Recently, phosphorescent iridium complexes have demonstrated great potential as anticancer and imaging agents. Dopamine is a melanin-like mimic of mussel adhesive protein that can self-polymerize to form polydopamine (PDA) nanoparticles that demonstrate favorable biocompatibility, near-infrared absorption, and photothermal effects. Herein, PDA nanoparticles are functionalized with β-cyclodextrin (CD) substitutions, which are further assembled with adamantane-modified arginine-glycine-aspartic acid (Ad-RGD) tripeptides to target integrin-rich tumor cells. The thus formed PDA-CD-RGD nanoparticles can deliver a phosphorescent iridium(III) complexes LysoIr ([Ir(ppy)2(l)]PF6, ppy = 2-phenylpyridine, L = (1-(2-quinolinyl)-β-carboline) to form a theranostic platform LysoIr@PDA-CD-RGD. It is demonstrated that LysoIr@PDA-CD-RGD can be applied for targeted combined cancer photothermal-chemotherapy and thermal/photoacoustic/two-photon phosphorescence lifetime imaging under both in vitro and in vivo conditions. This work provides a useful strategy to construct multifunctional nanocomposites for the optimization of metal-based anticancer agents for further biomedical applications.

Nanocomposites based on two conducting polymers, polyaniline (PANI) and polypyrrole (Ppy), with embedded glucose oxidase (GOx) and 6 nm size gold nanoparticles (AuNPs_(6nm)) or gold-nanoclusters formed from chloroaurate ions (AuCl₄^-), were synthesized by enzyme-assisted polymerization. Charge (electron) transfer in systems based on PANI/AuNPs_(6nm)-GOx, PANI/AuNPs_(AuCl4^-₎-GOx, Ppy/AuNPs_(6nm)-GOx and Ppy/AuNPs_(AuCl4^-₎-GOx nanocomposites was investigated. Cyclic voltammetry (CV)-based investigations showed that the reported polymer nanocomposites are able to facilitate electron transfer from enzyme to the graphite rod (GR) electrode. Significantly higher anodic current and well-defined red-ox peaks were observed at a scan rate of 0.10 V s^-1. Logarithmic function of anodic current (log I_pa), which was determined by CV-based experiments performed with glucose, was proportional to the logarithmic function of a scan rate (log v) in the range of 0.699-2.48 mV s^-1, and it indicates that diffusion-controlled electrochemical processes were limiting the kinetics of the analytical signal. The most efficient nanocomposite structure for the design of the reported glucose biosensor was based on two-day formed Ppy/AuNPs_(AuCl4^-₎-GOx nanocomposites. GR/Ppy/AuNPs_(AuCl4^-₎-GOx was characterized by the linear dependence of the analytical signal on glucose concentration in the range from 0.1 to 0.70 mmol L^-1, the sensitivity of 4.31 mA mM cm^-2, the limit of detection of 0.10 mmol L^-1 and the half-life period of 19 days.

Keywords: biofuel cell; conducting polymers; cyclic voltammetry; glucose biosensor; glucose oxidase; gold nanoparticles; polyaniline; polymer nanocomposite; polypyrrole.

Oncogenic transcriptional coregulators C-terminal Binding Protein (CtBP) 1 and 2 possess regulatory d-isomer specific 2-hydroxyacid dehydrogenase (D2-HDH) domains that provide an attractive target for small molecule intervention. Findings that the CtBP substrate 4-methylthio 2-oxobutyric acid (MTOB) can interfere with CtBP oncogenic activity in cell culture and in mice confirm that such inhibitors could have therapeutic benefit. Recent crystal structures of CtBP 1 and 2 revealed that MTOB binds in an active site containing a dominant tryptophan and a hydrophilic cavity, neither of which are present in other D2-HDH family members. Here, we demonstrate the effectiveness of exploiting these active site features for the design of high affinity inhibitors. Crystal structures of two such compounds, phenylpyruvate (PPy) and 2-hydroxyimino-3-phenylpropanoic acid (HIPP), show binding with favorable ring stacking against the CtBP active site tryptophan and alternate modes of stabilizing the carboxylic acid moiety. Moreover, ITC experiments show that HIPP binds to CtBP with an affinity greater than 1000-fold over that of MTOB, and enzymatic assays confirm that HIPP substantially inhibits CtBP catalysis. These results, thus, provide an important step, and additional insights, for the development of highly selective antineoplastic CtBP inhibitors.

Highly uniform core-shell composites, polypyrrole@polyaniline (PPy@PANI), have been successfully constructed by directing the polymerization of aniline on the surface of PPy microspheres. The thickness of PANI shells, from 30 to 120 nm, can be well controlled by modulating the weight ratio of aniline and PPy microspheres. PPy microspheres with abundant carbonyl groups have very strong affinity to the conjugated chains of PANI, which is responsible for the spontaneous formation of uniform core-shell microstructures. However, the strong affinity between PPy microspheres and PANI shells does not promote the diffusion or reassembly of two kinds of conjugated chains. Coating PPy microspheres with PANI shells increases the complex permittivity and creates the mechanism of interfacial polarization, where the latter plays an important role in increasing the dielectric loss of PPy@PANI composites. With a proper thickness of PANI shells, the moderate dielectric loss will produce well matched characteristic impedance, so that the microwave absorption properties of these composites can be greatly enhanced. Although PPy@PANI composites herein consume the incident electromagnetic wave by absolute dielectric loss, their performances are still superior or comparable to most PANI-based composites ever reported, indicating that they can be taken as a new kind of promising lightweight microwave absorbers. More importantly, microwave absorption of PPy@PANI composites can be simply modulated not only by the thickness of the absorbers, but also the shell thickness to satisfy the applications in different frequency bands.

Rectal cancer is a common type of colorectal cancer with high mortality and morbidity. The objective of this study was to identify gene signatures and uncover the potential mechanisms during rectal cancer samples. The gene expression profiles of GSE87211 data set were downloaded from GEO (Gene Expression Omnibus) database. The GSE87211 data set contained 2363 samples, including 203 rectal cancer samples and 160 matched mucosa control samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, and protein-protein interaction network of differentially expressed genes (DEGs) was performed by Cytoscape. Then, Gene Expression Profiling Interactive Analysis (GEPIA) was applied to get the hub genes expression level and survival analysis between rectum adenocarcinoma (READ) tissues and normal tissues. In total, 846 DEGs were identified, including 402 upregulated genes and 444 downregulated genes. GO analysis showed that upregulated DEGs were enriched in inflammatory response, signal transduction, cell adhesion, immune response, and positive regulation of cell proliferation. KEGG pathway analysis showed that upregulated DEGs were enriched in cytokine-cytokine receptor interaction, Pi3K-Akt signaling pathway, and chemokine signaling pathway. The top 20 hub genes contained IL8, CXCR1, SSTR2, SST, CXCR2, GALR1, GAL, CXCL1, SSTR1, NPY1R, NPY, AGT, PPY, PPBP, CXCL2, CXCL6, CXCL11, CXCL3, GNG4, and GNGT1, and only four genes significantly increased expression levels with obvious changes of survival analysis in READ tissues based on GEPIA. Our study indicated that identified DEGs might promote our understanding of molecular mechanisms, which might be used as molecular targets or diagnostic biomarkers for the treatment of rectal cancer.

We report molecular designing strategies to enhance the effective visible-light absorption of cyclometalated Ir(III) complexes. Cationic cyclometalated Ir(III) complexes were prepared in which boron-dipyrromethene (Bodipy) units were attached to the 2,2'-bipyridine (bpy) ligand via -C≡C- bonds at either the meso-phenyl (Ir-2) or 2 position of the π core of Bodipy (Ir-3). For the first time the effect of π conjugating (Ir-3) or tethering (Ir-2) of a light-harvesting chromophore to the coordination center on the photophysical properties was compared in detail. Ir(ppy)2(bpy) (Ir-1; ppy = 2-phenylpyridine) was used as model complex, which gives the typical weak absorption in visible range (ε < 4790 M(-1) cm(-1) in region>> 400 nm). Ir-2 and Ir-3 showed much stronger absorption in the visible range (ε = 71,400 M(-1) cm(-1) at 499 nm and 83,000 M(-1) cm(-1) at 527 nm, respectively). Room-temperature phosphorescence was only observed for Ir-1 (λ(em) = 590 nm) and Ir-3 (λ(em) = 742 nm). Ir-3 gives RT phosphorescence of the Bodipy unit. On the basis of the 77 K emission spectra, nanosecond transient absorption spectra, and spin density analysis, we proposed that Bodipy-localized long-lived triplet excited states were populated for Ir-2 (τT = 23.7 μs) and Ir-3 (87.2 μs). Ir-1 gives a much shorter triplet-state lifetime (0.35 μs). Complexes were used as singlet oxygen ((1)O2) photosensitizers in photooxidation. The (1)O2 quantum yield of Ir-3 (ΦΔ = 0.97) is ca. 2-fold of Ir-2 (ΦΔ = 0.52). Complexes were also used as triplet photosensitizer for TTA upconversion; upconversion quantum yields of 1.2% and 2.8% were observed for Ir-2 and Ir-3, respectively. Our results proved that the strong absorption of visible light of Ir-2 failed to enhance production of a triplet excited state. These results are useful for designing transition metal complexes that show effective strong visible-light absorption and long-lived triplet excited states, which can be used as ideal triplet photosensitizers in photocatalysis and TTA upconversion.

Electrically conductive hyaluronic acid (HA) hydrogels incorporated with single-walled carbon nanotubes (CNTs) and/or polypyrrole (PPy) were developed to promote differentiation of human neural stem/progenitor cells (hNSPCs). The CNT and PPy nanocomposites, which do not easily disperse in aqueous phases, dispersed well and were efficiently incorporated into catechol-functionalized HA (HA-CA) hydrogels by the oxidative catechol chemistry used for hydrogel cross-linking. The prepared electroconductive HA hydrogels provided dynamic, electrically conductive three-dimensional (3D) extracellular matrix environments that were biocompatible with hNSPCs. The HA-CA hydrogels containing CNT and/or PPy significantly promoted neuronal differentiation of human fetal neural stem cells (hfNSCs) and human induced pluripotent stem cell-derived neural progenitor cells (hiPSC-NPCs) with improved electrophysiological functionality when compared to differentiation of these cells in a bare HA-CA hydrogel without electroconductive motifs. Calcium channel expression was upregulated, depolarization was activated, and intracellular calcium influx was increased in hNSPCs that were differentiated in 3D electroconductive HA-CA hydrogels; these data suggest a potential mechanism for stem cell neurogenesis. Overall, our bioinspired, electroconductive HA hydrogels provide a promising cell-culture platform and tissue-engineering scaffold to improve neuronal regeneration.

With the rapid development of portable electronics, solid-state flexible supercapacitors (SCs) are considered as one of the promising energy devices in powering electronics because of their intrinsic advantages. Polypyrrole (PPy) is an ideal electrode material in constructing flexible SCs owing to its high electrochemical activity and inherent flexibility, although its relatively low capacitance and poor cycling stability are still worthy of improvement. Herein, through the innovative introduction of black phosphorus (BP) nanosheets, we developed a laminated PPy/BP self-standing film with enhanced capacitance and cycling stability via a facile one-step electrochemical deposition method. The film exhibits a high capacitance of 497.5 F g-1 (551.7 F cm-3) and outstanding cycling stability of 10 000 charging/discharging cycles, thanks to BP nanosheets inducing laminated assembly which hinder dense and disordered stacking of PPy during electrodeposition, consequently providing a precise pathway for ion diffusion and electron transport together with alleviation of the structural deterioration during charge/discharge. The flexible SC fabricated by laminated films delivers a high capacitance of 452.8 F g-1 (7.7 F cm-3) besides its remarkable mechanical flexibility and cycling stability. Our facile strategy paves the way to improve the electrochemical performance of PPy-based SC that could serve as promising flexible energy device for portable electronics.

Pseudomonas aeruginosa is an opportunistic human pathogen which exhibits its property of pathogenesis due to several factors, including the formation of biofilm and production of several virulence factors. Development of resistance properties against antibiotics leads to the discovery of certain alternative strategies to combat its pathogenesis. In the present study, a highly stable, biocompatible and water soluble nanocomposites (NCs) are synthesized from chitosan (CS) and the polypyrrole (PPy). The resultant chitosan-polypyrrole nanocomposites (CS-PPy NCs) inhibit the establishment of biofilm and also eradicate the preformed matured biofilm formed by P. aeruginosa. CS-PPy NCs inhibit the hemolytic and protease activities of P. aeruginosa. The NCs significantly reduce the production of many virulence factors such as pyocyanin, pyroverdine and rhamnolipid. CS-PPy NCs also suppress the bacterial motility such as swimming and swarming. The present study showed that highly stable CS-PPy NCs act as a potent antibiofilm and antivirulence drug for the treatment of P. aeruginosa infection.

The electrochemiluminescence (ECL) of Ir(ppy)3 (ppy = 2-phenylpyridine) is reported in acetonitrile (CH3CN), mixed CH3CN/H20 (50:50 v/v), and aqueous (0.1 M KH2PO4) solutions with tri-n-propylamine as an oxidative-reductive coreactant. ECL efficiencies (phi(ecl), photons emitted per redox event) of 0.00092 in aqueous, 0.0044 in mixed, and 0.33 in CH3CN solutions for Ir(ppy)3 were obtained using Ru(bpy)3(2+) (bpy = 2,2'-bipyridine) as a relative standard (phi(ecl) = 1). Photoluminescence (PL) efficiencies of 0.039, 0.050, and 0.069 were obtained in aqueous, mixed, and acetonitrile solutions, respectively, compared to Ru(bpy)3(2+) (phi(em) = 0.042). The ECL spectra were identical to photoluminescence spectra (lambda(max) approximately equal to 517 nm), indicating formation of the same metal-to-ligand (MLCT) excited states in both ECL and PL. The ECL is linear over several orders of magnitude in mixed and acetonitrile solution with theoretical detection limits (blank plus three times the standard deviation of the noise) of 1.23 nM in CH3CN and 0.23 microM in CH3CN/ H20 (50:50 v/v).

Scaffolds constituted by micro and nanofibers of silk fibroin were obtained by electrospinning. Fibers of fibroin meshes were coated with polypyrrole (pPy) by chemical polymerization; chemical linkages between polymers were observed by SEM and IR spectroscopy. Mechanical resistance of the meshes was improved by polypyrrole coating. Furthermore, coated meshes present a high electroactivity allowing anion storage and delivery during oxidation/reduction reactions in aqueous solutions. Uncoated and pPy coated materials support the adherence and proliferation of adult human mesenchymal stem cells (ahMSCs) or human fibroblasts (hFb). The bioactivity of fibroin mesh overcomes that of the polypyrrole coated meshes.

BACKGROUND

International financing for malaria increased more than 18-fold between 2000 and 2011; the largest source came from The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). Countries have made substantial progress, but achieving elimination requires sustained finances to interrupt transmission and prevent reintroduction. Since 2011, global financing for malaria has declined, fueling concerns that further progress will be impeded, especially for current malaria-eliminating countries that may face resurgent malaria if programs are disrupted.

OBJECTIVE

This study aims to 1) assess past total and Global Fund funding to the 34 current malaria-eliminating countries, and 2) estimate their future funding needs to achieve malaria elimination and prevent reintroduction through 2030.

METHODS

Historical funding is assessed against trends in country-level malaria annual parasite incidences (APIs) and income per capita. Following Kizewski et al. (2007), program costs to eliminate malaria and prevent reintroduction through 2030 are estimated using a deterministic model. The cost parameters are tailored to a package of interventions aimed at malaria elimination and prevention of reintroduction.

RESULTS

The majority of Global Fund-supported countries experiencing increases in total funding from 2005 to 2010 coincided with reductions in malaria APIs and also overall GNI per capita average annual growth. The total amount of projected funding needed for the current malaria-eliminating countries to achieve elimination and prevent reintroduction through 2030 is approximately US$8.5 billion, or about $1.84 per person at risk per year (PPY) (ranging from $2.51 PPY in 2014 to $1.43 PPY in 2030).

CONCLUSIONS

Although external donor funding, particularly from the Global Fund, has been key for many malaria-eliminating countries, sustained and sufficient financing is critical for furthering global malaria elimination. Projected cost estimates for elimination provide policymakers with an indication of the level of financial resources that should be mobilized to achieve malaria elimination goals.

Polypyrrole (PPy) nanotubes have been fabricated by reverse microemulsion polymerization in an apolar solvent, and factors affecting the formation of PPy nanotubes have also been investigated.

Conversion/alloying reactions, in which more lithium ions are involved, are severely handicapped by the dramatic volume changes. A facile and versatile strategy has been developed for integrating the SnO2 nanorod array in the PPy nanofilm for providing a flexible confinement for anchoring each nanorod and maintaining the entire structural integrity and providing sustainable contact; therefore, exhibiting much more stable cycling stability (701 mA h g(-1) after 300 cycles) and better high-rate capability (512 mA h g(-1) at 3 A g(-1)) when compared with the core-shell SnO2-PPy NA.

To localize binding sites for peptide YY (PYY) in the pancreas we utilized a slide-mount autoradiographic technique on frozen sections of rat pancreas incubated with 125I-Tyr36-PPY. Saturable autoradiographic labeling was located over pancreatic blood vessels, whereas islets, acinar cells, ducts, and neural elements did not appear to be specifically labeled. Isolated vascular fragments were prepared by collagenase digestion of rat pancreas. Binding experiments with 125I-Tyr36-PYY showed saturable binding to the fraction enriched in blood vessels but not to acini. Inhibition of 125I-Tyr36-PYY binding by nonradioactive neuropeptide Y (NPY) and PYY were similar, with half-maximal inhibition at 31.2 +/- 5 pM (n = 6); the potency of pancreatic polypeptide (PP) was 10,000 times lower. The binding site was classified as belonging to a Y1 type of NPY and/or PYY receptors, since [Leu31,Pro34]NPY, a specific Y1-receptor agonist, inhibited binding similar to NPY. To further localize the bound [125I-Tyr36]PYY within the blood vessels, light- and electron-microscopic autoradiographs were prepared and quantitated. Autoradiographic grains were located predominantly over vascular smooth muscle cells, although saturable localization was also seen over endothelial cells. It is concluded that in the pancreas Y1 receptors are predominantly located on vascular smooth muscle cells.

The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein. Immunohistochemistry showed that Glis3-EGFP was not detectable during early pancreatic development (E11.5 and E12.5) and at E13.5 and 15.5 was not expressed in Ptf1a+ cells in the tip domains indicating that Glis3 is not expressed in multipotent pancreatic progenitors. Glis3 was first detectable at E13.5 in the nucleus of bipotent progenitors in the trunk domains, where it co-localized with Sox9, Hnf6, and Pdx1. It remained expressed in preductal and Ngn3+ endocrine progenitors and at later stages becomes restricted to the nucleus of pancreatic beta and PP cells as well as ductal cells. Glis3-deficiency greatly reduced, whereas exogenous Glis3, induced Ppy expression, as reported for insulin. Collectively, our study demonstrates that Glis3 protein exhibits a temporal and cell type-specific pattern of expression during embryonic and neonatal pancreas development that is consistent with a regulatory role for Glis3 in promoting endocrine progenitor generation, regulating insulin and Ppy expression in beta and PP cells, respectively, and duct morphogenesis.

A sophisticated hierarchical nanoarray consisting of a conducting polymer (polypyrrole, PPy) core and layered double hydroxide (LDH) shell are synthesized via a facile two-step electrosynthesis method. The obtained PPy@LDH-based flexible all-solid-state supercapacitor meets the requirements of both high energy/power output and long-term endurance, which can be potentially used in highly-efficient and stable energy storage.

Ultrahigh density arrays of conducting polypyrrole (PPy) nanorods are fabricated directly on the indium-tin oxide coated glass by an electropolymerization within a porous diblock copolymer template. The nanorods are shown to have conductivity much higher than thin PPy films, due to the high degree of chain orientation, even though the separation distance for two neighboring PPy main chains is as small as 0.37 nm. The ultrahigh density arrays of conducting polymer nanorods have potential applications as sensor materials, nanoactuators, and organic photovoltaic devices.

When measuring the dielectric properties of aqueous samples, the impedance of the electrode/sample interface can limit low frequency measurements. The electrode polarization problem can be reduced by increasing the effective surface area of the electrodes. In this work, impedance spectroscopy was used to characterize and compare three different electrode surfaces that can be used to mitigate this effect: platinum black, iridium oxide, and [polypyrrole/poly(styrenesulphonate)] (PPy/PSS) conducting polymer. All three materials were directly compared with a bright platinum electrode. Equivalent circuit models were used to extract the increase in the effective surface area of the electrodes: platinum black, iridium oxide and PPy/PSS increase the effective capacitance of the electrode by factors of approximately 240, 75, and 790, respectively. The practical aspects of all electrode materials are discussed. These results suggest that iridium oxide and PPy/PSS are good alternatives to the commonly used platinum black, which is prone to mechanical damage (scratches) and is potentially toxic to cells.

In this article, we report a novel electrode of NiCo2O4 nanowire arrays (NWAs) on carbon textiles with a polypyrrole (PPy) nanosphere shell layer to enhance the pseudocapacitive performance. The merits of highly conductive PPy and short ion transport channels in ordered NiCo2O4 mesoporous nanowire arrays together with the synergistic effect between NiCo2O4 and PPy result in a high specific capacitance of 2244 F g(-1), excellent rate capability, and cycling stability in NiCo2O4/PPy electrode. Moreover, a lightweight and flexible asymmetric supercapacitor (ASC) device is successfully assembled using the hybrid NiCo2O4@PPy NWAs and activated carbon (AC) as electrodes, achieving high energy density (58.8 W h kg(-1) at 365 W kg(-1)), outstanding power density (10.2 kW kg(-1) at 28.4 W h kg(-1)) and excellent cycling stability (∼89.2% retention after 5000 cycles), as well as high flexibility. The three-dimensional coaxial architecture design opens up new opportunities to fabricate a high-performance flexible supercapacitor for future portable and wearable electronic devices.

Porous-conductive chitosan scaffolds were fabricated by blending conductive polypyrrole (PPy) particles with chitosan solution and employing an improved phase separation method. In vitro and in vivo degradation behaviors of these scaffolds were investigated. In the case of in vitro degradation, an enzymatic degradation system was employed and lysozyme was used as a working enzyme. Meanwhile, the degradation products of scaffolds, glucosamine and N-acetyl-glucosamine, were also analyzed with a HPLC method. In vivo degradation of scaffolds was performed by subcutaneously implanting these scaffolds in rat for pre-scheduled time intervals. In the both cases, the weight-loss of scaffolds was monitored during the whole degradation process for evaluating the degradation of scaffolds. The changes in conductivity of scaffolds afterin vitro or in vivo degradation were also measured using a four-point technique. It was observed that the pore parameters of scaffolds themselves could significantly influence the degradation behaviors of scaffolds but the PPy content in the scaffolds seemed not to impart its effect to the degradation of scaffolds. Degradation dynamics of scaffolds and conductivity measurements indicated that these scaffolds shown fairly different behaviors in their in vitro and in vivo degradation process. According to the results obtained from in vitro and in vivo degradation of scaffolds and based on some requirements of practical tissue engineering application, it was suggested that the PPy content in the scaffold should be slightly higher than 3 wt.% but lower than 6 wt.%.

We report the development of a generalized pH-sensitive drug delivery system that can release any charged drug preferentially at the pH range of interest. Our system is based on polypyrrole nanoparticles (PPy NPs), synthesized via a simple one-step microemulsion technique. These nanoparticles are highly monodisperse, stable in solution over the period of a month, and have good drug loading capacity (∼15 wt%). We show that PPy NPs can be tuned to release drugs at both acidic and basic pH by varying the pH, the charge of the drug, as well as by adding small amounts of charged amphiphiles. Moreover, these NPs may be delivered locally by immobilizing them in a hydrogel. Our studies show encapsulation within a calcium alginate hydrogel results in sustained release of the incorporated drug for more than 21 days. Such a nanoparticle-hydrogel composite drug delivery system is promising for treatment of long-lasting conditions such as cancer and chronic pain which require controlled, localized, and sustained drug release.

Conductive and electroactive polymers have the potential to enhance engineered cardiac tissue function. In this study, an interpenetrating network of the electrically-conductive polymer polypyrrole (PPy) was grown within a matrix of flexible polycaprolactone (PCL) and evaluated as a platform for directing the formation of functional cardiac cell sheets. PCL films were either treated with sodium hydroxide to render them more hydrophilic and enhance cell adhesion or rendered electroactive with PPy grown via chemical polymerization yielding PPy-PCL that had a resistivity of 1.0 ± 0.4 kΩ cm, which is similar to native cardiac tissue. Both PCL and PPy-PCL films supported cardiomyocyte attachment; increasing the duration of PCL pre-treatment with NaOH resulted in higher numbers of adherent cardiomyocytes per unit area, generating cell densities which were more similar to those on PPy-PCL films (1568 ± 126 cells mm(-2), 2880 ± 439 cells mm(-2), 3623 ± 456 cells mm(-2) for PCL with 0, 24, 48 h of NaOH pretreatment, respectively; 2434 ± 166 cells mm(-2) for PPy-PCL). When cardiomyocytes were cultured on the electrically-conductive PPy-PCL, more cells were observed to have peripheral localization of the gap junction protein connexin-43 (Cx43) as compared to cells on NaOH-treated PCL (60.3 ± 4.3% vs. 46.6 ± 5.7%). Cx43 gene expression remained unchanged between materials. Importantly, the velocity of calcium wave propagation was faster and calcium transient duration was shorter for cardiomyocyte monolayers on PPy-PCL (1612 ± 143 μm/s, 910 ± 63 ms) relative to cells on PCL (1129 ± 247 μm/s, 1130 ± 20 ms). In summary, PPy-PCL has demonstrated suitability as an electrically-conductive substrate for culture of cardiomyocytes, yielding enhanced functional properties; results encourage further development of conductive substrates for use in differentiation of stem cell-derived cardiomyocytes and cardiac tissue engineering applications.

UNASSIGNED

Current conductive materials for use in cardiac regeneration are limited by cytotoxicity or cost in implementation. In this manuscript, we demonstrate for the first time the application of a biocompatible, conductive polypyrrole-polycaprolactone film as a platform for culturing cardiomyocytes for cardiac regeneration. This study shows that the novel conductive film is capable of enhancing cell-cell communication through the formation of connexin-43, leading to higher velocities for calcium wave propagation and reduced calcium transient durations among cultured cardiomyocyte monolayers. Furthermore, it was demonstrated that chemical modification of polycaprolactone through alkaline-mediated hydrolysis increased overall cardiomyocyte adhesion. The results of this study provide insight into how cardiomyocytes interact with conductive substrates and will inform future research efforts to enhance the functional properties of cardiomyocytes, which is critical for their use in pharmaceutical testing and cell therapy.

The electrical stability of a novel polypyrrole (PPy)/poly(D,L-lactide) (PDLLA) composite was studied in vitro and compared with that of PPy-coated polyester fabrics. Specimens were incubated in Ringer's solution at 37 degrees C for up to 8 weeks with or without the circulation of DC current under a constant 100 mV voltage. In situ current variation with incubation time was recorded. The AC volume electrical conductivity of the specimens before and after incubation in phosphate-buffered saline was recorded using a frequency analyzer. Water absorption and weight loss were monitored metrologically. Changes in the oxidation state of incubated PPy were analyzed with X-ray photoelectron spectroscopy. The morphological changes were observed with scanning electron microscopy, and the glass transition temperature of the PDLLA was investigated using differential scanning calorimetry. The PPy/PDLLA composite in Ringer's solution sustained a relatively stable conductivity up to 8 weeks after an initial period of "conditioning." The PPy-coated fabrics experienced a rapid loss of conductivity when subjected to electrical circulation and regained part of it when disconnected. The volume conductivity of the nonincubated PPy/PDLLA membrane behaved as a typical conductor in the low-frequency range. The mechanisms involved in the various electrical behaviours of the PPy/PDLLA composite and PPy-coated fabrics are discussed. In conclusion, the PPy/PDLLA composite was able to deliver a biologically significant electrical current in a simulated biological solution for up to 8 weeks and therefore may be considered as a first-generation synthetic biodegradable bioconductor.