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Considerable improvements have been obtained in physical and mechanical properties of free standing liquid crystal graphene oxide (LCGO) films in their hydrated state, by modification of LCGO dispersions with a low quantity of chloride salts. Addition of salts to LCGO dispersions result in an increase of the storage and loss moduli and viscosity through the interaction between cations and functional groups of LCGO, with the magnitude of increase being dependent upon the concentration of the salt added. A viscosity increase of between 30× and 300× (depending on the salt type) is recorded when salt is added at a concentration as low as 80 mM while storage and loss moduli increase up to 23× and 29×, respectively. Free standing films made from the salt treated LCGO dispersions contained up to 26% water in their structure and were observed to have significantly improved mechanical (2× to 5× increase) and electrical properties (decreased surface resistance up to approximately 670×) compared to free standing films prepared without chloride salts. The influence of the salts on properties of LCGO dispersions and their hydrated free standing films is postulated as a complex interplay of many factors such as the size of cations, the valency of positive charge of the cations, ratio of charge and cations size, as well as the hygroscopic nature of the salts.

Controlled release is at the forefront of modern bioscience as it aims to address challenges associated with the dosing of drugs within required levels for therapeutic effect. Many materials and approaches can be used to control the release from different reservoirs including nanoparticles, liposomes and hydrogels. Using thermoresponsive hydrogels, near infrared illumination of plasmonic nanoparticles can be used to control the hydrogel through localised surface plasmon resonance heating. This work extends beyond a material level and pursues detailed examination of the drug release characteristics of a variable acrylic acid poly(N-isopropylacrylamide) coated gold nanorod system using dexamethasone as a model drug. Release was examined under different irradiation power densities and exposure times. Bulk heating effects in all stimulation protocols did not exceed the lower critical solution temperature of the system, but a marked increase in release was seen following stimulation. This was likely due to more intense heating occurring around the nanorods. A release model was established to describe the amount of drug eluted relative to input energy, suggesting that shorter irradiation periods release the drug more efficiently. The data reported establishes plasmonically modulated thermosensitive hydrogels as a candidate material that can be tailored to specific clinical applications of stimulated release.

Engineering of 3D regenerative skeletal muscle tissue constructs (skMTCs) using hydrogels containing muscle precursor cells (MPCs) is of potential benefit for repairing Volumetric Muscle Loss (VML) arising from trauma (e.g., road/industrial accident, war injury) or for restoration of functional muscle mass in disease (e.g., Muscular Dystrophy, muscle atrophy). Additive Biofabrication (AdBiofab) technologies make possible fabrication of 3D regenerative skMTCs that can be tailored to specific delivery requirements of VML or functional muscle restoration. Whilst 3D printing is useful for printing constructs of many tissue types, the necessity of a balanced compromise between cell type, required construct size and material/fabrication process cyto-compatibility can make the choice of 3D printing a secondary alternative to other biofabrication methods such as wet-spinning. Alternatively, wet-spinning is more amenable to formation of fibers rather than (small) layered 3D-Printed constructs. This study describes the fabrication of biosynthetic alginate fibers containing MPCs and their use for delivery of dystrophin-expressing cells to dystrophic muscle in the mdx mouse model of Duchenne Muscular Dystrophy (DMD) compared to poly(DL-lactic-co-glycolic acid) copolymer (PLA:PLGA) topically-seeded with myoblasts. In addition, this study introduces a novel method by which to create 3D layered wet-spun alginate skMTCs for bulk mass delivery of MPCs to VML lesions. As such, this work introduces the concept of “Trojan Horse” Fiber MTCs (TH-fMTCs) and 3d Mesh-MTCs (TH-mMTCs) for delivery of regenerative MPCs to diseased and damaged muscle, respectively.

Fibrinolytic drugs have been successfully used to manage acute thrombotic and thromboembolic conditions. However, their narrow administration time window, rapid clearance, and possible inactivation limit their efficient and wider application. Most importantly, they present a substantial risk of fatal bleeding complications, which are a major cause of mortality and morbidity. Improving the therapeutic outcomes of pharmacological thrombolysis, including alleviating associated side effects, is an urgent challenge. In this context, nano-drug delivery systems have attracted major interest. State-of-the-art nanodelivery systems have achieved reduced immunogenicity and a significant prolongation of the biological half-life of drugs, the latter allowing their application as boli instead of infusions. Recent research focuses on theranostic systems capable of image-guided thrombolysis, clot targeting strategies, and stimuli-responsive systems. The latter are designed so that an external or internal stimulus triggers the drug release, offering unique spatiotemporal control over the treatment and potentially minimizing side effects. In this review, the authors discuss the different nanodelivery platforms and focus on stimuli-responsive systems, highlighting their therapeutic advantages and the challenges for their clinical translation.

Delivery of small dosages of anti-epileptic drug (AED) directly into the brain from implantable degradable polymers has been reported to alleviate epilepsy activity in a GAERS animal model, however this system delivers a continuous dose of AED to the brain. We describe here the development of an active drug delivery system whereby AED delivery is initiated by the onset of an epileptic event and controlled by a custom hardware device. The system is comprised of an electrocortigographic (ECoG) data receiver, computational hardware, and a drug delivery component. The system initiates the release of an AED from an electrically conductive polymer when a seizure biomarker is detected above a pre-set threshold. Evaluation of the system showed that it is possible to vary the quantity of drug released linearly by varing the amount of charge injected into the drug loaded electroactive polymer. In addition it is possible to induce drug release within 10 s of injecting the charge, highlighting the responsive nature of the system. This work demonstrates a significant advance in the development of a device that combines the electronics capable of monitoring ECoG activity, detecting epileptic seizures and initiating drug delivery.

Mg alloys are attractive materials for medical devices. The main limitation is that they are prone to corrosion. A low toxicity surface coating that enables uniform, controlled corrosion at a desired rate (this usually means it must offer barrier functions for a limited time period) is desirable. Phosphate-based ionic liquids (ILs) are known to induce a coating that can reduce the corrosion rate of Mg alloys, Furthermore, some ILs are known to be biocompatible and therefore, controlling the corrosion behaviour of an Mg alloy and its surface biocompatibility can be achieved through adding an appropriate low toxic IL surface layer to the substrate. In this study, we have evaluated the cytotoxicity of three phosphate-based ILs to primary human coronary artery endothelial cells. Among them, tributyl(methyl)-phosphonium diphenylphosphate (P1,4,4,4dpp) shows the lowest cytotoxicity. Therefore, further work was aimed at developing an appropriate treatment method to produce a homogeneous and passive surface coating based on P1,4,4,4dpp IL, with the focus on investigating the effect of treatment time. The results showed that that the formation of IL coating on AZ31 has proceeded progressively, and treatment time plays an important role. An IL treatment at 100 °C with an extended treatment time of 5 h significantly enhanced corrosion resistance of the AZ31 alloy in simulated body fluid. Additionally, the corrosion morphology was uniform and there was no evidence of “localized pitting corrosion” observed. Such a performance makes this ionic liquid coating as a potential surface coating biodegradable Mg-based implants.

The development of electrically conducting fibers based on known cytocompatible materials is of interest to those engaged in tissue regeneration using electrical stimulation. Herein, it is demonstrated that with the aid of rheological insights, optimized formulations of graphene containing spinnable poly(lactic-co-glycolic acid) (PLGA) dopes can be made possible. This helps extend the general understanding of the mechanics involved in order to deliberately translate the intrinsic superior electrical and mechanical properties of solution-processed graphene into the design process and practical fiber architectural engineering. The as-produced fibers are found to exhibit excellent electrical conductivity and electrochemical performance, good mechanical properties, and cellular affinity. At the highest loading of graphene (24.3 wt%), the conductivity of as-prepared fibers is as high as 150 S m-1 (more than two orders of magnitude higher than the highest conductivity achieved for any type of nanocarbon-PLGA composite fibers) reported previously. Moreover, the Young's modulus and tensile strength of the base fiber are enhanced 647- and 59-folds, respectively, through addition of graphene.

Biodegradable fibers for the controlled delivery of anti-inflammatory agent dexamethasone were developed and studied. Mono and core–shell structure fiber are prepared by wet-spinning solutions of hydrophobic poly (lactide-co-glycolide) and hydrophilic alginic acid shell. The two model drugs, dexamethasone and dexamethasone-21-phosphate, were entrapped in core and shell, respectively. These fibers were characterized in terms of morphology, diameters, mechanical properties, in vitro degradation, and drug release. The optical microscopy and scanning electron microscopy photos revealed directly that fibers possessed core–shell structure. The release of dexamethasone and dexamethasone-21-phosphate was investigated, and the results showed that alginate shell retarded dexamethasone release significantly in both early and late stages. The core–shell structure fiber release shows a two stage release of dexamethasone and dexamethasone-21-phosphate with distinctly different release rates, and minimal initial burst release is observed. The results indicated that the prepared fibers are efficient carrier for both types of dexamethasone. Copyright © 2016 John Wiley & Sons, Ltd.

The demands of multifunctional scaffolds have exceeded the passive biocompatible properties previously considered sufficient for tissue engineering. Herein, a novel and facile method used to fabricate a core-shell structure consisting of a conducting fiber core and an electrospun fiber shell is presented. This multifunctional structure simultaneously provides the high conductivity of conducting polymers as well as the enhanced interactions between cells and the sub-micron topographical environments provided by highly aligned cytocompatible electrospun fibers. Unlimited lengths of PEDOT:PSS-Chitosan-PLGA fibers loaded with an antibiotic drug, ciprofloxacin hydrochloride, were produced using this method. The fibers provide modulated drug release with excellent mechanical properties, electrochemical performance and cytocompatibility, which hold great promise for the application of conductive electrospun scaffolds in regenerative medicine.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, with surgical resection of the tumor in conjunction with systemic chemotherapy the only potential curative therapy. Up to 80% of diagnosed cases are deemed unresectable, prompting the need for alternative treatment approaches. Herein, coaxial polymeric fibers loaded with two chemotherapeutic agents, gemcitabine (Gem) and paclitaxel (Ptx), are fabricated to investigate the effect of local drug delivery on PDAC cell growth in vitro and in vivo. A wet-spinning fabrication method to form a coaxial fiber with a polycaprolactone shell and alginate core loaded with Ptx and Gem, respectively, is used. In vitro, Gem+Ptx fibers display significant cytotoxicity as well as radiosensitizing properties toward PDAC cell lines greater than the equivalent free drugs, which may be attributed to a radiosensitizing effect of the polymers. In vivo studies assessing Gem+Ptx fiber efficacy found that Gem+Ptx fibers reduce tumor volume in a xenograft mouse model of PDAC. Importantly, no difference in mouse weight, circulating cytokines, or liver function is observed in mice treated with Gem+Ptx fibers compared to the empty fiber controls confirming the safety of the implant approach. With further development, Gem+Ptx fibers can improve the treatment of unresectable PDAC in the future.

In order to overcome the problems of reliability and accuracy often associated with electrochemical sensing in bioassays due to electrode surface fouling, we present an innovative antifouling surface coating based on lubricin (LUB). LUB is a large glycoprotein found in the articular joints of mammals with the ability to self-assemble on surfaces of different nature, creating an antiadhesive brush layer. This work demonstrates the size selective and antiadhesive properties of LUB coatings which prevent large biomolecules from adhering onto the electrode surface while simultaneously allowing smaller electroactive species to pass through the layer unimpeded. Electrochemical and surface characterisation experiments were performed using glassy carbon (GC), carbon black SPEs (CB), and reduced graphene oxide SPEs (rGO) in order to evaluate the antifouling capabilities of LUB coatings in solutions containing bovine serum albumin (BSA) and human saliva. The LUB coatings have been shown to exhibit outstanding antiadhesive properties, size selectivity, self-assembly as well as providing excellent electrochemistry in these highly fouling solutions.

For decades, electrode-tissue interfaces are pursued to establish electrical stimulation as a reliable means to control neuronal cells behavior. However, spreading of electrical currents in tissues limits its spatial precision. Thus, optical cues, such as near-infrared (NIR) light, are explored as alternatives. Presently, NIR stimulation requires higher energy input than electrical methods despite introduction of light absorbers, e.g., gold nanoparticles. As potential solution, NIR and electrical costimulation are proposed but with limited interfaces capable of sustaining this stimulation technique. Here, a novel electroactive nanocomposite with photoactive properties in the NIR range is constructed by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysulfosuccinimide sodium (EDC)/NHS conjugation of liquid crystal graphene oxide (LCGO) to protein-coated gold nanorods (AuNR). The liquid crystal graphene oxide-gold nanorod nanocomposite (LCGO-AuNR) is fabricated into a hydrophilic electrode-coating via drop-casting, making it appropriate for versatile electrode-tissue interface fabrication. UV-vis spectrophotometry results demonstrate that LCGO-AuNR presents an absorbance peak at 798 nm (NIR range). Cyclic voltammetry measurements further confirm its electroactive capacitive properties. Furthermore, LCGO-AuNR coating supports cell adhesion, proliferation, and differentiation of NG108-15 neuronal cells. This biocompatible interface is anticipated, with ideal electrical and optical properties for NIR and electrical costimulation, to enable further development of the technique for energy-efficient and precise neuronal cell modulation.

Carbon nanotubes (CNTs) have attracted significant attention because of their outstanding physical and chemical properties, and yet, their high natural tendency to form bundles, ropes, or aggregates, as a consequence of their strong π-π interactions, limits their solvent processing and further applications. Efficient processing solvents, mostly amide-based, that partially compensate for these strong inter-CNT π-π interactions have been widely reported. However, the yield of debundled/dispersed CNTs and the stability of subsequent dispersions in these solvents remain key challenges. Moreover, there are major concerns related to the large-scale use of conventional solvents, as they are fossil fuel based and intrinsically highly toxic, hence the need to identify environmentally friendly and safer alternatives. Herein, we address these challenges by using a ternary system composed of multiwalled CNTs (MWCNTs), tailored electron-deficient acceptors, and an organic solvent. Not only do the electron-deficient acceptors interrupt the inter-CNTs π-π interactions, thereby enabling the subsequent debundling and dispersion of MWCNTs aggregates in the solvent, they also act as stabilizers, after dispersion, by inhibiting inter-CNT π-π interactions and re-agglomeration. The use of electron acceptors increases the yield by a factor of 165 in N-methyl 2-pyrrolidone, improves the long-term stability of the debundled and dispersed MWCNTs, and reduces the energy input to only 30 min of mild bath sonication, compared with prolonged high-energy sonication reported in the literature. We also report for the first time, the use in MWCNT processing of a "green" biosolvent, dihydrolevoglucosenone, as an environmentally friendly and nontoxic alternative to the more conventional amide-based solvents.

Micro-capillaries, capable of light-regulated binding and qualitative detection of divalent metal ions in continuous flow, have been realised through functionalisation with spiropyran photochromic brush-type coatings. Upon irradiation with UV light, the coating switches from the passive non-binding spiropyran form to the active merocyanine form, which binds different divalent metal ions (Zn2+, Co2+, Cu2+, Ni2+, Cd2+), as they pass through the micro-capillary. Furthermore, the merocyanine visible absorbance spectrum changes upon metal ion binding, enabling the ion uptake to be detected optically. Irradiation with white light causes reversion of the merocyanine to the passive spiropyran form, with simultaneous release of the bound metal ion from the micro-capillary coating. This project has been funded by Science Foundation Ireland under the Insight initiative, grant SFI/1 /RC/2289. CD and DD also acknowledge the SFI under the Technology Innovation Development Award no. 16/TIDA/4183. F.B.L. acknowledges the Ramón y Cajal Programme (Ministerio de Economía y Competitividad) and Gobierno de España, Ministerio de Economía y Competitividad, with Grant No. BIO2016-80417-P.

Nano-texturing of surface by self-organised ablation ripples as well as modifications of internal volume of materials, transparent at the wavelength of laser irradiation, is gaining interest due to simplicity of direct laser writing/printing. With ultra-short laser pulses (τp < 1 ps) a wider range of structuring morphologies is accessible, namely, sub-wavelength ripples. The surface wave formed on the plasma-dielectric (air or substrate) explains difference of the formed pattern. These corresponding front- and back-side (in respect to the incoming laser beam) modes of laser structuring accounts for the ripple formation inside transparent materials, where a skin-layer plasma is formed. Emerging applications of nano-textured surfaces for bio-medical field are discussed.

Electrochemical detection of H-2 using scanning electrochemical microscopy (SECM) has shown to hold great promise as a sensitive characterization method with high spatial resolution for active surfaces generating H-2. Herein, the factors contributing to the current that is measured by SECM in generation/collection mode for H-2 detection are studied. In particular, the concentration gradient of H-2 at the substrate, the H-2/H+ recycling between the SECM tip and substrate and hemispherical profile of H-2 diffusion has been discussed. It was postulated that H-2/H+ recycling plays a dominant role in the oxidative current measured in generation/collection mode of SECM when the microelectrode is positioned in close vicinity of substrate. Copyright (C) 2015 John Wiley & Sons, Ltd.

Conductive polymers (CPs) are organic materials that hold great promise for biomedicine. Potential applications include in vitro or implantable electrodes for excitable cell recording and stimulation and conductive scaffolds for cell support and tissue engineering. In this study, we demonstrate the utility of electroactive CP polypyrrole (PPy) containing the anionic dopant dodecylbenzenesulfonate (DBS) to differentiate novel clinically relevant human neural stem cells (hNSCs). Electrical stimulation of PPy(DBS) induced hNSCs to predominantly β-III Tubulin (Tuj1) expressing neurons, with lower induction of glial fibrillary acidic protein (GFAP) expressing glial cells. In addition, stimulated cultures comprised nodes or clusters of neurons with longer neurites and greater branching than unstimulated cultures. Cell clusters showed a similar spatial distribution to regions of higher conductivity on the film surface. Our findings support the use of electrical stimulation to promote neuronal induction and the biocompatibility of PPy(DBS) with hNSCs and opens up the possibility of identifying novel mechanisms of fate determination of differentiating human stem cells for advanced in vitro modeling, translational drug discovery, and regenerative medicine.

Surface passivation of AZNd Mg alloy with Pr(NO 3 ) 3 is studied using scanning electrochemical microscopy (SECM) in surface generation/tip collection (SG/TC) and AC modes. Corrosion protection afforded by the Pr treatment and the degradation mechanism in a simulated biological environment was examined on a local scale and compared with non-treated AZNd. SG/TC mode results revealed a drastic decrease in H 2 evolution due to the Pr treatment. Mapping the local insulating characteristics using AC–SECM showed higher conductivity of the surface where H 2 evolution was most favorable.

The emerging field of nano-biology is borne from advances in our ability to control the structure of materials on finer and finer length-scales, coupled with an increased appreciation of the sensitivity of living cells to nanoscale topographical, chemical and mechanical cues. As we envisage and prototype nanostructured bioelectronic devices there is a crucial need to understand how cells feel and respond to nanoscale materials, particularly as material properties (surface energy, conductivity etc.) can be very different at the nanoscale than at the bulk. However, the patterning of organic bioelectronic materials is often not achievable using conventional fabrication techniques, especially on soft, biocompatible substrates. Nonconventional nanofabrication strategies are required. Dip-pen nanolithography is a nanofabrication technique which uses the nanoscale tip of an atomic force microscope to direct-write functional inks. Over the past decade, the technique has evolved as uniquely capable in the realm of bio-nanofabrication, with the capability to deposit both biomolecules and electrode materials. This review highlights this new tool for fabricating nanoscale bioelectronic devices, and for enabling heretofore unrealised experiments in the response of living cells to tailored nano-environments. We firstly introduce bioelectronics, followed by a survey of different lithography methods and their use to achieve paradigmic bioelectronic architectures. We then focus on dip-pen nanolithography, highlighting the range of bioelectronic materials and biomolecules which can be deposited using the technique, as well as its demonstrated use as a lithography tool in nano-biology. We discuss the progress made towards upscaling the DPN technology towards larger areas, in particular via the polymer pen approach.

Scanning electrochemical microscopy (SECM) in surface generation/tip collection mode is investigated as an assessment tool for studying the corrosion behaviour of magnesium in simulated biological fluid. The technique provides a local map of hydrogen (H2) evolution which alone can be used as a direct measure of corrosion. The H2 generated during corrosion of magnesium is oxidized at the probe(i.e. a Pt ultra micro-electrode);with the magnitude of the current generated due to oxidation being indicative of the intensity of H2 evolution at a local scale on the magnesium surface. This method was calibrated using a cathodically polarized Pt disk to simulate H2 evolution in a controlled condition on a homogeneous surface. Potential interference from dissolving Mg or high local pH was also investigated. The technique was implemented for studying H2 evolution at the surface of AZ31 as a model Mg alloy.SECM results combined with SEM-EDX and profilometry data revealed that local domains of higher H2 evolution on the surface of AZ31 are in close proximityof the observed pitting sites.

Nearly 30% of epilepsy cases cannot be adequately controlled with current medical treatments. The reasons for this are still not well understood, but there is a significant body of evidence pointing to the blood-brain barrier. Resective surgery can provide an alternative method of epilepsy control; however this treatment option is not suitable for most epilepsy sufferers. Local drug delivery through micro-injection to or implantation into the brain provides an innovative approach to bypass the blood-brain barrier for epilepsy treatment. In order to develop effective local delivery systems for anti-epilepsy drug (AED), we have prepared a variety of core-shell microcapsules via electrojetting, where a more hydrophobic polymer shell acts as a physical barrier to control the rate of drug release from the drug-loaded polymeric core. The resulting microcapsules demonstrate highly drug encapsulation efficiency, narrow size distribution and uniform morphology. Moreover, the release rate of AED can be modulated by controlling the morphologies of the core-shell microcapsules.

Electro-stimulated release was established using a novel, electro-conductive hydrogel system comprising Jeffamine polyetheramine and polyethylene glycol diglycidyl ether (PEGDGE) that was composited with reduced graphene oxide (rGO). The swelling response, morphology, mechanical and electrochemical properties of the composite hydrogel were investigated. Enhanced mechanical and electrical properties were observed with increased rGO content. Passive and electro-stimulated release of methyl orange (MO) from these gels was examined. A significant reduction in passive release of the dye was observed by incorporating rGO. Upon electrical stimulation, the release rate and dosage could be tuned through variation of the % w/w rGO, as well as the polarity and amplitude of the applied electric potential. A high level of control and flexibility was achieved demonstrating the applicability of this system for localised drug delivery applications.

Despite significant progress in developing new drugs for seizure control, epilepsy still affects 1% of the global population and is drug-resistant in more than 30% of cases. To improve the therapeutic efficacy of epilepsy medication, a promising approach is to deliver anti-epilepsy drugs directly to affected brain areas using local drug delivery systems. The drug delivery systems must meet a number of criteria, including high drug loading efficiency, biodegradability, neuro-cytocompatibility and predictable drug release profiles. Here we report the development of fibre- and sphere-based microcapsules that exhibit controllable uniform morphologies and drug release profiles as predicted by mathematical modelling. Importantly, both forms of fabricated microcapsules are compatible with human brain derived neural stem cells and differentiated neurons and neuroglia, indicating clinical compliance for neural implantation and therapeutic drug delivery.

Biocompatible conductive tough hydrogels represent a new class of advanced materials combining the properties of tough hydrogels and biocompatible conductors. Here, a simple method, to achieve a self-assembled tough elastomeric composite structure that is biocompatible, conductive, and with high flexibility, is reported. The hydrogel comprises polyether-based liner polyurethane (PU), poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly(4-styrenesulfonate) (PSS), and liquid crystal graphene oxide (LCGO). The polyurethane hybrid composite (PUHC) containing the PEDOT:PSS, LCGO, and PU has a higher electrical conductivity (10×), tensile modulus (>1.6×), and yield strength (>1.56×) compared to respective control samples. Furthermore, the PUHC is biocompatible and can support human neural stem cell (NSC) growth and differentiation to neurons and supporting neuroglia. Moreover, the stimulation of PUHC enhances NSC differentiation with enhanced neuritogenesis compared to unstimulated cultures. A model describing the synergistic effects of the PUHC components and their influence on the uniformity, biocompatibility, and electromechanical properties of the hydrogel is presented.

Background/Objectives There has been minimal improvement in the prognosis of pancreatic cancer cases in the past 3 decades highlighting the crucial need for more effective therapeutic approaches. A drug delivery system capable of locally delivering high concentrations of chemotherapeutics directly at the site of the tumor is clearly required. The aim of this study was to fabricate and characterize the biophysical properties of gemcitabine-eluting wet-spun polymeric fibers for localized drug delivery applications. Methods/Results Fibers spun from alginate or chitosan solutions with or without the anticancer drug gemcitabine had a uniform surface area, were internally homogeneous and ranged from 50-120 μm in diameter. Drug encapsulation ranged from 13-52%, depending on the type and concentration of polymer used. Gemcitabine displayed first-order release kinetics where 64–82% of the loaded drug was rapidly released within the first 10 h followed by a sustained release over the next 134 h. A time dependent inhibition of ex vivo tumor spheroid growth and cell viability was observed after incubation with gemcitabine-loaded fibers but not control fibers. Conclusion With further development these studies could lead to the manufacture of a safe and effective delivery system designed to combat non-resectable pancreatic cancer for which currently there is minimal chance of cure.

Drug delivery from 3-dimensional (3D) structures is a rapidly growing area of research. It is essential to achieve structures wherein drug stability is ensured, the drug loading capacity is appropriate and the desired controlled release profile can be attained. Attention must also be paid to the development of appropriate fabrication machinery that allows 3D drug delivery systems (DDS) to be produced in a simple, reliable and reproducible manner. The range of fabrication methods currently being used to form 3D DDSs include electrospinning (solution and melt), wet-spinning and printing (3-dimensional). The use of these techniques enables production of DDSs from the macro-scale down to the nano-scale. This article reviews progress in these fabrication techniques to form DDSs that possess desirable drug delivery kinetics for a wide range of applications.

Different modes of scanning electrochemical mapping (SECM) such as surface generation/tip collection (SG/TC), amperometry, AC-SECM and potentiometry were employed to characterize the active/passive domains, hydrogen gas (H2) evolution and local pH on a corroding surface of AZ31 in simulated biological fluid (SBF). It was found that the main domains of H2 evolution are associated with lower insulating properties of the surface as well as higher local pH. The near surface pH was found to be highly alkaline indicating that, even in a buffered solution such as SBF, the local pH on a corroding AZ31 surface can be significantly different to the bulk pH.

The controlled deposition of attolitre volumes of liquids may engender novel applications such as soft, nano-tailored cell-material interfaces, multi-plexed nano-arrays for high throughput screening of biomolecular interactions, and localized delivery of reagents to reactions confined at the nano-scale. Although the deposition of small organic molecules from an AFM tip, known as dip-pen nanolithography (DPN), is being continually refined, AFM deposition of liquid inks is not well understood, and is often fraught with inconsistent deposition rates. In this work, the variation in feature-size over long term printing experiments for four model inks of varying viscosity is examined. A hierarchy of recurring phenomena is uncovered and there are attributed to ink movement and reorganisation along the cantilever itself. Simple analytical approaches to model these effects, as well as a method to gauge the degree of ink loading using the cantilever resonance frequency, are described. In light of the conclusions, the various parameters which need to be controlled in order to achieve uniform printing are dicussed. This work has implications for the nanopatterning of viscous liquids and hydrogels, encompassing ink development, the design of probes and printing protocols.

New insights into electrochemical kinetics of the flavin adenine dinucleotide (FAD) redox center of glucose-oxidase (GlcOx) immobilized on reduced graphene oxide (rGO), single- and multiwalled carbon nanotubes (SW and MWCNT), and combinations of rGO and CNTs have been gained by application of Fourier transformed AC voltammetry (FTACV) and simulations based on a range of models. A satisfactory level of agreement between experiment and theory, and hence establishment of the best model to describe the redox chemistry of FAD, was achieved with the aid of automated e-science tools. Although still not perfect, use of Marcus theory with a very low reorganization energy (≤0.3 eV) best mimics the experimental FTACV data, which suggests that the process is gated as also deduced from analysis of FTACV data obtained at different frequencies. Failure of the simplest models to fully describe the electrode kinetics of the redox center of GlcOx, including those based on the widely employed Laviron theory is demonstrated, as is substantial kinetic heterogeneity of FAD species. Use of a SWCNT support amplifies the kinetic heterogeneity, while a combination of rGO and MWCNT provides a more favorable environment for fast communication between FAD and the electrode.

Rational control over the formation and processability, and consequently final properties of graphene oxide liquid crystalline dispersions has been a long-standing goal in the development of bottom-up device fabrication processes. Here we report, the principal conditions through which such levels of control can be exercised to fine-tune dispersion properties for further processing.

Biodegradable magnesium alloys are advantageous in various implant applications, as they reduce the risks associated with permanent metallic implants. However, a rapid corrosion rate is usually a hindrance in biomedical applications. Here we report a facile two step procedure to introduce multifunctional, anti-corrosive coatings on Mg alloys, such as AZ31. The first step involves treating the NaOH-activated Mg with bistriethoxysilylethane to immobilize a layer of densely crosslinked silane coating with good corrosion resistance; the second step is to impart amine functionality to the surface by treating the modified Mg with 3-amino-propyltrimethoxysilane. We characterized the two-layer anticorrosive coating of Mg alloy AZ31 by Fourier transform infrared spectroscopy, static contact angle measurement and optical profilometry, potentiodynamic polarization and AC impedance measurements. Furthermore, heparin was covalently conjugated onto the silane-treated AZ31 to render the coating haemocompatible, as demonstrated by reduced platelet adhesion on the heparinized surface. The method reported here is also applicable to the preparation of other types of biofunctional, anti-corrosive coatings and thus of significant interest in biodegradable implant applications.

Aqueous dispersions of reduced graphene oxide (rGO) and multi walled carbon nanotubes (MWCNT) were fabricated through a modified chemical reduction method. The significant advantage of the method developed here is the omission of any stabilising compound or organic solvent to obtain stable rGO–MWCNT dispersions. Significantly biological entities, in this case the enzyme glucose oxidase (GOx), can be successfully incorporated into the dispersion. These dispersions were characterised using XPS, SEM, zeta potential and particle size measurements which showed that the dispersion stability is not sacrificed with the addition of GOx, and significantly, the electrical properties of the rGO and MWCNTs are maintained. In this study, rGO acts as an effective dispersing agent for MWCNTs and does not affect the solubility or electroactivity of the GOx. Bioelectrodes fabricated from these rGO–MWCNT–GOx dispersions were characterised electrochemically to test their feasibility in facilitating direct electron transfer (DET) from the redox centre of the enzyme to the electrode. The DET results showed that the specific catalytic current generated at an optimised rGO–MWCNT–GOx electrode was 72 μA/μg GOx, which is 144 times more efficient than other literature values for similar systems. The remarkable specific catalytic current can be attributed to the use of purified enzyme, the efficiency of charge transfer within the rGO–MWCNT composite and the ability of the electrode to facilitate direct electron transfer.

This paper reports on a facile synthesis method for reduced graphene oxide (rGO)/multi-walled carbon nanotubes (MWNTs) nanocomposites. The initial step involves the use of graphene oxide to disperse the MWNTs, with subsequent reduction of the resultant graphene oxide/MWNTs composites using l-ascorbic acid (LAA) as a mild reductant. Reduction by LAA preserves the interaction between the rGO sheets and MWNTs. The dispersion-containing rGO/MWNTs composites was characterized and electrophoretically deposited anodically onto glassy carbon electrodes to form high surface area films for capacitance testing. Pseudo capacitance peaks were observed in the rGO/MWNTs composite electrodes, resulting in superior performance with capacitance values up to 134.3 F g−1 recorded. This capacitance value is higher than those observed for LAA-reduced GO (LAA-rGO) (63.5 F g−1), electrochemically reduced GO (EC-rGO) (27.6 F g−1), or electrochemically reduced GO/MWNTs (EC-rGO/MWNTs) (98.4 F g−1)-based electrodes.

In this paper, attempts to dope polypyrrole (PPy) with two small sized anionic drugs, diclofenac sodium salt (NaDF) and valproic acid sodium salt (NaVPA), are described. For PPy doped with DF−, unusual patterns in growth and morphology were observed. During the deposition of the polymer, the rate of electropolymerisation decreased with increasing time and higher applied potentials. The polymer had features of an insulating film, while SEM confirmed the presence of crystal-like shards on the surface of the polymer. Analyses of these crystals indicate them to be drug that may have precipitated out of solution. These findings suggest that insoluble drug crystals are formed during electropolymerisation. The formation of PPy doped with a small soluble anti-epilepsy anionic drug, VPA−, was also studied; however it was not possible to incorporate this drug during electrochemical polymerisation. Again, this was explained in terms of the equilibrium between the anion and the acid forms of VPA. At pH values below 5.6, the equilibrium of the VPA− is shifted towards the insoluble HVPA. As the monomer is oxidised, there is a decrease in the local pH in the vicinity of the electrode and this causes the HVPA to precipitate from solution. This, in turn, prevents any PPy from being deposited at the electrode.

This blinded controlled prospective randomized study investigates the biocompatibility of polypyrrole (PPy) polymer that will be used for intracranial triggered release of anti-epileptic drugs (AEDs). Three by three millimeters PPy are implanted subdurally in six adult female genetic absence epilepsy rats from Strasbourg. Each rat has a polymer implanted on one side of the cortex and a sham craniotomy performed on the other side. After a period of seven weeks, rats are euthanized and parallel series of coronal sections are cut throughout the implant site. Four series of 15 sections are histological (hematoxylin and eosin) and immunohistochemically (neuron-specific nuclear protein, glial fibrillary acidic protein, and anti-CD68 antibody) stained and evaluated by three investigators. The results show that implanted PPy mats do not induce obvious inflammation, trauma, gliosis, and neuronal toxicity. Therefore the authors conclude the PPy used offer good histocompatibility with central nervous system cells and that PPy sheets can be used as intracranial, AED delivery implant.

The current experiment investigated the ability of coaxial electrospun poly(D,L-lactide-co-glycolide) (PLGA) biodegradable polymer implants loaded with the antiepileptic drugs (AED) lacosamide to reduce seizures following implantation above the motor cortex in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). In this prospective, randomized, masked experiments, GAERS underwent surgery for implantation of skull electrodes (n=6), skull electrodes and blank polymers (n=6), or skull electrodes and lacosamide loaded polymers (n=6). Thirty-minute electroencephalogram (EEG) recordings were started at day 7 after surgery and continued for eight weeks. The number of SWDs and mean duration of one SWD were compared week-by-week between the three groups. There was no difference in the number of SWDs between any of the groups. However, the mean duration of one SWD was significantly lower in the lacosamide polymer group for up to 7 weeks when compared to the control group (0.004

Epilepsy is a neurological disorder characterised by spontaneous seizures. Over one third of patients receive insufficient benefit from oral anti-epileptic drug (AED) therapy, and continue to experience seizures whilst on medication. Epilepsy researchers are consequently seeking new ways to deliver AEDs directly to the seizure focus in the brain in order to deliver higher, more effective doses to the seizure focus whilst bypassing the remainder of the brain and body to prevent side effects. The focus of this review will be polymer-based implants, which are polymeric devices loaded with AED that are designed for implantation at the seizure focus in order to achieve gradual, continuous release of AED direct into the region of the brain responsible for seizures. Polymer-based implants produced for epilepsy to date are based on a range of polymers, both biodegradable and non-biodegradable, and range from simple materials development studies through to investigations of implants in animal models of seizures and epilepsy, with varying degrees of success. This review describes the range of methods employed to manufacture polymer-based implants and compares their advantages and potential appeal to industry, and describes and compares the results and successes of polymer-based materials and devices produced to date for the treatment of epilepsy. We also discuss disadvantages and hurdles to be overcome in the field, and describe our predictions for advances to be made in the field in the coming decade.

Some of the most exciting recent advances in conducting polymer synthesis have centered around the method of vapor phase polymerization (VPP) of thin films. However, it is not known whether the VPP process can proceed using significantly reduced volumes of oxidant and therefore be implemented as part of nanolithography approach. Here, we present a strategy for submicrometer scale patterning of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) via in situ VPP. Attolitre (10(-18) L) volumes of oxidant "ink" are controllably deposited using dip-pen nanolithography (DPN). DPN patterning of the oxidant ink is facilitated by the incorporation of an amphiphilic block copolymer thickener, an additive that also assists with stabilization of the oxidant. When exposed to EDOT monomer in a VPP chamber, each deposited feature localizes the synthesis of conducting PEDOT structures of several micrometers down to 250 nm in width. PEDOT patterns are characterized by atomic force microscopy (AFM), conductive AFM, two probe electrical measurement, and micro-Raman spectroscopy, evidencing in situ vapor phase synthesis of conducting polymer at a scale (picogram) which is much smaller than that previously reported. Although the process of VPP on this scale was achieved, we highlight some of the challenges that need to be overcome to make this approach feasible in an applied setting.

The term “bionics” is synonymous with the term “biomimetics” and in this context refers to the integration of human engineered devices to take advantage of functional mechanisms and structures resident in nature. The use of electrical conductors to transmit charge into and out of biological systems to affect biological processes has been the source of great scientific interest. This has inspired many to explore the possible use of electrical stimulation in promoting positive health outcomes. Advances in medical bionics technology are dependent upon eliciting precise control of the electrical energy to deliver beneficial health outcomes. The advent of carbon-based organic conductors now provides the platform for unprecedented possibilities by which the electrical energy can be used to modulate the function of medical devices. The use of organic conductors in the field of bionics, and in particular medical bionics, as that involved with the development of devices that enable the effective integration of biology (nature) and electronics to achieve a targeted functional outcome is explored.

The as-synthesised carbon nanotube nanoweb modified carbon fibre paper (CNT-NW/CFP) was investigated to study the effect of surface protein adsorption in electrochemical activities using immunoglobulin G (IgG) and human serum albumin (HSA). Detail chemical characterisation was carried out using 125I radiolabeling, cyclic voltammetry and electrochemical impedance spectroscopy. Both HSA and IgG were adsorbed onto the electrode at levels of approximately 120 mg/m2. Cyclic voltammetry indicated that the surface-adsorbed protein had a detrimental effect on oxidation/reduction of ferri/ferricyanide whilst EIS spectra revealed a slight increase in impedance and decrease in capacitance. Keywords: Carbon nanotubes, Protein adsorption, Double layer capacitance, Electrochemical impedance spectroscopy

Conducting polymers provide suitable substrates for the in vitro study of excitable cells, including skeletal muscle cells, due to their inherent conductivity and electroactivity. The thiophene family of conducting polymers offers unique flexibility for tailoring of polymer properties as a result of the ease of functionalization of the parent monomer. This article describes the preparation of films and electrospun fibers from an ester-functionalized organic solvent-soluble polythiophene (poly-octanoic acid 2-thiophen-3-yl-ethyl ester) and details the changes in properties that result from post-polymerization hydrolysis of the ester linkage. The polymer films supported the proliferation and differentiation of both primary and transformed skeletal muscle myoblasts. In addition, aligned electrospun fibers formed from the polymers provided scaffolds for the guided differentiation of linearly aligned primary myotubes, suggesting their suitability as three-dimensional substrates for the in vitro engineering of skeletal muscle tissue.