Search

Management of fungal biofilms represents a significant challenge to healthcare. As a preventive approach, minimizing adhesion between indwelling medical devices and microorganisms would be an important step forward. This study investigated the anti-fouling capacity of engineered nanoscale topographies to the pathogenic yeast Candida albicans . Highly ordered arrays of nano-pit topographies were shown to significantly reduce the physical adherence capacity of C. albicans . This study shows a potential of nanoscale patterns to inhibit and prevent pathogenic biofilm formation on biomedical substrates. [ABSTRACT FROM AUTHOR]

In culture isolated bone marrow mesenchymal stem cells (more precisely termed skeletal stem cells, SSCs) spontaneously differentiate into fibroblasts, preventing the growth of large numbers of multipotent SSCs for use in regenerative medicine. However, the mechanisms that regulate the expansion of SSCs, while maintaining multipotency and preventing fibroblastic differentiation are poorly understood. Major hurdles to understanding how the maintenance of SSCs is regulated are (a) SSCs isolated from bone marrow are heterogeneous populations with different proliferative characteristics and (b) a lack of tools to investigate SSC number expansion and multipotency. Here, a nanotopographical surface is used as a tool that permits SSC proliferation while maintaining multipotency. It is demonstrated that retention of SSC phenotype in culture requires adjustments to the cell cycle that are linked to changes in the activation of the mitogen activated protein kinases. This demonstrates that biomaterials can offer cross-SSC culture tools and that the biological processes that determine whether SSCs retain multipotency or differentiate into fibroblasts are subtle, in terms of biochemical control, but are profound in terms of determining cell fate. [ABSTRACT FROM AUTHOR]

Triboelectric nanogenerators (TENGs) are energy harvesters generating electricity via the triboelectric effect and electrostatic induction. However, the influence of interface mechanics on TENG performance requires attention. Here, we study the effect of random multiscale surface roughness on TENG performance using a novel in-situ optical technique to directly visualise the contact interface. To achieve this, a new type of TENG is developed based on transparent mica in contact with polyvinyl siloxane (PVS). A wide range of surface roughness instances were created on the PVS surface (Sq from 1.5 to 82.5 µm) by replicating 3D-printed masters developed from numerically generated rough surfaces. TENG output was found to be highly sensitive to surface roughness over a wide range of forces and frequencies. The dependence of real contact area on roughness was identified as the underlying cause. In this work, electrical output (and contact area) decreased significantly with increasing roughness. The highest output (smoothest PVS surface) gave open circuit voltage 222.8 V, short-circuit current density 53 mA/m2 and peak-power density 4256 mW/m2: a competitive output given the rapid and simple fabrication, low cost and long durability demonstrated. The new Mica-PVS TENG, the direct technique for TENG interface visualisation and the insights on the role of topography and contact area will be invaluable for future TENG design. [Display omitted] • New high-performance TENG based on PVS in contact with mica. • Competitive output (4256 mW/m2) despite cost effective and simple manufacture. • Optical technique for TENG interface visualisation & contact area measurement. • Comprehensive study on the effect of multiscale surface roughness on TENG output. • Output decreases with increasing roughness due to contact area reduction. [ABSTRACT FROM AUTHOR]

Custom engineered materials can influence the differentiation of human mesenchymal stem cells (MSCs) towards osteoblasts, chondrocytes and adipocytes, through the control of chemistry, stiffness and nanoscale topography. Here we demonstrate that polycaprolactone growth surfaces engineered with disordered (but controlled) 120 nm diameter dots (NSQ50), but not flat surfaces, promote osteogenic conversion of MSCs in the absence of other osteogenic stimuli. Differentiating MSCs on NSQ50 were found to express growth hormone receptors (GH) and stimulation with recombinant human GH (rhGH) further enhanced NSQ50-driven osteogenic conversion of MSCs. This increased osteogenesis coincided with an enhanced ability of GH to activate ERK MAP kinase on NSQ50, but not on flat topology. The importance of ERK for MSC differentiation was demonstrated by using the inhibitor of ERK activation, U0126, which completely suppressed osteogenesis of GH-stimulated MSCs on NSQ50. The ability of GH to activate ERK in MSCs may therefore be a central control mechanism underlying bone development and growth. [ABSTRACT FROM AUTHOR]

Abstract: Nanotopographical material modification represents a possible way of producing surfaces that influence cellular adhesion for biomaterials purposes. Here, two low-adhesion surfaces are studied with human genome microarrays (120nm diameter pits produced by electron beam lithography and 11nm high columns produced by colloidal lithography). In order to present the large numbers of results produced in a succinct and easy to understand manner, two types of recent bioinformatics methods were used; iterative group analysis and Ingenuity pathway analysis. These methods allowed the easy comparison of the nanomaterials and showed large-scale changes in areas of extracellular matrix, cell signalling and inflammation. The results demonstrate that whilst modes of cellular response to low-adhesion materials are similar, the more adhesion is reduced, the further ‘shut-down’ of critical cellular activities is observed. We also feel that the analysis used could be of interest to biomaterials scientists looking for easy ways to display microarray data efficiently. [Copyright &y& Elsevier]

In order for cells to react to topography, they must be able to sense shape. When considering nano-topography, these shapes are much smaller than the cell, but still strong responses to nano-topography have been seen. Filopodia, or microspikes, presented by cells at their leading edges are thought to be involved in gathering of special information. In order to investigate this, and to develop an understanding of what size of feature can be sensed by cells, morphological observation (electron and fluorescent microscopy) of fibroblasts reacting to nano-pits with 35, 75 and 120 nm diameters has been used in this study. The nano-pits are especially interesting because unlike many of the nanofeatures cited in the literature, they have no height for the cells to react to. The results showed that cell filopodia, and retraction fibres, interacted with all pit sizes, although direct interaction was hard to image on the 35 nm pits. This suggests that cells are extremely sensitive to their nanoevironment and that should be taken in to consideration when designing next-generation tissue engineering materials. We suggest that this may occur through nanocontact guidance as filopodia are moved over the pits. [Copyright &y& Elsevier]

Triboelectric nanogenerators (TENGs) have attracted significant interest as the alternative source of renewable energy. Their performance is believed to depend on the contact force, but its origin is yet to be established. Herein, we show that the origin lies in the real contact area A r , probed with novel experiments specifically designed for this purpose. The open circuit voltage V oc , short circuit current I sc and A r for a TENG, having two nominally flat tribo-contact surfaces, were found to increase with contact force/pressure. The A r is notably small at low pressures (0.25% at 16 kPa) that are typically experienced in wearable applications. However, it increases 328 fold to as much as 82% when it saturates beyond about 1.12 MPa pressure - achievable for impact with ocean waves. Critically, V oc and I sc saturate at the same contact pressure as A r suggesting that electrical output follows the evolution of the A r. Assuming that tribo-charges can only transfer across the interface at areas of real contact, it follows that an increasing A r with contact pressure should produce a corresponding increase in the electrical output. These results underline the importance of accounting for real contact area in TENG design to boost their performance, the distinction between real and nominal contact area in tribo-charge density definition, and the possibility of using TENGs as a self-powered pressure/load sensors. Crucially, the results indicate that the large contact pressures, readily available in applications such as road-tyre contact and wave energy, alone could be enough to boost the performance, thus avoiding the need for costly surface engineering to increase A r. [Display omitted] • Origin of the contact force-dependent performance of TENGs investigated. • Real contact area & electrical output measured over wide contact force range. • Origin is contact force-dependent real contact area owing to surface roughness. • Major implications for definition & measurement of tribocharge density. • Major implications in TENG design, pressure sensor design & high force applications. [ABSTRACT FROM AUTHOR]

Triboelectric nanogenerators (TENGs) allow generation of electricity based on charge transfer during repeated contact of suitably chosen surfaces. Recently, rapid advances have been made in boosting their performance, but advancement in fundamental understanding has progressed more slowly. Currently, the most popular TENG models assume idealized flat surfaces that guarantee complete contact and a contact force (or load)-independent response. However, all real surfaces possess some level of surface roughness which is known to produce a load-dependent contact area. We develop a new unified model (for dielectric-to-dielectric TENGs) which adds consideration of surface roughness to the established distance-dependent electric field model. We account for surface roughness by applying Persson's contact theory to determine the load-dependent contact area. The model is applicable from first touch to nearly complete contact provided deformation remains elastic. Compared to load-independent approaches, the presented model is a better predictor of TENG performance. It captures the load-dependent nature of TENG performance apparent in recent tests. It predicts that the electrical output can be expected to be tiny at low contact loads, but should converge to an upper-bound at higher loads as the contact area approaches complete contact. Comparison with test results reveal substantially better prediction of open circuit voltage V O C compared to load-independent models which tend to overestimate V O C considerably. By assisting the designers with better predictions of TENG output, the developed unified theory has huge potential for advancing the use of TENGs in applications such as wearables (i.e. low loads) to tidal or wave energy (i.e. large loads). Image 1 • New triboelectric nanogenerator model developed to account for surface roughness & the mechanics of rough surface contact. • Unifies the key contact mechanics and electrostatics of the problem. • Captures the contact-force dependent TENG electrical output apparent in experiments. • Electrical output tiny at low contact forces & converges to upper-bound at higher forces as contact area approaches complete contact. • Better predictor of TENG performance compared to force-independent models. Applicable from first touch to complete contact. [ABSTRACT FROM AUTHOR]

Micrometer and submicrometer size features were prepared in poly(methyl methacrylate) based polymer blends by hot-embossing using a customized silicon master. The surface patterns were design to contain particular functionalities for wetting in combination by the additive included in the polymer blend. More precisely copolymers containing MMA units and either a hydrophobic fluorinated monomer or a hydrophilic monomer was incorporated in the polymer mixture prior to embossing. Surface segregation using the appropriated annealing conditions allowed us to vary the interfacial chemical composition. Thus, we demonstrate that the wettability of the surface can be varied as a function of both the low surface energy additive and the annealing carried out whilst maintaining the overall surface topography. [ABSTRACT FROM AUTHOR]

Abstract: The use of cell sheets for tissue engineering applications has considerable advantages over single cell seeding techniques. So far, only thermoresponsive surfaces have been used to manufacture cell sheets without chemically disrupting the cell-surface interactions. Here, we present a new and facile technique to prepare sheets of epithelial cells using plasma polymerised acrylic acid films. The cell sheets are harvested by gentle agitation of the media without the need of any additional external stimulus. We demonstrate that the plasma polymer deposition conditions affect the viability and metabolic activity of the cells in the sheet and relate these effects to the different surface properties of the plasma polymerised acrylic acid films. Based on surface analysis data, a first attempt is made to explain the mechanism behind the cell sheet formation. The advantage of the epithelial cell sheets generated here over single cell suspensions to seed a PLGA scaffold is presented. The scaffold itself, prepared using a mould fabricated via photolithography, exhibits a unique architecture that mimics closely the dimensions of the native tissue (mouse intestine). [Copyright &y& Elsevier]

Abstract: The physiochemical characteristics of a material with in vivo applications are critical for the clinical success of the implant and regulate both cellular adhesion and differentiated cellular function. Topographical modification of an orthopaedic implant may be a viable method to guide tissue integration and has been shown in vitro to dramatically influence osteogenesis, inhibit bone resorption and regulate integrin mediated cell adhesion. Integrins function as force dependant mechanotransducers, acting via the actin cytoskeleton to translate tension applied at the tissue level to changes in cellular function via intricate signalling pathways. In particular the ERK/MAPK signalling cascade is a known regulator of osteospecific differentiation and function. Here we investigate the effects of nanoscale pits and grooves on focal adhesion formation in human osteoblasts (HOBs) and the ERK/MAPK signalling pathway in mesenchymal populations. Nanopit arrays disrupted adhesion formation and cellular spreading in HOBs and impaired osteospecific differentiation in skeletal stem cells. HOBs cultured on 10μm wide groove/ridge arrays formed significantly less focal adhesions than cells cultured on planar substrates and displayed negligible differentiation along the osteospecific lineage, undergoing up-regulations in the expression of adipospecific genes. Conversely, osteospecific function was correlated to increased integrin mediated adhesion formation and cellular spreading as noted in HOBS cultured on 100μm wide groove arrays. Here osteospecific differentiation and function was linked to focal adhesion growth and FAK mediated activation of the ERK/MAPK signalling pathway in mesenchymal populations. [Copyright &y& Elsevier]

For many bacteria, the ability to sense physical stimuli such as contact with a surface or a potential host cell is vital for survival and proliferation. This ability, and subsequent attachment, confers a wide range of benefits to bacteria and many species have evolved to take advantage of this. Despite the impressive diversity of bacterial pathogens and their virulence factors, mechanosensory mechanisms are often conserved. These include sensing impedance of flagellar rotation and resistance to type IV pili retraction. There are additional mechanisms that rely on the use of specific membrane-bound adhesins to sense either surface proximity or shear forces. This review aims to examine these mechanosensors, and how they are used by pathogenic bacteria to sense physical features in their environment. We will explore how these sensors generate and transmit signals which can trigger modulation of virulence-associated gene expression in some of the most common bacterial pathogens: Pseudomonas aeruginosa , Proteus mirabilis , Escherichia coli and Vibrio species. [ABSTRACT FROM AUTHOR]

This paper investigates why the static friction peak is mostly absent in reciprocating sliding and gross-slip fretting literature. Here, reciprocating sliding tests were conducted on ultra-smooth silicon surfaces. A prominent static friction peak was present in the initial cycles. However, a rapid wear-induced decay in the static friction peak occurred after the first cycle with the peak being mostly absent by about 30 cycles. Two possible explanations are proposed for the wear-induced decay: (1) that increasing surface roughness (with cycles) reduces the fully stuck contact area and (2) that wear reduces the bonding strength of the stuck interface by removing third body contaminant molecules. Predictions from a multi-asperity friction model are used to support these arguments. • Existence of the static friction peak in reciprocating sliding investigated. • Reciprocating sliding tests conducted on ultra-smooth silicon surfaces (Rq 0.32 nm). • Peak is present in initial cycles, but undergoes rapid wear-induced decay. • Multi-asperity friction model implemented for comparison with experiments. • Wear-induced decay explicable by either roughness changes or chemical changes. [ABSTRACT FROM AUTHOR]

The potential to optimise the performance of microstructured joints based on mechanically interlocking adherends is investigated via experimental testing and finite element (FE) analysis. The microstructured joints were realised via imprint lithography and injection moulding. FE modelling indicated that, a frictional interface (i.e. no adhesive) was sufficient to generate joint load capacities within about 7% of the experimental values. This result indicates that mechanical interlocking (via feature bending) accounts for most of the tangential load carrying capacity of the joints – opening up the possibility of adhesive-less joints. The FE model was then used for a design of experiments analysis to identify key relationships between interlocking geometric parameters and mechanical performance, with a three-way ANOVA analysis employed to determine relative importance. Feature aspect ratio was found to be the key parameter defining performance. Energy absorption increased with feature aspect ratio while load capacity peaked at an aspect ratio of 1 making square features the best compromise for load capacity and toughness. Finally, the viability of a more cost-effective, SLA-based 3D printing approach is demonstrated for fabricating the interlocking joints, whereby the potential to tailor for optimised hybrid performance was studied by varying feature geometry horizontally along the joint. [ABSTRACT FROM AUTHOR]

Abstract: Novel azido- and amino-functionalised fluorescent probes based on the BODIPY framework have been developed. The probes can be easily and cheaply synthesised, exhibit the highly desirable BODIPY fluorescent properties, and are amenable to ‘click’ and peptide chemistry methodologies. These probes provide a stable and readily available tool amenable for the visualisation of both solution and solid supported events. [Copyright &y& Elsevier]

Abstract: Topography and its effects on cell adhesion, morphology, growth and differentiation are well documented. Thus, current advances with the use of nanotopographies offer promising results in the field of regenerative medicine. Studies have also shown nanotopographies to have strong effects on stem cell self-renewal and differentiation. What is less clear however is what mechanotransductive mechanisms are employed by the cells to facilitate such changes. In fastidious cell types, it has been suggested that direct mechanotransduction producing morphological changes in the nucleus, nucleoskeleton and chromosomes themselves may be central to cell responses to topography. In this report we move these studies into human skeletal or mesenchymal stem cells and propose that direct (mechanical) signalling is important in the early stages of tuning stem cell fate to nanotopography. Using fluorescence in situ hybridization (FISH) and Affymetrix arrays we have evidence that nanotopography stimulates changes in nuclear organisation that can be linked to spatially regulated genes expression with a particular focus on phenotypical genes. For example, chromosome 1 was seen to display the largest numbers of gene deregulations and also a concomitant change in nuclear positioning in response to nanotopography. Plotting of deregulated genes in reference to band positioning showed that topographically related changes tend to happen towards the telomeric ends of the chromosomes, where bone related genes are generally clustered. Such an approach offers a better understanding of cell–surface interaction and, critically, provides new insights of how to control stem cell differentiation with future applications in areas including regenerative medicine. [Copyright &y& Elsevier]

Abstract: Research in to label free methods for biological analysis have brought interesting developments. Cell impedance spectroscopy has been one of the promising outcomes. Here we show the development of an 8-well impedance measurement setup and studied the use of conducting polymers as electrode material in cell impedance spectroscopy. We have developed devices using PEDOT:PSS electrodes and shown its advantages (lower impedance and faster to reach electrochemical equilibrium) over conventional materials, such as gold. It is observed through electrochemical analysis that the lower interfacial impedance is due to the low charge transfer resistance of PEDOT:PSS. MDCK cell proliferation experiments were performed using both types of electrode materials to provide a comparative result. We applied electrical modeling methods to understand the cell–substrate interactions and shown its applications in cell impedance spectroscopy. This study presents the development and advantages of cell impedance spectroscopy using conducting polymer electrodes. [Copyright &y& Elsevier]

Abstract: Open pores to maintain nutrient diffusion and waste removal after cell colonization are crucial for the successful application of constructs based on assembled membranes, in our case tubular scaffolds made of ɛ-polycaprolactone (PCL), for use in tissue engineering. Due to the complex three-dimensional structure and large size of such scaffolds needed for transplantable tissues, it is difficult to investigate the cell–pore interactions in situ. Therefore miniaturized bioreactors inside Petri dishes (30 mm in diameter), containing porous PCL or poly-dimethylsiloxane (PDMS) membranes, were developed to allow the interactions of different cells with defined pores to be investigated in situ during both static and perfusion cultures. Investigation of two different cell types (fibroblasts and cortical astrocytes) and how they interact with a range of pores (100–350 μm in diameter) for up to 50 days indicated that the cells either ‘covered’ or ‘bridged’ the pores. Three distinct behaviors were observed in the way cortical astrocytes interacted with pores, while fibroblasts were able to quickly bridge the pores based on consistent “joint efforts”. Our studies demonstrate that the distinct pore sealing behaviors of both cell types were influenced by pore size, initial cell density and culture period, but not by medium perfusion within the range of shear forces investigated. These findings form important basic data about the usability of pores within scaffolds that could inform the design and fabrication of suitable scaffolds for various applications in tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract: Topographic features can modulate cell behaviours such as proliferation, migration, differentiation and apoptosis. Biochemical mechanotransduction implies the conversion of mechanical forces (e.g. changes in cell spreading and morphology from changing surface topography) into biochemical signal via biomolecules. Still, little is known concerning which pathways may be directly involved in cell response to changes in the material surface. A number of pathways have been implicated using focused studies of ‘selected’ biomolecules rather than a global analysis of signal pathways. This study used a controlled disorder nanopit topography (NSQ50, fabricated by electron beam lithography) to direct osteoblast differentiation of progenitor cells. This topography is unique as it represents a middle route (from absolute order or random roughness) that allows osteoconversion with similar efficiency as dexamethasone and ascorbate treatment. Two direct-comparison proteomics techniques, firstly gel-based and then chromatography-based, were used to analyse progenitor proteome changes in response to the nanotopography. Many of the changed proteins form part of the Extracellular Signal-regulated Kinase (ERK1/2) pathway. [Copyright &y& Elsevier]

The potential to improve the mechanical properties of adhesive joints via micro-structured interlocking features is investigated. The micro-structured surfaces were fabricated in polycarbonate via injection moulding from a master template. The specimens were then bonded in an interlocking configuration to form single lap joints and tested to failure in tension. Planar untreated (i.e. un-abraded) and planar roughened (i.e. abraded) samples were also tested to provide benchmarks. Compared to the planar roughened case, results show that micro-structuring the interface can yield up to a 95.9% increase in strength and up to 162% increase in work to failure. Increases in strength and work to failure beyond the planar roughened level are attributed to mechanical interlocking of features. As deformation proceeds, progressive bending of each pair of interlocking features develops an increasing resistive load which allows the total load to significantly exceed that of the planar roughened case. Work to failure is increased via a combination of increased maximum force, increased displacement enabled by microfeature bending and a more torturous crack path. Low clearances between interlocking features were found to be favourable for mechanical properties owing to reduced bending stiffness of the repeating periodic unit at the interface. [ABSTRACT FROM AUTHOR]

The dry friction of surfaces with nanoscale roughness and the possibility of using micropatterning to tailor friction by manipulating contact area is investigated. Square wave patterns produced on samples from silicon wafers (and their unstructured equivalent) were slid against unstructured silicon counter surfaces. The width of the square wave features was adjusted to vary the apparent feature contact area. The existence of nanoscale roughness was sufficient to ensure Amontons' first law (F = μ P) on both structured & unstructured samples. Somewhat counterintuitively, friction was independent of the apparent feature contact area making it difficult to tailor friction via the feature contact area. This occurred because, even though the apparent feature contact area was adjusted, the surface roughness and nominal flatness at the contact interface was preserved ensuring that the real contact area and thereby the friction, were likewise preserved. This is an interesting special case, but not universally applicable: friction can indeed be adjusted by structuring provided the intervention leads to a change in real contact area (or interlocking)– and this depends on the specific surface geometry and topography. • Investigates dry friction of flat & structured surfaces with nanoscale roughness. • Studies micropatterning for tailoring of friction via manipulation of contact area. • Confirms validity of Amontons' first law for surfaces with nanoscale roughness. • Highlights special case with friction invariant of apparent feature contact area. • Tailoring friction via this approach requires changing the real contact area. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma is one of the most invasive and metastatic cancers and has a dismal 5-year survival rate. We show that N-WASP drives pancreatic cancer metastasis, with roles in both chemotaxis and matrix remodeling. lysophosphatidic acid, a signaling lipid abundant in blood and ascites fluid, is both a mitogen and chemoattractant for cancer cells. Pancreatic cancer cells break lysophosphatidic acid down as they respond to it, setting up a self-generated gradient driving tumor egress. N-WASP-depleted cells do not recognize lysophosphatidic acid gradients, leading to altered RhoA activation, decreased contractility and traction forces, and reduced metastasis. We describe a signaling loop whereby N-WASP and the endocytic adapter SNX18 promote lysophosphatidic acid-induced RhoA-mediated contractility and force generation by controlling lysophosphatidic acid receptor recycling and preventing degradation. This chemotactic loop drives collagen remodeling, tumor invasion, and metastasis and could be an important target against pancreatic cancer spread. • N-WASP is a crucial mediator of pancreatic ductal adenocarcinoma metastasis • Pancreatic cancer cells respond to self-generated gradients of LPA, driving tumor egress • N-WASP controls trafficking of LPAR1 receptor toward recycling versus degradation • N-WASP and LPAR1 trafficking control contractility, matrix remodeling, and invasion Pancreatic ductal adenocarcinoma is highly metastatic; recycling of the receptor LPAR1 drives metastasis in response to self-generated chemotactic gradients of LPA. Juin et al. show that the signaling adapter protein N-WASP coordinates recycling of LPAR1 back to the cell surface after internalization, driving efficient matrix remodeling, invasion, and tumor egress. [ABSTRACT FROM AUTHOR]