Friday, 30 May 2014

Mechanics in Biology and Medicine

Researchers from eleven different institutions have identified specific areas of biology and medicine in which mechanics could make significant contributions in a new Perspective article.  Three areas were analysed: nanoparticle-based drug delivery, medical devices, and cell mechanics.

Nanoparticle –based drug delivery is one area ripe with opportunitiy.  In particular, modelling of the drug delivery process would reduce the need for physical experiments and expedite nanoparticle design for improved delivery.  Integrating computational modelling into the rational design of nanoparticles offers the opportunity to improve nanoparticle performance during, for example, vascular transport and endocytosis. 

Modeling also has a role to play in improving a variety of medical devices.  For example, recent developments in “organ-on-chip” devices require understanding of complex transport behaviours through channels, gels and complex tissues.  In another area, advances in ventricular assist devices could greatly benefit from computational mechanics simulations to optimise design and hopefully mitigate problems such as thrombus formation. 

Finally, in the section entitled “cell mechanics”, the authors identified a critical need for better constitutive models for single-cell mechanical behaviour, taking into account the active behaviour of cells.  The mechanics community could also contribute to the development of integrated tools for single cell studies exploring biological variability.

This is just a brief summary of issues that particularly resonated with me.  If you’re interested in the topic, I recommend you go to the full article. This is a long paper, and so my “Bites” length rules are waived for this one.  

USNCTAM perspectives on mechanics in medicine; G. Bao et al, J. R. Soc. Interface 2014 11, 20140301

Thursday, 29 May 2014

Fishing for rare cells in blood samples

A multi-stage microfluidic device separated tumour or leukaemic cells spiked into blood with high efficiency.  A filtration stage removed cell aggregates and debris.  Then a carefully designed microfluidic channel generated hydrodynamic forces which focussed the larger cancer cells into the channel centre; smaller blood cells were separated off.  The central fluid component entered a third steric hindrance region which further purified the rare cells by their size and mechanical properties. 

High-throughput rare cell separation from blood samples using steric hindrance and inertial microfluidics; S. Chen et al, Lab on a Chip; DOI: 10.1039/c3lc51384j

Wednesday, 28 May 2014

Cotton-wool-like sol-gel glass from electrospinning

Researchers have combined sol-gel processing with electrospinning to produce cotton-wool-like CaO-SiO2 glass structures.  The cotton-wool-like morphology was attributed to the rheological properties of the electrospinning solution causing branching of the primary jet and to fibre regions rich in calcium ions creating bending instabilites in the applied electric field.  The material was moldable and could be packed into complex bone defects.  Preliminary results suggested the materials were bioactive and non-cytotoxic.

Cotton-wool-like bioactive glasses for bone regeneration; G. Poologasundarampillai et al; Acta Biomaterialia;

An open access paper

Tuesday, 27 May 2014

Symmetric protein nanomaterials from novel co-assembling protein subunits

A run of protein-based materials papers (excluding yesterday’s dialysis paper).  Apologies for this – I do try to be diverse in content.  But this one is from my own journal Nature so I couldn’t resist.  Here it is.

Researchers have described the precise self-assembly of protein nanomaterials from two novel co-assembling protein subunits.  Computational methods were used to predict amino acid sequences (one for each subunit) which would stabilize the interfaces between the folded subunits and drive assembly of multiple copies into a specific symmetric architecture.  The researchers experimentally verified the computational methods by fabricating five different two-component co-asssembled nanomaterials each forming one of two targeted tetrahedral architectures.

Accurate design of co-assembling multi-component protein nanomaterials; N.P. King et al; Nature AOP; doi:10.1038/nature13404

Monday, 26 May 2014

A miniaturised kidney dialysis machine for newborn babies

A miniaturised kidney dialysis machine with fluid control capability for newborn babies has been developed.  The dialyzer operates with a much lower volume of blood and very low blood and ultrafiltration flows.  The device allows the use of a small catheter preventing damage to a baby’s blood vessels.  It has been successfully tested on a critically ill newborn baby.  The patient was discharged from intensive care after 39 days.

Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM); C. Ronco et al, The Lancet, Volume 383, Issue 9931, Pages 1807 - 1813, 24th May 2014

P.S. learn more about this technology and enjoy a "Cappucino with Claudio Ronco", the lead author of the paper in The Lancet, on Youtube

Sunday, 25 May 2014

Concerted folding and networking of short peptides

Short peptide sequences have been concomitantly folded into a specific helical conformation and networked into a single crystal co-ordination material by silver(I) co-ordination.  The new material contained two types of chiral nanochannel.  The larger of the nanochannels, with a diameter of around 2nm, offered a high degree of both chiral recognition and biomolecular recognition.  BF4- counterions in the crystalline network could be exchanged with other anions in a single-crystal-to-single-crystal transformation.

Coordination-Driven Folding and Assembly of a Short Peptide into a Protein-like Two-Nanometer-Sized Channel; T. Sawada et al, Angewandte Chemie International Edition, DOI: 10.1002/anie.201403506

Saturday, 24 May 2014

Artificial biocomposites of silk fibroin and amyloid fibrils

Researchers have combined two widely-studied fibrous protein assemblies – silk fibroin fibrils and amyloid fibrils – into a novel composite material. By varying the weight ratio of the two components, mechanical properties could be tuned: more amyloid fibril increased tensile modulus whereas more silk fibroin promotes tougher composites. The amyloid component could be enzymatically removed to generate a porous silk membrane.  Inorganic components were also added and a shape memory effect observed.  

Modulating Materials by Orthogonally Oriented β-Strands: Composites of Amyloid and Silk Fibroin Fibrils; S. Ling et al; Advanced Materials; DOI: 10.1002/adma.201400730


Bioengineering Bites is one month old.  Here are a few stats.  Twenty five papers from eighteen different journals were highlighted.  Readers from at least twenty different countries visited the site. 

The readers choice for the month – the Bites with the most hits – were

1. Vascularised hydrogels (10/05/14)
2. Lab-on-a-chip based blood plasma separation (30/04/14)
3. Bone marrow on a chip (05/05/14)

Take a look if you’ve not read them.

Many of you will have noticed that I increased the word limit of each Bite to 70 words to make life a little easier for me.  I have also increased the maximum age that a paper can be for coverage by a few days.  This is to minimise moments of bashing my head against a wall when I missed a paper I would have liked to highlight.

I’ve received lots of positive feedback on the site.  I hope all readers find Bioengineering Bites interesting and/or useful.  I look forward to month two!

Thursday, 22 May 2014

A shear stress threshold for angiogenesis

In vitro experiments using microfabricated microfluidic devices have revealed a threshold of shear stress from fluid flow above which endothelial cell monolayers sprout new blood vessels.  The shear stress also sustained the sprout and prevented vessel retraction.  Further experiments revealed that matrix metalloproteinase 1 expression increased dramatically at the shear threshold.  These findings offer a basic mechanism for regulating vessel densities in tissue modulated by other mechanical, geometric,and biochemical factors.

Fluid shear stress threshold regulates angiogenic sprouting; P.A.Galie et al; PNAS; doi:10.1073/pnas.1310842111

Wednesday, 21 May 2014

Self-powered sensor for human-machine interfacing

Researchers have created a thin-film triboelectric sensor which uses a polymer-nanowire-decorated triboelectric-negative polymer surface to achieve ultrasensitive tactile sensing. The device harnessed the triboelectric charges generated in the polymer surface upon contact with a foreign object to generate an output voltage.  The sensor retained its functionality even when applied to a curved surface.  Demonstrated applications included various alarm systems powered by touch alone.  Approach also offers possibilities for electronic-skin-type technologies. 

Self-Powered, Ultrasensitive, Flexible Tactile Sensors Based on Contact Electrification; G. Zhu et al, Nano Letters;

Tuesday, 20 May 2014

Graphene / MoS2 heterostructures for DNA detection

Researchers have fabricated a graphene/MoS2 heterostructure for label-free selective detection of DNA hybridization. The graphene protected the MoS2 from ambient moisture and oxygen and acted as a biocompatible host for the DNA molecules.  The photoluminescence intensity from the MoS2 layer increased with increased concentration of target DNA. The differentiation of complementary and one-base mismatched DNA with the graphene/MoS2 heterostructure could be performed at a concentration as low as 1 attomole.

Graphene/MoS2 Heterostructures for Ultrasensitive Detection of DNA Hybridisation; P.T.K. Loan et al, Advanced Materials; DOI: 10.1002/adma.201401084

Monday, 19 May 2014

The future of polymer therapeutics

Ruth Duncan offers her perspective of the challenges and opportunities for the polymer therapeutics community.  She discusses recent clinical successes and failures and offers valuable suggestions which could improve translation of products from the lab to the clinic.  Key considerations include (amongst others) appropriate selection of polymer and drug for a specific application, sufficient materials characterization (not just biological analysis), clinically relevant preclinical models and improved clinical trial design.

Polymer therapeutics: Top 10 selling pharmaceuticals What next?, R.Duncan, Journal of Controlled Release,

Sunday, 18 May 2014

All the right journals?

Am I looking at all the right journals?  Let me know which are your favourite journals to publish in and to read.  If it’s not already on my list of journals to search, it’ll go on!  Let me know by commenting to this post or emailing me at bioengineeringbites#yahoodotcom.  I look forward to hearing from you!

Saturday, 17 May 2014

Manipulating cells on magnetic circuit boards

A circuit board of magnetic pathways has enable precise manipulation of magnetic particles and magnetic-nanoparticle-labeled cells in fluidic environments upon application of a rotating magnetic field.  The trajectory of particles was programmable with conducting lines integrated into the circuit board which allowed transportation of particles from one pathway to another. The device had a multiplexed design to facilitate massively parallel single cell operations such as cell sorting, experimentation and retrieval. 

Magnetophoretic circuits for digital control of single particles and cells; B. Lim et al, Nature Communications; DOI: 10.1038/ncomms4846

Friday, 16 May 2014

Antibiotic AuPt nanoparticles

Researchers have discovered that bimetallic nanoparticles containing gold and platinum act as antimicrobial agents and are effective against a range of bacteria including E.coli, Salmonella Choleraesius and Pseudomonas Aeruginosa.  Pure gold or pure platinum nanoparticles were not antibiotic at all.  Investigations suggested two mechanisms in operation: disruption of the cell membranes and increased intracellular ATP.  The nanoparticles were not toxic to mammalian cells in vitro

Tuning the Composition of AuPt Bimetallic Nanoparticles for Antibacterial Applications, Y. Zhao et al, Angewandte Chemie International Edition, DOI: 10.1002/anie.201401035

Thursday, 15 May 2014

Enhancing photodynamic therapy using biomolecules

Researchers have demonstrated that the upconversion of near-infra-red laser light to visible or ultra-violet by interactions with biomolecules in-situ makes photodynamic therapy more effective.  A known photosensitizer was activated by both near-infra-red light and the upconverted radiation generated by nonlinear optical processes operating in either lipid molecules or collagen.  The approach substantially increased the efficiency with which the photosensitizer destroyed cells in vitro compared to two-photon absorption by near-infra-red alone. 

Photodynamic therapy by in situ nonlinear photon conversion, A. V. Kachynski et al, Nature Photonics AOP, DOI: 10.1038/NPHOTON.2014.90

Tuesday, 13 May 2014

Delivering siRNAs to endothelial cells

Scientists have synthesised nanoparticles which efficiently delivered siRNAs to endothelial cells in vivo and facilitated silencing of up to five different endothelial genes concurrently.  Gene expression in several other cell types was not significantly affected by the presence of the delivery agent.  The nanoparticles, made of low-molecular-weight polyamines and lipids, reduced target gene expression in multiple animal models.  In lung cancer models, primary tumour growth and metastases were both reduced. 

In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight; J.E. Dahlman et al, Nature Nanotechnology, DOI: 10.1038/NNANO.2014.84.

Monday, 12 May 2014

Polymer synthesis at microbial surfaces

A redox system operating in bacteria produces copper species which can catalyse an ATRP-type polymerization at the bacterial surface, researchers have shown.  The resulting macromolecules selectively bound to the microbial strain which templated them.  The approach was also used to label polymer side chains in-situ.  Potential applications include diagnostics.

Bacteria-instructed synthesis of polymers for self-selective microbial binding and labelling; E.P. Magennis et al, Nature Materials AOP; DOI: 10.1038/NMAT3949

Sunday, 11 May 2014

Mechanics of lipid membranes

Researchers describe a method for investigating the viscosity of lipid membranes.  Tracers consisting of two microspheres coupled to a specific lipid allowed measurements of translational and rotational diffusion co-efficient and thus viscosity.  The method showed that adding vesicle trafficking protein Sar1p to membranes resulted in dramatic increase in membrane viscosity.

Measuring Lipid Membrane Viscosity Using Rotational and Translational Probe Diffusion; T.T. Hormel et al; Physical Review Letters; 112, 188101 (2014)

Saturday, 10 May 2014

Vascularised hydrogels

Researchers have created networks of microchannels in a variety of hydrogels using a micromolding strategy.   Networks of channels enhanced osteogenic cell viability and differentiation in cell-laden micromolded gels.  The channels could be lined with a confluent layer of endothelial cells to create an engineered vasculature.  The hydrogels remained fully perfused. 

Hydrogel Bioprinted Microchannel Networks for Vascularization of Tissue Engineering Constructs; L.E.Bertassoni et al, Lab on a Chip, DOI: 10.1039/C4LC00030G

Friday, 9 May 2014

How cells change nanoparticles

The protein corona surrounding nanoparticles exposed to biological cells changes according to nanoparticle characteristics, cell type and length of exposure, studies show.  These changes alter nanoparticle aggregation, cell membrane affinity, uptake and retention.  Results suggest nanoparticles have an ever-changing biological ‘identity’ as they travel through numerous microenvironments in the body.

Secreted Biomolecules Alter the Biological Identity and Cellular Interactions of Nanoparticles; A. Albanese et al; ACS Nano; DOI: 10.1021/nn4061012 

Wednesday, 7 May 2014

Non-invasive monitoring of fetal development

Researchers probed the temporal dynamics of gene transcription in the cell-free RNA of pregnant women’s blood plasma.  Microarray techniques and next-generation sequencing data identified and quantified transcripts from specific fetal tissues and placenta.  Findings suggest a route to diagnosing pregnancy complications and fetal abnormalities.  Methods might also identify neurodegenerative disorders.

Noninvasive in vivo monitoring of tissue-specific global gene expression in humans; W. Koh et al; PNAS; doi: 10.1073/pnas.1405528111

Tuesday, 6 May 2014

Bone marrow on a chip

Bone marrow grown within a device implanted in a mouse resembles natural marrow, researchers reported.  The tissue could be explanted whole, inserted into a lab-on-a-chip and maintained in vitro for 7 days.  The cultured marrow mimicked tissue responses to radiation toxicity and treatment for exposure normally only observed in vivo.

Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro; Y-S Torisawa et al; Nature Methods AOP doi:10.1038/nmeth.2938

Monday, 5 May 2014

Inflammation-induced drug release

Researchers proposed and tested in vivo pH-responsive microspheres with PLGA-shells and NaHCO3 / antibiotic cores for the treatment of osteomyelitis.  The acid from infected bone tissue reacted with NaHCO3 to generate CO2 which disrupted the PLGA shells and released the antibiotic.  Microspheres were delivered via an injectable calcium phosphate cement.

Inflammation-induced drug release by using a pH responsive
gas-generating hollow-microsphere system for the treatment of osteomyelitis; M.F. Chung et al; Advanced Healthcare Materials; DOI: 10.1002/adhm.201400158.

Sunday, 4 May 2014

Micro-RNA sensor for cancer diagnostics

Micro-RNA-21 is overexpressed in many cancers.  A new magnetobiosensor selectively detected micro-RNA-21 at low concentrations in cancer cells and tissue samples. RNA plant-virus proteins tethered to magnetic beads captured DNA duplexes formed by adding anti-Micro-RNA-21 to the Micro-RNA-21-containing samples.  Beads were captured on screen-printed electrodes for electrochemical detection of microRNA. 

Magnetobiosensors based on viral protein p19 for micro-RNA
determination in cancer cells and tissues; S. Campuzano et al; Angewandte Chemie International Edition, DOI: 10.1002/anie.201403270 

Friday, 2 May 2014

Mechanically functional engineered cartilage

Researchers have mimicked mesenchymal condensation using a cellular self-assembly method to successfully generate centimetre-sized anatomically-shaped cartilage from human mesenchymal stem cells.  The engineered tissue was stratified with physiologically relevant values of Young’s modulus and co-efficient of friction.  In vitro data suggested the method could be used to repair cartilage defects.

Large, stratified and mechanically functional human cartilage grown in vitro by mesenchymal condensation, S. Bhumiritana et al, PNAS, doi/10.1073/pnas.1324050111

Thursday, 1 May 2014

Simulating neural networks

A fast and energy efficient circuit board which models neural circuits in the human brain offers new opportunities for robotics and brain-machine interfaces.  The device contains 16 chips and consumes just three watts to simulate in real time the computing capability of a million neurons with billions of synaptic connections.

Neurogrid: A mixed-analog-digital multichip system for large-scale neural simulations; B.V.Benjamin et al; Proceedings of the IEEE; DOI 10.1109/JPROC.2014.2313565; 2014.