: 1940-087X

Many important biomedical applications, such as cell imaging and remote manipulation, can be achieved by labeling cells withsuperparamagnetic iron oxide nanoparticles (SPIONs). Achieving sufficient cellular uptake of SPIONs is a challenge that has traditionally beenmet by exposing cells to elevated concentrations of SPIONs or by prolonging exposure times (up to 72 hr). However, these strategies are likelyto mediate toxicity. Here, we present the synthesis of the protein-based SPION magnetoferritin as well as a facile surface functionalizationprotocol that enables rapid cell magnetization using low exposure concentrations. The SPION core of magnetoferritin consists of cobalt-dopediron oxide with an average particle diameter of 8.2 nm mineralized inside the cavity of horse spleen apo-ferritin. Chemical cationization ofmagnetoferritin produced a novel, highly membrane-active SPION that magnetized human mesenchymal stem cells (hMSCs) using incubationtimes as short as one minute and iron concentrations as lows as 0.2 mM.

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Risbridger TAG, Watkins DW, Armstrong JPK, Perriman AW, Anderson JLR, Fermin DJet al., 2016, Effect of Bioconjugation on the Reduction Potential of Heme Proteins, BIOMACROMOLECULES, Vol: 17, Pages: 3485-3492, ISSN: 1525-7797

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Armstrong JPK, Perriman AW, 2016, Strategies for cell membrane functionalization, EXPERIMENTAL BIOLOGY AND MEDICINE, Vol: 241, Pages: 1098-1106, ISSN: 1535-3702

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Armstrong JPK, Burke M, Carter BM, Davis SA, Perriman AWet al., 2016, 3D Bioprinting Using a Templated Porous Bioink, Advanced Healthcare Materials, Vol: 5, Pages: 1724-1730, ISSN: 2192-2640

3D tissue printing with adult stem cells is reported. A novel cell-containing multicomponent bioink is used in a two-step 3D printing process to engineer bone and cartilage architectures.

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Carreira SC, Armstrong JPK, Seddon A, Periman A, Hartley-Davies R, Schwarzacher Wet al., 2016, Ultra-fast stem cell labelling using cationised magnetoferritin, Nanoscale, Vol: 8, Pages: 7474-7483, ISSN: 2040-3372

Magnetic cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) facilitates many important biotechnological applications, such as cell imaging and remote manipulation. However, to achieve adequate cellular loading of SPIONs, long incubation times (24 hours and more) or laborious surface functionalisation are often employed, which can adversely affect cell function. Here, we demonstrate that chemical cationisation of magnetoferritin produces a highly membrane-active nanoparticle that can magnetise human mesenchymal stem cells (hMSCs) using incubation times as short as one minute. Magnetisation persisted for several weeks in culture and provided significant T2* contrast enhancement during magnetic resonance imaging. Exposure to cationised magnetoferritin did not adversely affect the membrane integrity, proliferation and multi-lineage differentiation capacity of hMSCs, which provides the first detailed evidence for the biocompatibility of magnetoferritin. The combination of synthetic ease and flexibility, the rapidity of labelling and absence of cytotoxicity make this novel nanoparticle system an easily accessible and versatile platform for a range of cell-based therapies in regenerative medicine.

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Armstrong JPK, Olof SN, Jakimowicz MD, Hollander AP, Mann S, Davis SA, Miles MJ, Patil AJ, Perriman AWet al., 2015, Cell paintballing using optically targeted coacervate microdroplets, Chemical Science, Vol: 6, Pages: 6106-6111, ISSN: 2041-6520

We present a new approach for the directed delivery of biomolecular payloads to individual cells with high spatial precision. This was accomplished via active sequestration of proteins, oligonucleotides or molecular dyes into coacervate microdroplets, which were then delivered to specific regions of stem cell membranes using a dynamic holographic assembler, resulting in spontaneous coacervate microdroplet–membrane fusion. The facile preparation, high sequestration efficiency and inherent membrane affinity of the microdroplets make this novel “cell paintballing” technology a highly advantageous option for spatially-directed cell functionalization, with potential applications in single cell stimulation, transfection and differentiation.

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Armstrong JPK, Shakur R, Horne JP, Dickinson SC, Armstrong CT, Lau K, Kadiwala J, Lowe R, Seddon A, Mann S, otherset al., 2015, Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue, Nature Communications, Vol: 6, ISSN: 2041-1723

Restricted oxygen diffusion can result in central cell necrosis in engineered tissue, a problemthat is exacerbated when engineering large tissue constructs for clinical application.Here we show that pre-treating human mesenchymal stem cells (hMSCs) with syntheticmembrane-active myoglobin-polymer–surfactant complexes can provide a reservoir ofoxygen capable of alleviating necrosis at the centre of hyaline cartilage. This is achievedthrough the development of a new cell functionalization methodology based onpolymer–surfactant conjugation, which allows the delivery of functional proteins to the hMSCmembrane. This new approach circumvents the need for cell surface engineering usingprotein chimerization or genetic transfection, and we demonstrate that the surface-modifiedhMSCs retain their ability to proliferate and to undergo multilineage differentiation. Thefunctionalization technology is facile, versatile and non-disruptive, and in addition to tissueoxygenation, it should have far-reaching application in a host of tissue engineering andcell-based therapies.

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Brown P, Khan AM, Armstrong JPK, Perriman AW, Butts CP, Eastoe Jet al., 2012, Magnetizing DNA and proteins using responsive surfactants, Advanced Materials, Vol: 24, Pages: 6244-6247

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Guijt RM, Armstrong JP, Candish E, Lefleur V, Percey WJ, Shabala S, Hauser PC, Breadmore MCet al., 2011, Microfluidic chips for capillary electrophoresis with integrated electrodes for capacitively coupled conductivity detection based on printed circuit board technology, Sensors and Actuators B: Chemical, Vol: 159, Pages: 307-313

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de Lacy Costello BPJ, Armstrong J, Jahan I, Ratcliffe NMet al., 2010, Fine control and selection of travelling waves in Inorganic Pattern Forming Reactions, Theoretical and Technological Advancements in Nanotechnology and Molecular Computation: Interdisciplinary Gains: Interdisciplinary Gains, Pages: 184-184

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