Global Medical Discovery features paper: Nanostructured material formulated acrylic bone cements with enhanced drug release

Significance Statement

Current commercial polymethylmethacrylate (PMMA) based antibiotics-loaded bone cements exhibit very low drug release as most of the antibiotics are embedded inside the polymerized bone cement.  This results in a rapid decrease in antimicrobial activity below the effective therapeutic level within one to several days. To increase the therapeutic window to several weeks for reducing the risk of post-operative joint infection, mesoporous silica nanoparticles (MSN) functional bone cement was developed to enable a sustained release of antibiotics.

Our results show that the novel formulation can be designed to tailor a desired release profile, e.g. up to 70% drug release for several weeks in comparison with commercial bone cement showing 10% or lower drug release and peak concentration only on day one.  MSN with uniform nano-porous channels built up effective diffusion nano-networks which enabled the drug molecules to be released sustainably. Moreover, the mechanical properties of bone cements were well preserved in the presence of MSN in formulation even after drug release.

This formulation is expected to deliver the next generation bone cement with tailor-designed antibiotics release profiles and prolonged antibacterial activity.  The key commercial advantages to potential bone cement manufacturers and end users are sustained antibiotics release, reduction in standard antibiotics dosage, minimised use of intravenous doses and creating new opportunities to use other benefit ingredient for local targeted delivery.  Once commercialized, the socio-economic impact and savings in medical resources and costs are expected to be significant as the risk of post-operative infections can be reduced.       

About The Author

Reginald Tan received PhD degree from University of Cambridge in 1989. He is Director (Research) of the Institute of Chemical and Engineering Sciences (ICES, Singapore) and concurrently a Professor in the Department of Chemical and Bimolecular Engineering, National University of Singapore. His current research is in crystallisation science and modelling, and formulation sciences.

About The Author

Shoucang SHEN obtained PhD degree from National University of Singapore at 2001. Currently, he is a senior scientist in Institute of Chemical and Engineering Sciences (ICES, Singapore). His research interest includes formulation of poorly soluble drugs and controlled release of active ingredients, as well as the exploration of nanotechnology.

About The Author

Ng Wai Kiong obtained PhD degree from National University of Singapore and Diplom Ingenieur from Technical University of Clausthal, Germany. He is Team Leader (Formulation Sciences) in the Crystallisation and Particle Sciences Division, Institute of Chemical and Engineering Sciences (ICES, Singapore).

Reference

Mater Sci Eng C Mater Biol Appl. 2016 ;58:233-41.

Shen SC¹, Ng WK², Dong YC², Ng J², Tan RB³.

Show Affiliations

¹Institute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), 1 Pesek Road, Jurong Island, Singapore 627833, Singapore. Electronic address: shen_shoucang@ices.a-star.edu.sg.

²Institute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), 1 Pesek Road, Jurong Island, Singapore 627833, Singapore.

³Institute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), 1 Pesek Road, Jurong Island, Singapore 627833, Singapore; Department of Chemical and Biomolecular Engineering, The National University of Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore. Electronic address: reginald_tan@ices.a-star.edu.sg.

Abstract

To improve antibiotic properties, poly(methyl methacrylate) (PMMA)-based bone cements are formulated with antibiotic and nanostructured materials, such as hydroxyapatite (HAP) nanorods, carbon nanotubes (CNT) and mesoporous silica nanoparticles (MSN) as drug carriers. For nonporous HAP nanorods, the release of gentamicin (GTMC) is not obviously improved when the content of HAP is below 10%; while the high content of HAP shows detrimental to mechanical properties although the release of GTMC can be substantially increased. As a comparison, low content of hollow nanostructured CNT and MSN can enhance drug delivery efficiency. The presence of 5.3% of CNT in formulation can facilitate the release of more than 75% of GTMC in 80 days, however, its mechanical strength is seriously impaired. Among nanostructured drug carriers, antibiotic/MSN formulation can effectively improve drug delivery and exhibit well preserved mechanical properties. The hollow nanostructured materials are believed to build up nano-networks for antibiotic to diffuse from the bone cement matrix to surface and achieve sustained drug release. Based on MSN drug carrier in formulated bone cement, a binary delivery system is also investigated to release GTMC together with other antibiotics.

Copyright © 2015 Elsevier B.V. All rights reserved.

Go To Materials Science and Engineering: C

Global Medical Discovery features paper: Direct Electron Transfer of Enzymes in a Biologically Assembled Conductive Nanomesh Enzyme Platform

Significance Statement

Recently, wearable biomedical sensors that enable non-invasive monitoring of health condition have been attracting drastically increasing interest. In particular, a non-invasive device that can measure glucose levels in bio-fluid such as tear, saliva, and sweat is regarded as one of the most promising biosensor platforms for future healthcare application. Bio-fluids have been known to contain informative indicators (i.e., glucose). Moreover, they are naturally and continuously excreted from the human body. Therefore, a wearable glucose sensor that is placed or attached on a body could continuously measure glucose levels in a non-invasive manner and real rime. Thus, patients do not have to prick their fingers for blood collection every time, and it would ultimately reduce the pain of diabetes patients and prevent the possible secondary infection.

Current blood glucometers best work for measuring glucose level in blood. Meanwhile, the glucose concentration in tear, saliva, or sweat, are about 20~100 times lower than that in blood glucose. In addition, at this low glucose level, the interfering redox species, such as ascorbic acid, uric acid or acetaminophen, greatly influence the sensor performance. Therefore, to realize non-invasive and wearable monitoring of glucose levels, the flexible biosensor platform must own much more enhanced sensitivity and selectivity than current blood glucometers. Furthermore, the biosensor has to be non-toxic for wearable purpose. Considering all these requirements for wearable biomedical sensors, the 3^rd generation biosensor platform that employs the direct-electron-transfer (DET) mechanism of enzymes would be a promising candidate. Owing to the direct electrical communication with enzymes at the negative potential range, being apart from the oxidation potential of interfering redox species by -600 mV, the sensor can achieve both high sensitivity at sub-millimolar level and excellent selectivity on target analytes. Moreover, since the electrode and the enzyme directly communicate, no chemical mediator is required. Therefore, DET obviates the toxicity issues involved in the chemicals.

To achieve efficient DET of enzymes, realizing intimate electrical contacts with redox biomolecules at nanoscale is of crucial importance. In this work, we report a new approach that enables highly facilitated biomolecular electron transfer with unprecedented versatility and applicability. Enzymes are intimately interfaced with a conductive nanomesh made of single-walled carbon nanotubes (SWNTs) via a rationally designed interlayer. SWNTs are hydro-dynamically assembled into a conductive nanomesh by using a filamentous phage that shows a strong binding affinity toward SWNTs. The nanostructure of the nanomesh is extremely well controlled over large area. The filamentous phage controls the nanostructure and at the same time serves as a biological glue to stabilize the nanomesh structure in solution. The conductive nanomesh is then transferred onto metallic electrodes to produce a nanostructured electrical platform for biomolecular direct electron transfer (DET). The conductive nanomesh is then rationally interfaced with enzymes by using a polyelectrolyte layer with appropriate charge characteristics. This interfacial layer enables both intimate nanoscale electrical contacts to biomolecules for facilitated electron transfer and highly porous nanostructures for high sensitivity.

Using this layered conductive nanomesh enzyme platform, we successfully achieve DET for eight different enzymes (including glucose oxidase and lactate oxidase) with various types of catalytic activities. The direct electrical communication of enzymes on the conductive nanomesh enables not only the high sensitivity at sub-millimolar level of target (i.e, glucose or lactate), but also the high selectivity of the sensor due to the operation at negative potential range. We further demonstrate a flexible DET-based glucose-biosensor, for the first time, to the best of our knowledge. The electron transfer efficiency and sensitivity of these flexible integrated biosensors are comparable to those obtained using commercialized screen printed electrodes.

We believe that the biologically assembled conductive nanomesh enzyme platform presents a promising solution for future health-monitoring systems. 

About The Author

Dr. Hyunjung Yi received her B.S. and M.S. degrees from Pohang University of Science and Technology (POSTECH), Pohang, Korea, in the department of Material Science and Engineering and Ph. D. degree from Massachusetts Institute of Technology (MIT), Cambridge, USA in the department of Material Science and Engineering in 2001, 2003, and 2011, respectively.

Dr. Hyungjung Yi joined Korea Institute of Science and Technology (KIST), Seoul, Korea, in 2003 as a research scientist and is currently a Principal Investigator and a Senior Research Scientist.

Dr. Hyunjung Yi’s research focuses on developing nano-bio hybrid materials for wearable biosensors, electronics, tactile sensors, and flexible energy devices. Biotechnology to genetically engineer biomaterials and processes to assemble and fabricate nano-bio hybrid are also being developed.

About The Author

Dr. Seung-Woo Lee received B.E. in Fine chemical engineering & Applied chemistry at Chungnam National University in 2006, and Ph.D. in chemical and biomolecular engineering at University of Nebraska-Lincoln in 2013, respectively.

He joined Dr. Hyunjung Yi’s Lab at Korea Institute of Science and Technology (KIST) in 2014.

His research mainly focuses on the electrochemical biosensor, wearable/flexible nano-bio electronics, non-destructively assembly of nano-bio hybrid biosensing materials, and electrochemical bio-energy generation.

Reference

Adv Mater. 2016 Feb;28(8):1577-84.

Lee SW¹, Lee KY¹, Song YW¹, Choi WK², Chang J¹, Yi H¹.

Show Affiliations

¹Post-Silicon Semiconductor Institute, Korea Institute of Science and Technology, Seoul, 136-791, Republic of Korea.

²Materials and Life Science Research Division, Korea Institute of Science and Technology, Seoul, 136-791, Republic of Korea.

 

Abstract

Nondestructive assembly of a nanostructured enzyme platform is developed in combination of the specific biomolecular attraction and electrostatic coupling for highly efficient direct electron transfer (DET) of enzymes with unprecedented applicability and versatility. The biologically assembled conductive nanomesh enzyme platform enables DET-based flexible integrated biosensors and DET of eight different enzyme with various catalytic activities.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

 

Go To Advanced Materials 

Global Medical Discovery features paper: Synergism of Water Shock and a Biocompatible Block Copolymer Potentiates the Antibacterial Activity of Graphene Oxide

Significance Statement

There is an urgent need to find alternative routes to control the spreading of antibiotics-resistant bacteria. Graphene and its water-soluble form graphene oxide (GO) were previously shown to be promising antibacterial agents. However, their antibacterial activity was relatively low and they show toxicity to human cells at high dose of usage. This study demonstrated a new strategy for significantly enhancing the antibacterial activity of graphene oxide. It showed that graphene oxide can kill 99% of bacteria when mixed with a human-friendly detergent in salt-reduced water. Further, the mixture of graphene oxide and Pluronic displays over 50% lower toxicity to human skin cells than the effect of graphene oxide alone. The developed strategy relies on the combination of two effects. The first effect is coming from the water itself. Bacteria inevitably undergo swelling when faced with salt-reduced water which puts a stress on bacterial envelope due to occurrence of microscopic damages. The second effect comes from pluronic; a bio-friendly polymer widely used in drug formulations and food applications. Pluronic increases the stability of graphene oxide in solution and also helps graphene oxide to interact with bacteria better by surrounding the bacterial cells more effectively. Water and detergents are undoubtedly the most common cleaning agents. This study may open the door for graphene oxide to be a widespread cleaning agent for fighting bacteria.

 

About The Author

Yuan Chen received his BEng in Chemical Engineering and MEng in Biochemical Engineering from Tsinghua University. He obtained his PhD in Chemical Engineering at Yale University in 2005. He is currently a Professor at School of Chemical and Biomolecular Engineering (CBE), The University of Sydney. He joined the School of Chemical and Biomedical Engineering in Nanyang Technological University (NTU) in Singapore as an Assistant Professor in 2005. He was promoted to a tenured Associate Professor in 2010. He was visiting Associate Professor at Brown University in 2010 and visiting Chair Professor at Tianjin University of Technology in China 2011-2015. He served as Head of CBE Division in NTU from July 2011 to June 2014. He received an Excellence in Review Award from CARBON in 2015, a Young Scientist Award from the Singapore National Academy of Science in 2011, a Tan Chin Tuan Exchange Fellowship in Engineering in 2010, and JSPS exchange award in 2009. He is currently associate editor for Carbon (Elsevier), editorial board member for Nanomaterials, and Heliyon (Elsevier).  His research focuses on developing scalable chemical processes to synthesize carbon nanomaterials with well-defined nanoscale structures, assembling nanoscale carbon nanomaterials into functional macroscale systems, and utilizing these novel materials for sustainable energy, environmental and biomedical applications.

About The Author

Enis Karahan earned BSc double-degree in Chemical Engineering and Molecular Biology & Genetics from İstanbul Technical University. He received his MSc in Materials Science and Engineering at Koç University. Holding Singapore International Graduate Award (SINGA), he currently pursues his PhD studies in Bioengineering at Nanyang Technological University and Singapore Institute of Manufacturing Technologies of A*STAR. In addition to his academic experience, he also has an industrial background majorly gained in an R&D department of a textile company focused on polymer technologies. His expertise covers a broad spectrum of materials science including self-assembly of multilayered surface coatings, noncovalent functionalization of nanoparticles, and antibacterial, biomedical, and environmental applications of carbon-based nanocomposites to name a few. To date, he has over ten publications in peer-reviewed journals on his account. 

 

Journal Reference

Small. 2016 Feb;12(7):951-62.

Karahan HE^1,2, Wei L¹, Goh K¹, Wiraja C¹, Liu Z¹, Xu C^1,3, Jiang R¹, Wei J², Chen Y^1,4.

Show Affiliations

1. School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637459, Singapore.
2. Singapore Institute of Manufacturing Technology (SIMTech), Singapore, 638075, Singapore.
3. NTU-Northwestern Institute of Nanomedicine, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.
4. School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, 2006, Australia.

 

Abstract

Graphene oxide (GO) is promising in the fight against pathogenic bacteria. However, the antibacterial activity of pristine GO is relatively low and concern over human cytotoxicity further limits its potential. This study demonstrates a general approach to address both issues. The developed approach synergistically combines the water shock treatment (i.e., a sudden decrease in environmental salinity) and the use of a biocompatible block copolymer (Pluronic F-127) as a synergist co-agent. Hypoosmotic stress induced by water shock makes gram-negative pathogens more susceptible to GO. Pluronic forms highly stable nanoassemblies with GO (Pluronic-GO) that can populate around bacterial envelopes favoring the interactions between GO and bacteria. The antibacterial activity of GO at a low concentration (50 μg mL(-1) ) increases from <30% to virtually complete killing (>99%) when complemented with water shock and Pluronic (5 mg mL(-1) ) at ≈2-2.5 h of exposure. Results suggest that the enhanced dispersion of GO and the osmotic pressure generated on bacterial envelopes by polymers together potentiate GO. Pluronic also significantly suppresses the toxicity of GO toward human fibroblast cells. Fundamentally, the results highlight the crucial role of physicochemical milieu in the antibacterial activity of GO. The demonstrated strategy has potentials for daily-life bacterial disinfection applications, as hypotonic Pluronic-GO mixture is both safe and effective.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Go To Small.

 

Global Medical Discovery features paper: Development of localized surface plasmon resonance biosensors for the detection of Brettanomyces bruxellensis in wine

About The Author

Marisa Manzano was born in Udine, Italy. She got the degree in Natural Sciences at University of Padua. She was researcher in Food Microbiology at the University of Udine at the Department of Food Science from 1990 till 2005. Since 2005 Associate Professor at University of Udine teaching: Molecular Biology Techniques, Biotechnology of Microorganisms, Genetic of Microorganisms, Selection and Use of Enological Yeasts in the degree course of Food Science and Technology and Viticulture and Enology. She is Member of Committees: Academic Collegiate of Doctorate Research, Didactic Committee, State Exam Commission; member of the Committee “Quality System in the  laboratory of Microbiology” (UNICHIM). Co-author of a patent – detection of Listeria monocytogenes by PCR, 1996, C12Q. She has long experience in Microbiology and Molecular Biology. Now working on the development of DNA probes for the construction of biosensors for the detection of pathogens. She was invited speaker in various international conferences with talks about rapid detection of pathogens using molecular methods or biosensors. Author of  271 publications including papers/book chapter/abstracts and posters.

About The Author

Priya Vizzini was born in India in 1985. She obtained bachelor’s degree in Biomedical Laboratory Technician at the University of Udine (Italy) in 2011. She won an Erasmus grant to spend 5 months at Troyes University of technology (France) working  on biological applications of  QCM and Localized Surface Plasmon Resonance biosensor under the supervision of the Prof. Rodica Elena Ionescu. She got the master’s degree in Plant and Animal Biotechnology in 2014 at the University of Udine (Italy). In december 2015 she was a selected speaker at the “2^th PARMA NANO-DAY”scientific workshop for the session agribusiness, ambient and biotechnology at Parma University. At present she collaborates in the Department of Agricultural, Food, Environmental and Animal science  in University of Udine. She works on the development of molecular biology methods (PCR, Nested-PCR, DGGE/ TTGE and blotting techniques) for the detection of pathogens in food-beverage and on the evaluation of sterilization systems for private companies. 

About The Author

Kun Jia received his B.S. and M.S. degree in Chemistry from University of Electronic Science and Technology of China (UESTC) in 2007 and 2010, respectively. He obtained his Ph.D. degree from Laboratory of Nanotechnology and Instrumentation Optics (LNIO) at University of Technology of Troyes (UTT) in France under the supervision of Prof. Elena Rodica IONESCU at the end of 2013. In March 2014, Dr. JIA joined the School of Microelectronics and Solid State Electronics of UESTC as an associate professor in Chemistry. His current research interests lie in the field of plasmonic controlled polymer fluorescence, optical (bio)chemical sensors on flexible substrate, and synthesizing of advanced optofunctional polymeric nanocomposites.    

About The Author

Pierre-Michel Adam has obtained his PhD in Physics in 1995 (Université de Bourgogne), and is at present Full Professor at the Université de Technologie de Troyes (ICD-LNIO). Title of his PhD is “Photon Scanning Tunneling Microscope (PSTM) with a polychromatic incoherent light source. Near-field investigation of test samples and surface plasmons.” In january 1995, P.M. Adam has joined the Universite de Technologie de Troyes as an Assistant Professor and has been appointed Full professor in February 2003. His fields of research are near-field microscopy and spectroscopy, surface plasmons, surface enhanced Raman scattering. He is currently in charge of a research group “Nanospectroscopy” at the ICD-LNIO. He is vice-president of a European network COST action MP1302 “Nanospectroscopy”. He is author/coauthor of 76 publications in international journals. He is/has been the supervisor of 16 PhD thesis. 

About The Author

Rodica Elena Ionescu earned one Ph.D. degree from the Ben-Gurion University of Negev, Israel in Biotechnological Engineering in 2004 and a second Ph.D. degree in Chemistry, from the University of Bucharest, in 2007. She has performed three post-doctoral positions in France in the field of electrochemical biosensors. Between February-October 2008, Dr. Ionescu was a researcher fellow at the National Nanotechnology Laboratory, Lecce (Italy) working on impedimetric cell-chips based interdigitated microlectrodes. In November 1^st 2008, Dr. Ionescu joined the Université de Technologie de Troyes (UTT) as an Assistant Professor, becoming a member of the Laboratoire de Nanotechnologie et d’Instrumentation Optique (LNIO). In December 4^th 2009, Dr. Ionescu obtained the Habilitation Title for conducting independent research (HDR) equivalent to an Associate Professor position. Thanks to the obtained research grants, Dr. Ionescu developed novel acoustic and optical platforms for ultrasensitive detection of biomolecules and pesticides. In 2012, Dr. Ionescu was awarded with a national OSEO Innovation grant. Between April 1^st 2014 to March 30, 2015 Dr. Ionescu was the research manager of a Proof-of Concept (POC) Grant-NRF-POC 002-026 supported by the Singapore National Research Foundation concerning the Electrochemical lateral flow biosensor detection and quantification of Dengue virus in whole blood at the Nanyang Technological University, School of Materials Science and Engineering under an international CREATE-NTU-HUJ-BGU program. Her current research activities include the development of multi-analyte biosensing platforms, specific (bio)functionalization of surfaces, atomic force microscopy nanopipette applications, controllable synthesis of nanoparticle, evaluation of nanoparticles and water pollutants toxicity to living cells and microorganisms. She has published over 40 pre-reviewed articles, 4 book chapters and 7 patents with 9 extensions. 

Journal Reference

Sensors and Actuators B: Chemical, Volume 223, February 2016, Pages 295–300 .

Marisa Manzano¹, Priya Vizzini¹,Kun Jia^2,3,Pierre-Michel Adam²,Rodica Elena Ionescu² 

Show Affiliations

1. Department of Food Science, University of Udine, via Sondrio 2/A, 33100 Udine, Italy
2. Laboratoire de Nanotechnologie et d’Instrumentation Optique, Institute Charles Delaunay, Universite’ de Technologie de Troyes, UMR CNRS 6281, 12 Rue Marie-Curie, CS 42060, 10004 Troyes Cedex, France
3. School of Microelectronics and Solid-State Electronics, University of Electronic Science and Technology of China, 610054 Chengdu, China

Abstract

Incident light interacting with noble-metal nanoparticles with smaller sizes than the wavelength of the incident light induces localized surface plasmon resonance (LSPR). In this work a gold nanostructured surface was used for the immobilization of a 5′ end Thiol modified DNA probe to develop a LSPR nanobiosensor for the detection of the spoiler wine yeast Brettanomyces bruxellensis. Gold was evaporated to obtain a gold thickness of 4 nm. DNA (2 μL) from the target microorganism and the negative control at various concentrations were used to test the specificity and sensitivity of the LSPR technique. Changes in the optical properties of the nanoparticles due to DNA-probe binding are reflected in the shift of LSPR extinction maximum (λ_max). The results obtained using as target microorganism B. bruxellensis, and as negative control Saccharomyces cerevisiae demonstrated the specificity of both the DNA-probe and the protocol. The LSPR spectrophotometry technique detects 0.1 ng/μL DNA target confirming the possibility to utilize this system for the detection of pathogen microorganisms present in low amount in food and beverage samples.

Go To Sensors and Actuators B: Chemical

 

Scanning Nanospin Ensemble Microscope for Nanoscale Magnetic and Thermal Imaging

Significance Statement

Scanning probe microscopy techniques provide invaluable access to the nanoworld, enabling measurement of local topographic, electronic, optical and magnetic properties depending on the probe used. The emergence of spin-based quantum probes opens up new imaging modalities that can be combined in a single instrument. Here we introduce a “scanning nano-spin ensemble microscope”, in which the microscope probe consists of a small ensemble of optically active quantum spins hosted in a diamond nanocrystal. We illustrate the practicality and versatility of this approach by performing nanoscale imaging of static and fluctuating magnetic fields as well as thermal imaging, at room temperature with typical acquisition times of an hour per image. This opens up new opportunities for nanoscale investigation of a wide variety of materials and phenomena, including in biological settings.

About The Author

Jean-Philippe Tetienne was born in France in 1987. He received his master’s degree in electrical engineering from the Ecole Normale Superieure de Cachan, France, in 2011. During his master’s, he carried out two research projects in the field of nanophotonics, with Dr Raffaele Colombelli at the University of Paris-Sud, and then with Prof Federico Capasso at Harvard University. In 2014, he received his PhD in physics from the Ecole Normale Superieure de Cachan, where, under the supervision of Dr Vincent Jacques, he developed a new type of scanning probe microscope based on a single spin quantum sensor. In particular, he used this microscope to study domain walls in ultrathin ferromagnetic wires, which has led to the discovery of light-assisted domain wall dragging. In 2015, he joined the group of Prof Lloyd Hollenberg at the University of Melbourne, where he is currently working as a postdoctoral fellow on sensing and imaging using diamond quantum sensors. His research interests include nanophotonics, quantum sensing, scanning probe microscopy, and nanomagnetism.

Journal Reference

Nano Lett. 2016 Jan 13;16(1):326-33.

Tetienne JP^1,2, Lombard A^1,3, Simpson DA⁴, Ritchie C², Lu J², Mulvaney P², Hollenberg LC^1,2,4

Show Affiliations

1. Centre for Quantum Computation and Communication Technology, The University of Melbourne , Melbourne Victoria 3010, Australia.
2. Bio21 Institute and School of Chemistry, The University of Melbourne , Melbourne Victoria 3010, Australia.
3. Département de Physique, Ecole Normale Supérieure de Cachan , 94235 Cachan, France.
4. School of Physics, The University of Melbourne , Melbourne Victoria 3010, Australia.

Abstract

Quantum sensors based on solid-state spins provide tremendous opportunities in a wide range of fields from basic physics and chemistry to biomedical imaging. However, integrating them into a scanning probe microscope to enable practical, nanoscale quantum imaging is a highly challenging task. Recently, the use of single spins in diamond in conjunction with atomic force microscopy techniques has allowed significant progress toward this goal, but generalization of this approach has so far been impeded by long acquisition times or by the absence of simultaneous topographic information. Here, we report on a scanning quantum probe microscope which solves both issues by employing a nanospin ensemble hosted in a nanodiamond. This approach provides up to an order of magnitude gain in acquisition time while preserving sub-100 nm spatial resolution both for the quantum sensor and topographic images. We demonstrate two applications of this microscope. We first image nanoscale clusters of maghemite particles through both spin resonance spectroscopy and spin relaxometry, under ambient conditions. Our images reveal fast magnetic field fluctuations in addition to a static component, indicating the presence of both superparamagnetic and ferromagnetic particles. We next demonstrate a new imaging modality where the nanospin ensemble is used as a thermometer. We use this technique to map the photo induced heating generated by laser irradiation of a single gold nanoparticle in a fluid environment. This work paves the way toward new applications of quantum probe microscopy such as thermal/magnetic imaging of operating microelectronic devices and magnetic detection of ion channels in cell membranes.

Go To Nano Lett

Soft Graphene Nanofibers Designed for the Acceleration of Nerve Growth and Development

Significance Statement

Understanding in the cells responses to programmed electrical signals is a vital tool for the study of the various biological research fields from bioelectronics to regenerative medicine, especially for the nerve engineering. In this study, a novel soft graphene nanofibers was successfully prepared by controlling the assembly of graphene oxide sheets on the surface of electrospun polymer nanofibers, and followed by chemical reduction with hydriodic acid. The graphene nanofibers have ultrathin graphene shells that wrapped the entire surface of the polymer nanofiber, which led to a flexible feature and recoverable electrical conductivity, and physicochemical stability in aqueous solutions with pH values from 2.0 to 11.0. By using the graphene nanofibers for cellular electrical stimulation, a sustained and irreversible change on the electron charge density and the location of the opened Ca²⁺ channel in the cell membrane was achieved, which avoided the common inhibitory effect of the long-term electrical stimulation on the replenishment of Ca²⁺ store, and resulted in a fast and sustainable promotion on the neurons growth and development. The speed of the neurites elongation and maturation of these neurons was almost two times than that of the neurons on the tissue culture plates and graphene film with or without electrical stimulation. We envision that the graphene nanofibers maybe can serve asa powerful tool for developing future therapies for nerve-related disease and injuries in central and peripheral nervous system. In addition, the successful formation of graphene shells in the complex 3D nanofibers extended the superior properties of graphene from traditional 2D nanometer scales to 3D micrometer scales by controlled assembly of graphene oxide sheets in 3D architectural geometry. We expect that this novel preparation technique will open a new way to adapt the graphene macroscopic real-world applications, not only to biomedicine, but also to chemical, electronic, energy, and environmental applications. 

 

About The Author

Zhang-Qi Feng completed a visiting scholarship at The University of Michigan in Ann Arbor as an exchange student (2008–2010), and then earned his Ph.D. (2010) degree in Biomedical Engineering from Southeast University. In fall 2010, he moved to Sun Yat-Sen University as a Lecturer supported by the “100 Talents Program” in the Department of Biomedical Engineering. Since spring 2014, he held an academic position in the School of Chemical Engineering of Nanjing University of Science & Technology. Feng developed several new micro/nano fibrous scaffolds by electrospinning, and has pioneered the application of electrospun fibers to bioartificial liver. His current research interests include the development of bio-inspired materials to improve tissue regeneration and works on advancing understanding the fundamental interaction between biomaterials and biological systems.

 

About The Author

Ting Wang completed a visiting scholarship at The University of Michigan in Ann Arbor as an exchange student (2008–2010), and then received her Ph.D. (2010) degree in Biomedical Engineering from Southeast University. In spring 2011, Ting got the position as a lecturer in the State Key Laboratory of Bioelectronics in the Southeast University. Ting current devotes her attention to developed several new micro/nanoparticles for drug delivery and its bio-safety, and understanding the fundamental interaction between nanoparticle and cell membrane.

 

About The Author

Jia-Cheng Li is currently carrying out master’s degree research with Prof. Zhang-Qi Feng at Nanjing University of Science & Technology. He received his Bachelor of Engineering in Pharmaceutical engineering from the University of Huang Shan, Anhui province, China in 2014. His research interests include the synthesis, properties, and applications of multiphase micro/nanoparticles.

 

About The Author

Bin Zhao is currently pursuing his master’s degree in Materials Science at Nanjing University of Science and Technology with Prof. Zhang-Qi Feng. He received a bachelor degree (2010) in Materials Chemistry from Binzhou University of China. His current research interests focus on creating short electrospun functional fibers for modulating the behavior of stem cells and on understanding the cell signal transduction in short fibers dispersions.

Journal Reference

Adv Mater. 2015 Nov;27(41):6462-8.

Feng ZQ¹, Wang T², Zhao B¹, Li J¹, Jin L³.

Show Affiliations

1. School of Chemical Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei, Nanjing, 210094, China.
2. State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210096, China.
3. School of Engineering, Sun Yat-Sen University, 51006, China.

Abstract

Soft graphene nanofibers with recoverable electrical conductivity and excellent physicochemical stability are prepared by a controlled assembly technique. By using the soft graphene nanofibers for cellular electrical stimulation, the common inhibitory effect of long-term electrical stimulation onnerve growth and development is avoided, which usually happens with traditional 2D conductive materials.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Impact of graphene oxide on viability of Chinese hamster ovary and mouse hepatoma MH-22A cells

Significance Statement

 Advances in nanoscience and nanotechnology, enabling the synthesis of new nanomaterials, have led to the development of a number of new drug delivery systems. Carbon materials, like graphene oxide (GO), are known to be more environmentally and biologically friendly than inorganic materials, and it is one of the most common elements in our ecosystem. In biomedical applications and nanomedicine, graphene oxide have been utilized over existing drug delivery vectors due to their ability to cross cell membranes easily and their high surface area, which provides multiple attachment sites for drug targeting. Indeed, with the expanding use of graphene oxide in biomedical applications, a broader understanding of its toxicology is of high importance. The molecular basis for translocation and toxicity of graphene oxide is still largely unclear. So, for the successful application of graphene oxide in nanomedicine the knowledge of the influence of graphene oxide on the viability of various cells and the search for the ways to reduce the toxicity of graphene oxide still remains an unsolved problem. In the present work we estimated the influence of graphene oxide and graphene oxide with 10% of bovine serum albumin on Chinese hamster ovary and mouse hepatoma MH-22A cells in vitro and the structural changes of the cells by atomic force microscopy (AFM), distribution of graphene oxide inside the cells by Raman spectroscopy, imaging. Healthy and cancer cells were chosen in order to determine if the impact of graphene oxide on cell viability is different in healthy and cancer cells.  

About The Author

Valentinas Snitka, Prof. dr. habil.

Valentinas Snitka internationally recognized expert in nanobiotechnology. He pioneered Scanning probe microscopy research in Lithuania in 1993; visiting researcher in Campinas University, Brasil, University of Pensilvania, USA, Twente University, The Netherlands, MIMOS Corporation, Kuala Lumpur etc.  His scientific expertise include Scanning Probe Microscopy methods and instrumentation, cell imaging and manipulation by SPM, electroporation of cells, nanoRaman (SERS,TERS) spectromicroscopy, synthesis and physicochemical characterization of nanoparticles, nanotoxicity, – 100+ publication in international journals, international patents, numerous invited lectures.  e was serving EC as FP6 Nanotechnology, Materials and Production committee member, a member of EU Scientific and Technical Research Committee (CREST). During 2007-2008 he was appointed as Chief Scientist at MIMOS Corp. Kuala Lumpur to develop nanotechnology roadmap and infrastructure. During last 3 years he is serving EC Directorate-General for Research, Directorate G: Industrial technologies as Project Technical Advisor for implementation of FP7 projects in Nanobiotechnologies. He participates in National SF project and is a leader of project funded by European Social Fund (2013-current). 

About The Author

Nora Grinceviciute, M.S.

Nora Grinceviciute completed a M.S. degree in the pharmaceutical sciences program from Lithuanian University of Life Sciences. Now she is Ph.D. student at Kaunas University of Technology (Research Center for Microsystems and Nanotechnology) in chemical engineering. She has experience in industrial biotechnology (2010-2012 Sicor Biotech UAB), working with atomic force microscopy, Raman spectroscopy, Supercritical angle fluorescence microscopy, chemical functionalization, lipid bilayer formation, studying impact of nanoparticles on cells and lipid membranes. Participated in research project as younger researcher, has an international collaboration experience working in University of Zurich (Switzerland). 

About The Author

Danute Batiuskaite, Assoc. Prof.  Dr.

Danute Batiuskaite received her PhD degree from Vytautas Magnus University, Kaunas, Lithuania, in 2003. Now she is an associate professor at the same university, the Faculty of Natural Science. She has the experience in teaching, participation in projects, national and international collaboration, doing experiments in vitro and in vivo, working with electropermeabilization of cells and tissues, searching for the optimal electrochemoterapy conditions, cytotoxicity of vitamins C and K3, impact of nanoparticles on cells. 

Figure legend.

a) Raman scattering image of GO distribution in CHO cell. Intensity maps of the ‘G’ band of GO nanoparticles. b) Viability of CHO and mouse hepatoma MH-22A cells after the treatment with BSA, GO and GO–BSA at different concentrations of GO. c) AFM image of CHO control cells.

 

 

Journal Reference

Toxicol In Vitro. 2015;29(5):1195-200.

Batiuskaite D¹, Grinceviciute N², Snitka V³.

Show Affiliations

1. Research Center for Microsystems and Nanotechnology, Kaunas University of Technology, 65 Studentu str., Kaunas LT-51369, Lithuania; Department of Biology, Faculty of Natural Sciences, Vytautas Magnus University, 58 K. Donelaicio str., Kaunas LT-44248, Lithuania.
2. Research Center for Microsystems and Nanotechnology, Kaunas University of Technology, 65 Studentu str., Kaunas LT-51369, Lithuania. Electronic address: nora.grinceviciute@ktu.lt.
3. Research Center for Microsystems and Nanotechnology, Kaunas University of Technology, 65 Studentu str., Kaunas LT-51369, Lithuania. Electronic address: vsnitka@ktu.lt.

Abstract

The evaluation of the cyto- and bio-compatibility is a critical step in the development of graphene oxide (GO) as a new promising material for in vivo biomedical applications. In this study, we report the impact of GO, with and without the addition of bovine serum albumin, on healthy (Chinese hamster ovary) and a cancer (mouse hepatoma MH-22A) cells viability and the estimation of the intracellular distribution of GO inside the cells in vitro. The viability tests were performed using a colony formation assay. The intracellular distribution of GO was estimated using Raman spectroscopy and imaging. The viability of both cell lines decreased with increasing concentration of  graphene  oxide (12.5-50.0 μg/ml): in the case of Chinese hamster ovary cells viability decreased from 44% to 11%, in the case of mouse hepatoma MH-22A cells–from 22% to 3%. These cell lines significantly differed in their response to GO and GO-BSA formulations. The results of viability tests correlate with results of atomic force microscopy and Raman spectroscopy and imaging findings. The GO influence on cell morphology changes, cell structure, cells colony growth dynamics and GO accumulation inside the cells was higher in the case of  mouse  hepatoma MH-22A cells.

Copyright © 2015 Elsevier Ltd. All rights reserved.

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Self-Guided Supramolecular Cargo-Loaded Nanomotors with Chemotactic Behavior towards Cells

Significance Statement

Tumor cells and wounded tissues produce an excessive amount of hydrogen peroxide. Drug delivery agents that could actively search and locate the diseased areas based on gradient of disease signal molecules between disease areas and blood stream/normal tissues would be an improvement to current targeting drug delivery systems. Although vesicular drug delivery systems such as polymersomes or liposomes are already used routinely in the clinic, the efficiency of targeted drug delivery is still limited mainly because these structures rely almost exclusively on passive accumulations a result of the leaky vasculature formed by rapid tissue growth found in tumors. Wilson approach is to use self-assembly as a tool to construct catalytic nanomotors that are able to carry cargo and direct their movement via chemotaxis. We are aiming to solve one of the most fundamental unresolved challenges in nanomotor research: “The Fantastic Voyage” – application of nanomotors for targeted drug delivery and diagnostics where nanomotors are able to actively seek and precisely locate tumour tissues by following a concentration gradient provided by the tumour signalling molecules.

Here we report a self-assembled nanomotor system able to self-propel and self-guide in a gradient of hydrogen peroxide produced by neutrophil cells. This is the first proof of concept experiment of nanosize motors able to carry a drug cargo and sense sick cells.  The nanomotor is formed through the assembly of smart amphiphilic block polymers into bowl shape structures incorporating an active catalyst in their inner compartment. Of nanometer scale, these motors are ideal for drug delivery in blood vessels/interstitial tissues and particularly attractive in biomedical applications. 

About The Author

Daniela A. Wilson (neé Apreutesei) received her B.Sc. degree (Hon) in chemistry from “A. I. Cuza” University of Iasi, Romania, in 2001 and an M.S. degree (Hon) in environmental chemistry from the same university in 2003. In 2006 she received her PhD with distinction “summa cum laudae” from “Gh. Asachi” Technical University of Iasi, Romania. During her PhD she obtained two fellowships in Japan and UK as exchange PhD student and Marie Curie fellow. She then worked as postdoctoral researcher at University of Pennsylvania, Philadelphia, USA and Radboud University Nijmegen, Netherlands in the groups of Prof. Virgil Percec and Prof. Roeland Nolte on several topics in synthetic organic chemistry, organometallic chemistry, and supramolecular and polymer chemistry. In 2012 she was awarded an ERC starting grant to investigate nanomotors with autonomous propulsion in biological systems. In 2015 she was awarded the first Athena Award from the Netherlands Organisation for Scientific Research for her excellent scientific research. She is currently assistant professor at the Institute for Molecules and Materials, Radboud University. Her research interests span a broad range of topics at the interface of supramolecular chemistry, macromolecular chemistry, and nanotechnology. 

Journal Reference

Angew Chem Int Ed Engl. 2015;54(40):11662-5.

Peng F¹, Tu Y¹, van Hest JC², Wilson DA³.

Show Affiliations

1. Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen (The Netherlands).
2. Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen (The Netherlands). j.vanhest@science.ru.nl.
3. Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen (The Netherlands). d.wilson@science.ru.nl.

Abstract

Delivery vehicles that are able to actively seek and precisely locate targeted tissues using concentration gradients of signaling molecules have hardly been explored. The directed movement toward specific cell types of cargo-loaded polymeric nanomotors along a hydrogen peroxide concentration gradient (chemotaxis) is reported. Through self-assembly, bowl-shaped poly(ethylene glycol)-b-polystyrene nanomotors, or stomatocytes, were formed with platinum nanoparticles entrapped in the cavity while a model drug was encapsulated in the inner compartment. Directional movement of the stomatocytes in the presence of a fuel gradient (chemotaxis) was first demonstrated in both static and dynamic systems using glass channels and a microfluidic flow. The highly efficient response of these motors was subsequently shown by their directional and autonomous movement towards hydrogen peroxide secreting neutrophil cells.

© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Independent effect of polymeric nanoparticle zeta potential /surface charge, on their cytotoxicity and affinity to cells

Significance Statement

Nanoparticles have shown great potentials in drug delivery, diagnosis and therapeutics. However, comprehensive understanding of the effect of nanoparticle zeta potential on its interaction with cells is still lack although such interaction has substantial impacts on nanoparticles efficacy. In this present work, we aim to investigate how nanoparticle zeta potential affects its cytotoxicity and disclose the underlying mechanisms by quantifying the interaction force between cells and nanoparticles via atom force microscopy (AFM). Four kinds of nanoparticles that possessed similar sizes around 230 nm and gradient zeta potentials ranging from -30 mv to +40 mv were fabricated. The cytotoxicity of these nanoparticles was found to be zeta potential-dependent. The nanoparticles  possessing positive surface charges were more toxic than negative nanoparticles, and the nanoparticles possessing higher like charges led to higher cytotoxicity. AFM showed that the positively charged nanoparticles or the nanoparticles with higher like charges had significantly higher interaction force to cells. The interaction force indicated the affinity to cells and could be the main reason of nanoparticles to induce cytotoxicity. This is the first report investigating the independent effect of nanoparticles zeta potential on its cytotoxicity and cellular affinity. Our findings suggest that in practical application, negative nanoparticles would be better for delivering general agents for diagnosis and therapy. On the other hand, positive nanoparticles would be better for delivering anti-tumor agents for chemotherapy. This work proposes a novel approach to investigate the cellular affinity of nanoparticles and demonstrates the importance of controlling zeta potential in practical use of nanoparticles.

About The Author

Yunfeng Lin, D.D.S., M.D., Ph.D., is Professor of State Key Laboratory of Oral Diseases, Sichuan University. He serves as the Vice-director of State Key Laboratory of Oral Diseases and Assistant Dean of West China School of Stomatology. He received his Ph.D. from Sichuan University in 2006. Dr. Lin’s research focus on adipose stem cells, biomaterials and craniofacial regeneration, such as bone, cartilage, tooth, fat et al. He has published over 100 papers, reviews and book chapters, and made several seminal contributions to the stem cells fields. He received Young scientific and technological innovation leader of China, Chinese Youth Science and Technology Award, Ministry of Education Science and Technology Progress Award, Henry Fok prize for young teachers in Colleges and Universities, New Century Excellent Talents of Chinese Ministry of Education and National Excellent Doctoral Dissertation of China.

About The Author

Dr. Peng received his PhD from Sichuan University (Chengdu, China) in 2012 and was appointed as a lecturer in Sichuan University in the same year and promoted as an associate professor in 2014. He studied in Keele University (Stoke-On-Trent, UK) as an exchange PhD student from 2010 to 2011 and researched in University of Copenhagen (Copenhagen, Denmark) as a visiting scholar in 2015. His research interests are biomaterials and drug delivery. He currently focuses on the interactions between nanoparticles and proteins/cells. He has received the Sichuan Provincial Award of Outstanding PhD Dissertation in 2013 and the First Prize of Chinese Outstanding Young Investigator Award (IADR-China Division) in 2014.  

Journal Reference

Cell Prolif. 2015 ;48(4):465-74. 

Shao XR¹, Wei XQ¹, Song X², Hao LY¹, Cai XX¹, Zhang ZR², Peng Q¹, Lin YF¹.

Show Affiliations

1. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
2. Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.

Abstract

OBJECTIVES:

Up to now, little research has been focussed on discovering how zeta potential independently affects polymeric nanoparticle (NP) cytotoxicity.

METHODS:

Polymeric nanoparticles of gradient zeta potential ranging from -30 mv to +40 mv were fabricated using the same poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx) biopolymer. Interaction forces between nanoparticles and cells were measured by atomic force microscopy (AFM). Cytotoxicity of the nanoparticles to cells was investigated by using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay.

RESULTS:

Four kinds of nanoparticle with similar sizes and gradient zeta potentials, were fabricated. Those with positive surface charges were found to be more toxic than those with negative surface charges. Positively charged nanoparticles or nanoparticles with higher ‘like’ charges, offered higher interaction force with cells.

CONCLUSION:

This work proposes a novel approach for investigating interaction between NPs and cells, and discloses the importance of controlling zeta potential in developing NPs-based formulations in the future.

© 2015 John Wiley & Sons Ltd.

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Coaxial nozzle-assisted 3D bioprinting with built-in microchannels for nutrients delivery

Significance Statement

Bioprinting is an exciting new technique that has been applied to the field of tissue engineering. Because cells require in vitro culturing prior to implantation, the fabricated 3D hydrogel structures must be adequately perfused to allow delivery of growth factors, oxygen, and other nutrients. Thus, the integration of a vascular network as occurs in thick tissues or organs is necessary and the most critical challenge in the successful application of bioprinting.

This study offers a novel 3D bioprinting method based on hollow calcium alginate filaments by using a coaxial nozzle, in which high strength cell-laden hydrogel 3D structures with built-in microchannels can be fabricated by controlling the crosslinking time to realize fusion of adjacent hollow filaments. With nutrition, cells are able to live longer, which allows easy fabrication of larger-scale organs with built-in microchannels as vascular network. This method can also be used in fabrication of hydrogel-based microfluidic devices, cell-based biosensor, and drug screening chips. 

About The Author

Yong He obtained his B.E. in engineering mechanics, at the China University of Mining and Technology in 2001. He obtained his Ph.D degree in mechanical engineering at the Zhejiang University in 2008. He is currently an associate professor at Zhejiang University, College of Mechanical Engineering. Also he is the deputy director of Key Lab of 3D Printing Process and Equipment of Zhejiang Province. His research is focused on the cell printing, development of organs on chips and microfluidic analytical devices. Now he has published above 30 papers and authorized above 30 patents. 

About The Author

Qing Gao receieved his B.E. in School of Mechanical and Automotive Engineering at Hefei University of Technology in 2012. He is currently a doctoral student in the College of Mechanical Engineering at Zhejiang University. His research focuses on bioprinting and biofabrication. 

About The Author

An Liu receieved his M.S. in School of Medicine at Wuhan University in 2013. He is currently a doctoral student in School of Medicine at Zhejiang University. His research focuses on bone defect repair and regeneration.  

About The Author

Dr Liang Ma received his Ph.D from mechanical engineering Department, University of Washington in Mar 2012. Then He jointed Zhejiang California NanoSystems Institute, Zhejiang University as research associate in Sep 2012. Currently Dr Liang focuses on the fabrication of novel tissue model systems with 3D cell printing. His researches including three aspects: In vitro glioblastoma multiforme (GBM) invasion model; 3D follicular model for in vitro maturation; 3D liver model for HBV infectious.   

 

Journal Reference

Biomaterials. 2015:203-15.

Gao Q¹, He Y², Fu JZ¹, Liu A³, Ma L⁴.

Show Affiliations

1. The State Key Lab of Fluid Power Transmission and Control, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China; Key Laboratory of3D Printing Process and Equipment of Zhejiang Province, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China.
2. The State Key Lab of Fluid Power Transmission and Control, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China; Key Laboratory of3D Printing Process and Equipment of Zhejiang Province, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: yongqin@zju.edu.cn.
3. Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
4. Zhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou 310058, China.

Abstract

This study offers a novel 3D bioprinting method based on hollow calcium alginate filaments by using a coaxial nozzle, in which high strength cell-laden hydrogel 3D structures with built-in microchannels can be fabricated by controlling the crosslinking time to realize fusion of adjacent hollow filaments. A 3D bioprinting system with a Z-shape platform was used to realize layer-by-layer fabrication of cell-laden hydrogel structures. Curving, straight, stretched or fractured filaments can be formed by changes to the filament extrusion speed or the platform movement speed. To print a 3D structure, we first adjusted the concentration and flow rate of the sodium alginate and calcium chloride solution in the crosslinking process to get partially crosslinked filaments. Next, a motorized XY stages with the coaxial nozzle attached was used to control adjacent hollow filament deposition in the precise location for fusion. Then the Z stage attached with a Z-shape platform moved down sequentially to print layers of structure. And the printing process always kept the top two layers fusing and the below layers solidifying. Finally, the Z stage moved down to keep the printed structure immersed in the CaCl2 solution for complete crosslinking. The mechanical properties of the resulting fused structures were investigated. High-strength structures can be formed using higher concentrations of sodium alginate solution with smaller distance between adjacent hollow filaments. In addition, cell viability of this method was investigated, and the findings show that the viability of L929 mouse fibroblasts in the hollow constructs was higher than that in alginate structures without built-in microchannels. Compared with other bioprinting methods, this study is an important technique to allow easy fabrication of lager-scale organs with built-in microchannels.

Copyright © 2015 Elsevier Ltd. All rights reserved.

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Dual-Enzyme-Loaded Multifunctional Hybrid Nanogel System for Pathological Responsive Ultrasound Imaging and T2-Weighted MRI

Significance Statement

As an emerging material, nanogel system is hydrogel nanoparticle, its ideal fluid-like transport properties and hydrophilic environment make the nanogel a perfect candidate for bio-catalysis, biomedical diagnosis and therapy. The immobilization (encapsulation) of enzymes within the gel matrix provides protection from structural alterations and subsequent deactivation of the enzymes, ensuring higher loadings and better substrate mobility for efficient catalysis. In addition, the unique hydrophilic environment and water-rich structure of this nanogel make it an ideal probe for magnetic resonance (MR) imaging, where the signal detected is directly related to relaxation time.

In this work, focused on exploiting the structure-function relationships of hydrogel, the dual-enzyme loaded multifunctional magnetic nanogel, which is composed of functionalized superparamagnetic iron oxide (SPIO) particles, a dual enzyme species (catalase and superoxide dismutase) and a polysaccharide cationic polymer glycol chitosan gel, was developed to be an efficient and safe probe for dual-modality pathological responsive ultrasound (US) and T₂-weighted MR imaging both in vitro and in vivo.

 

About The Author

Prof. Dr. Hui-Xiong Xu, MD, PhD is the Head and Professor of Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research and Education Institute, Tongji University School of Medicine (i.e. the First Affiliated Hospital), Shanghai, China. He is an Expert Panel Member of International Guideline of Contrast Enhanced Ultrasound in the Liver by World Federation of Ultrasound in Medicine and Biology (WFUMB), and a Member of International Contrast Ultrasound Society. His research interest includes US-guided ablation for tumor, Contrast-enhanced ultrasound, and US elastography.

_­­

About The Author

Dr. Qi-Gang Wang received his Ph.D. from Shanghai Institute of Ceramics, Chinese Academy of Sciences in 2005. From 2005 to 2011, he continued his research works in The Hong Kong University of Science and Technology, the University of Tokyo and Riken. He joined Tongji as a full professor and Young’s 1000 plan in 2011. His research interests will focus on 1) the mild radical polymerization for the preparation of nanocomposite gel, 2) the 3D printing and hierarchical pore design of functional gel, 3) the potential applications of functional gel in the interdisciplinary fields. He has published over thirty papers as first author and corresponding author including Nature.

About The Author

Dr. Xia Wang is an Assistant Professor of Chemistry department at Tongji University, China. Her research interests focus on the multifunctional nanogel composites and mesoporous silica-based nanomaterials for biomedical diagnosis and therapy.

Journal Reference

ACS Nano. 2015;9(6):5646-56.

Wang X¹, Niu D², Li P³, Wu Q¹, Bo X³, Liu B³, Bao S¹, Su T¹, Xu H³, Wang Q¹.

Show Affiliations

1. Department of Chemistry and Advanced Research Institute, Tongji University, Shanghai, 200092, China.
2. Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China.
3. Department of MedicalUltrasound, Shanghai Tenth People’s Hospital, Tenth People’s Hospital of Tongji University, Shanghai, 200072, China.

Abstract

A dual-enzyme-loaded multifunctional hybrid nanogel probe (SPIO@GCS/acryl/biotin-CAT/SOD-gel, or SGC) has been developed for dual-modality pathological  responsive  ultrasound (US) imaging and enhanced T2-weighted magnetic resonance (MR) imaging. This probe is composed of functionalized superparamagnetic iron oxide particles, a dual enzyme species (catalase and superoxide dismutase), and a polysaccharide cationic polymer glycol chitosan gel. The dual-modality US/MR imaging capabilities of the hybrid  nanogel  for  responsive US imaging and enhanced T2-weighted MR imaging have been evaluated both in vitro and in vivo. These results show that the hybrid nanogel SGC can exhibit efficient dual-enzyme biocatalysis with pathological species for responsive US imaging. SGC also demonstrates increased accumulation in acidic environments for enhanced T2-weighted MR imaging. Further research on these nanogel systems may lead to the development of more efficient US/MR contrast agents.

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Figure legend: Dual-Enzyme Loaded Hybrid Nanogel System for Pathological Responsive US and MR imaging.

 

 

Graphene-Based Platform for Infrared Near-Field Nanospectroscopy of Water and Biological Materials in an Aqueous Environment

Journal Reference

ACS Nano. 2015;9(8):7968-75.

Khatib O¹, Wood JD², McLeod AS, Goldflam MD, Wagner M, Damhorst GL, Koepke JC, Doidge GP, Rangarajan A, Bashir R, Pop E³, Lyding JW, Thiemens MH,Keilmann F⁴, Basov DN.

Show Affiliations

1. Department of Physics, Department of Chemistry, and JILA, University of Colorado , Boulder, Colorado 80309, United States.
2. Department of Materials Science and Engineering, Northwestern University , Evanston, Illinois 60208, United States.
3. Department of Electrical Engineering, Stanford University , Stanford, California 94305, United States.
4. Ludwig-Maximilians-Universität and Center for Nanoscience , 80539 München, Germany.

Abstract

Scattering scanning near-field optical microscopy (s-SNOM) has emerged as a powerful nanoscale spectroscopic tool capable of characterizing individual biomacromolecules and molecular materials. However, applications of scattering-based near-field techniques in the infrared (IR) to native biosystems still await a solution of how to implement the required aqueous environment. In this work, we demonstrate an IR-compatible liquid cell architecture that enables near-field imaging and nanospectroscopy by taking advantage of the unique properties of graphene. Large-area graphene acts as an impermeable monolayer barrier that allows for nano-IR inspection of underlying molecular materials in liquid. Here, we use s-SNOM to investigate the tobacco mosaic virus (TMV) in water underneath graphene. We resolve individual virus particles and register the amide I and II bands of TMV at ca. 1520 and 1660 cm(-1), respectively, using nanoscale Fourier transform infrared spectroscopy (nano-FTIR). We verify the presence ofwater in the graphene liquid cell by identifying a spectral feature associated with water absorption at 1610 cm(-1).

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