Stretchable and Transparent Metal Nanowire Microelectrodes for Simultaneous Electrophysiology and Optogenetics Applications

Recently developed optically transparent microelectrode technology provides a promising approach for simultaneous high-resolution electrical and optical biointerfacing with tissues in vivo and in vitro. A critically unmet need is designing high-performance stretchable platforms for conformal biointerfacing with mechanically active organs. Here, we report silver nanowire (Ag NW) stretchable transparent microelectrodes and interconnects that exhibit excellent electrical and electrochemical performance, high optical transparency, superior mechanical robustness and durability by a simple selective-patterning process. The fabrication method allows the direct integration of Ag NW networks on elastomeric substrates. The resulting Ag NW interface exhibits a low sheet resistance (Rsh) of 1.52–4.35 Ω sq−1, an advantageous normalized electrochemical impedance of 3.78–6.04 Ω cm2, a high optical transparency of 61.3–80.5% at 550 nm and a stretchability of 40%. The microelectrode arrays (MEAs) fabricated with this approach exhibit uniform electrochemical performance across all channels. Studies on mice demonstrate that both pristine and stretched Ag NW microelectrodes can achieve high-fidelity electrophysiological monitoring of cardiac activity with/without co-localized optogenetic pacing. Together, these results pave the way for developing stretchable and transparent metal nanowire networks for high-resolution opto-electric biointerfacing with mechanically active organs, such as the heart.

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From local to global matrix organization by fibroblasts: a 4D laser-assisted bioprinting approach

Biofabrication ◽

10.1088/1758-5090/ac40ed ◽

2021 ◽

Author(s):

Camille Douillet ◽

Marc Nicodeme ◽

Loïc Hermant ◽

Vanessa Bergeron ◽

Fabien Guillemot ◽

...

Keyword(s):

High Resolution ◽

Soft Tissue ◽

Dynamic Properties ◽

Unmet Need ◽

Specific Pattern ◽

Matrix Remodeling ◽

Collagen Gels ◽

Lattice Contraction

Abstract Fibroblasts and myofibroblasts play a central role in skin homeostasis through dermal organization and maintenance. Nonetheless, the dynamic interactions between (myo)fibroblasts and the extracellular matrix (ECM) remain poorly exploited in skin repair strategies. Indeed, there is still an unmet need for soft tissue models allowing to study the spatial-temporal remodeling properties of (myo)fibroblasts. In vivo, wound healing studies in animals are limited by species specificity. In vitro, most models rely on collagen gels reorganized by randomly distributed fibroblasts. But biofabrication technologies have significantly evolved over the past ten years. High-resolution bioprinting now allows to investigate various cellular micropatterns and the emergent tissue organizations over time. In order to harness the full dynamic properties of cells and active biomaterials, it is essential to consider “time” as the 4th dimension in soft tissue design. Following this 4D bioprinting approach, we aimed to develop a novel model that could replicate fibroblast dynamic remodeling in vitro. For this purpose, (myo)fibroblasts were patterned on collagen gels with laser-assisted bioprinting (LAB) to study the generated matrix deformations and reorganizations. First, distinct populations, mainly composed of fibroblasts or myofibroblasts, were established in vitro to account for the variety of fibroblastic remodeling properties. Then, LAB was used to organize both populations on collagen gels in even isotropic patterns with high resolution, high density and high viability. With maturation, bioprinted patterns of fibroblasts and myofibroblasts reorganized into dispersed or aggregated cells, respectively. Stress-release contraction assays revealed that these phenotype-specific pattern maturations were associated with distinct lattice tension states. The two populations were then patterned in anisotropic rows in order to direct the cell-generated deformations and to orient global matrix remodeling. Only maturation of anisotropic fibroblast patterns, but not myofibroblasts, resulted in collagen anisotropic reorganizations both at tissue-scale, with lattice contraction, and at microscale, with embedded microbead displacements. Following a 4D bioprinting approach, LAB patterning enabled to elicit and orient the dynamic matrix remodeling mechanisms of distinct fibroblastic populations and organizations on collagen. For future studies, this method provides a new versatile tool to investigate in vitro dermal organizations and properties, processes of remodeling in healing, and new treatment opportunities.

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A Direct Comparison of Glassy Carbon and PEDOT-PSS Electrodes for High Charge Injection and Low Impedance Neural Interfaces

Advances in Science and Technology ◽

10.4028/www.scientific.net/ast.102.68 ◽

2016 ◽

Vol 102 ◽

pp. 68-76 ◽

Cited By ~ 2

Author(s):

Maria Vomero ◽

Elisa Castagnola ◽

Emma Maggiolini ◽

Francesca Ciarpella ◽

Irene Rembado ◽

...

Keyword(s):

Electrochemical Performance ◽

Glassy Carbon ◽

Cultured Cells ◽

Electrochemical Impedance ◽

Neural Interfaces ◽

Somatosensory Stimulation ◽

Brain Surface ◽

First Time

For neural applications, materials able to interface with the brain without harming it while recording high-fidelity signals over long-term implants are still sought after. Glassy Carbon (GC) and Poly (3,4-ethylenedioxythiophene)-poly (styrenesulfonate) (PEDOT-PSS) have proved to be promising materials for neural interfaces as they show – compared to conventional metal electrodes - higher conductivity, better electrochemical stability, very good mechanical properties and therefore seem to be very promising for in vivo applications. We present here, for the first time, a direct comparison between GC and PEDOT-PSS microelectrodes in terms of biocompatibility, electrical and electrochemical properties as well as in vivo recording capabilities, using electrocorticography microelectrode arrays located on flexible polyimide substrate. The GC microelectrodes were fabricated using a traditional negative lithography processes followed by pyrolysis. PEDOT-PSS was selectively electrodeposited on the desired electrodes. Electrochemical performance of the two materials was evaluated through electrochemical impedance spectroscopy and cyclic voltammetry. Biocompatibility was assessed through in-vitro studies evaluating cultured cells viability. The in vivo performance of the GC and PEDOT-PSS electrodes was directly compared by simultaneously recording neuronal activity during somatosensory stimulation in Long-Evans rats. We found that both GC and PEDOT-PSS electrodes outperform metals in terms of electrochemical performance and allow to obtain excellent recordings of somatosensory evoked potentials from the rat brain surface. Furthermore, we found that both GC and PEDOT-PSS substrates are highly biocompatible, confirming that they are safe for neural interface applications.

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Comparison of the In Vitro and In Vivo Electrochemical Performance of Bionic Electrodes

Micromachines ◽

10.3390/mi13010103 ◽

2022 ◽

Vol 13 (1) ◽

pp. 103

Author(s):

Alexander R. Harris ◽

Carrie Newbold ◽

Dimitra Stathopoulos ◽

Paul Carter ◽

Robert Cowan ◽

...

Keyword(s):

Electrochemical Performance ◽

Electrochemical Impedance ◽

Fibrous Tissue ◽

In Vitro Testing ◽

Experimental Conditions ◽

Electrode Implantation ◽

Electrochemical Response ◽

The Impact

The electrochemical performance of platinum electrodes was assessed in vitro and in vivo to determine the impact of electrode implantation and the relevance of in vitro testing in predicting in vivo behaviour. A significant change in electrochemical response was seen after electrode polarisation. As a result, initial in vitro measurements were poor predictors of subsequent measurements performed in vitro or in vivo. Charge storage capacity and charge density measurements from initial voltammetric measurements were not correlated with subsequent measurements. Electrode implantation also affected the electrochemical impedance. The typically reported impedance at 1 kHz was a very poor predictor of electrode performance. Lower frequencies were significantly more dependent on electrode properties, while higher frequencies were dependent on solution properties. Stronger correlations in impedance at low frequencies were seen between in vitro and in vivo measurements after electrode activation had occurred. Implanting the electrode increased the resistance of the electrochemical circuit, with bone having a higher resistivity than soft tissue. In contrast, protein fouling and fibrous tissue formation had a minimal impact on electrochemical response. In vivo electrochemical measurements also typically use a quasi-reference electrode, may operate in a 2-electrode system, and suffer from uncompensated resistance. The impact of these experimental conditions on electrochemical performance and the relevance of in vitro electrode assessment is discussed. Recommended in vitro testing protocols for assessing bionic electrodes are presented.

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Polymorphisms in Plasmodium falciparum dihydropteroate synthetase and dihydrofolate reductase genes in Nigerian children with uncomplicated malaria using high-resolution melting technique

Scientific Reports ◽

10.1038/s41598-020-80017-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Adeyemi T. Kayode ◽

Fehintola V. Ajogbasile ◽

Kazeem Akano ◽

Jessica N. Uwanibe ◽

Paul E. Oluniyi ◽

...

Keyword(s):

High Resolution ◽

Dihydrofolate Reductase ◽

Uncomplicated Malaria ◽

High Resolution Melting ◽

Intermittent Preventive Treatment ◽

Preventive Treatment ◽

Triple Mutant ◽

Seasonal Malaria Chemoprevention

AbstractIn 2005, the Nigerian Federal Ministry of Health revised the treatment policy for uncomplicated malaria with the introduction of artemisinin-based combination therapies (ACTs). This policy change discouraged the use of Sulphadoxine-pyrimethamine (SP) as the second-line treatment of uncomplicated falciparum malaria. However, SP is used as an intermittent preventive treatment of malaria in pregnancy (IPTp) and seasonal malaria chemoprevention (SMC) in children aged 3–59 months. There have been increasing reports of SP resistance especially in the non-pregnant population in Nigeria, thus, the need to continually monitor the efficacy of SP as IPTp and SMC by estimating polymorphisms in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes associated with SP resistance. The high resolution-melting (HRM) assay was used to investigate polymorphisms in codons 51, 59, 108 and 164 of the dhfr gene and codons 437, 540, 581 and 613 of the dhps gene. DNA was extracted from 271 dried bloodspot filter paper samples obtained from children (< 5 years old) with uncomplicated malaria. The dhfr triple mutant I51R59N108, dhps double mutant G437G581 and quadruple dhfr I51R59N108 + dhps G437 mutant haplotypes were observed in 80.8%, 13.7% and 52.8% parasites, respectively. Although the quintuple dhfr I51R59N108 + dhps G437E540 and sextuple dhfr I51R59N108 + dhps G437E540G581 mutant haplotypes linked with in-vivo and in-vitro SP resistance were not detected, constant surveillance of these haplotypes should be done in the country to detect any change in prevalence.

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Continuous Delivery of Stromal Cell-Derived Factor-1 from Alginate Scaffolds Accelerates Wound Healing

Cell Transplantation ◽

10.3727/096368909x481782 ◽

2010 ◽

Vol 19 (4) ◽

pp. 399-408 ◽

Cited By ~ 100

Author(s):

Sina Y. Rabbany ◽

Joseph Pastore ◽

Masaya Yamamoto ◽

Tim Miller ◽

Shahin Rafii ◽

...

Keyword(s):

Wound Healing ◽

Stromal Cell ◽

Wound Closure ◽

Tissue Injury ◽

Unmet Need ◽

Novel Therapy ◽

Yorkshire Pigs ◽

Stromal Cell Derived Factor

Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics. Our study utilized an alginate hydrogel patch to deliver stromal cell-derived factor-1 (SDF-1), a naturally occurring chemokine that is rapidly overexpressed in response to tissue injury, to assess the potential effects SDF-1 therapy on wound closure rates and scar formation. Alginate patches were loaded with either purified recombinant human SDF-1 protein or plasmid expressing SDF-1 and the kinetics of SDF-1 release were measured both in vitro and in vivo in mice. Our studies demonstrate that although SDF-1 plasmid- and protein-loaded patches were able to release therapeutic product over hours to days, SDF-1 protein was released faster (in vivo Kd 0.55 days) than SDF-1 plasmid (in vivo Kd 3.67 days). We hypothesized that chronic SDF-1 delivery would be more effective in accelerating the rate of dermal wound closure in Yorkshire pigs with acute surgical wounds, a model that closely mimics human wound healing. Wounds treated with SDF-1 protein ( n = 10) and plasmid ( n = 6) loaded patches healed faster than sham ( n = 4) or control ( n = 4). At day 9, SDF-1-treated wounds significantly accelerated wound closure (55.0 ± 14.3% healed) compared to nontreated controls (8.2 ± 6.0%, p < 0.05). Furthermore, 38% of SDF-1-treated wounds were fully healed at day 9 (vs. none in controls) with very little evidence of scarring. These data suggest that patch-mediated SDF-1 delivery may ultimately provide a novel therapy for accelerating healing and reducing scarring in clinical wounds.

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Click Activated Protodrugs Against Cancer Increase the Therapeutic Potential of Chemotherapy through Local Capture and Activation

10.26434/chemrxiv.13087715 ◽

2020 ◽

Author(s):

Kui Wu ◽

Nathan Yee ◽

Sangeetha Srinivasan ◽

Amir Mahmoodi ◽

Michael Zakharian ◽

...

Keyword(s):

Therapeutic Potential ◽

Unmet Need ◽

Sodium Hyaluronate ◽

Maximum Tolerated Dose ◽

The Body ◽

In Vivo Studies ◽

Tumor Biomarker ◽

Tumor Site

<div> <div> <div> <p>A desired goal of targeted cancer treatments is to achieve high tumor specificity with minimal side effects. Despite recent advances, this remains difficult to achieve in practice as most approaches rely on biomarkers or physiological differences between malignant and healthy tissue, and thus benefit only a subset of patients in need of treatment. To address this unmet need, we introduced a Click Activated Protodrugs Against Cancer (CAPAC) platform that enables targeted activation of drugs at a specific site in the body, i.e., a tumor. In contrast to antibodies (mAbs, ADCs) and other targeted approaches, the mechanism of action is based on in vivo click chemistry, and is thus independent of tumor biomarker expression or factors such as enzymatic activity, pH, or oxygen levels. The platform consists of a tetrazine-modified sodium hyaluronate-based biopolymer injected at a tumor site, followed by one or more doses of a trans-cyclooctene (TCO)- modified cytotoxic protodrug with attenuated activity administered systemically. The protodrug is captured locally by the biopolymer through an inverse electron-demand Diels-Alder reaction between tetrazine and TCO, followed by conversion to the active drug directly at the tumor site, thereby overcoming the systemic limitations of conventional chemotherapy or the need for specific biomarkers of traditional targeted therapy. Here, TCO-modified protodrugs of four prominent cytotoxics (doxorubicin, paclitaxel, etoposide and gemcitabine) are used, highlighting the modularity of the CAPAC platform. In vitro evaluation of cytotoxicity, solubility, stability and activation rendered the protodrug of doxorubicin, SQP33, as the most promising candidate for in vivo studies. Studies in rodents show that a single injection of the tetrazine-modified biopolymer, SQL70, efficiently captures SQP33 protodrug doses given at 10.8-times the maximum tolerated dose of conventional doxorubicin with greatly reduced systemic toxicity. </p> </div> </div> </div>

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Evaluation of NV556, a Novel Cyclophilin Inhibitor, as a Potential Antifibrotic Compound for Liver Fibrosis

Cells ◽

10.3390/cells8111409 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1409 ◽

Cited By ~ 1

Author(s):

Sonia Simón Serrano ◽

Alvar Grönberg ◽

Lisa Longato ◽

Krista Rombouts ◽

Joseph Kuo ◽

...

Keyword(s):

Liver Fibrosis ◽

Stellate Cell ◽

Unmet Need ◽

Potential Candidate ◽

In Vivo Models ◽

Fibrotic Process ◽

Increased Risk ◽

Cyclophilin Inhibitor

Hepatic fibrosis can result as a pathological response to nonalcoholic steatohepatitis (NASH). Cirrhosis, the late stage of fibrosis, has been linked to poor survival and an increased risk of developing hepatocellular carcinoma, with limited treatment options available. Therefore, there is an unmet need for novel effective antifibrotic compounds. Cyclophilins are peptidyl-prolyl cis-trans isomerases that facilitate protein folding and conformational changes affecting the function of the targeted proteins. Due to their activity, cyclophilins have been presented as key factors in several stages of the fibrotic process. In this study, we investigated the antifibrotic effects of NV556, a novel potent sanglifehrin-based cyclophilin inhibitor, in vitro and in vivo. NV556 potential antifibrotic effect was evaluated in two well-established animal models of NASH, STAM, and methionine-choline-deficient (MCD) mice, as well as in an in vitro 3D human liver ECM culture of LX2 cells, a human hepatic stellate cell line. We demonstrate that NV556 decreased liver fibrosis in both STAM and MCD in vivo models and decreased collagen production in TGFβ1-activated hepatic stellate cells in vitro. Taken together, these results present NV556 as a potential candidate for the treatment of liver fibrosis.

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In vitro and in vivo metabolism of 3-quinuclidinyl benzilate by high-resolution mass spectrometry

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2020.113519 ◽

2020 ◽

Vol 190 ◽

pp. 113519

Author(s):

Martin Uher ◽

Martin Mžik ◽

Jana Žďárová Karasová ◽

David Herman ◽

Lenka Čechová ◽

...

Keyword(s):

Mass Spectrometry ◽

High Resolution ◽

High Resolution Mass Spectrometry ◽

In Vivo Metabolism ◽

High Resolution Mass ◽

Resolution Mass ◽

Quinuclidinyl Benzilate

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Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant Staphylococcus aureus

Pharmaceutics ◽

10.3390/pharmaceutics12111093 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1093

Author(s):

Daniel Hassan ◽

Calvin A. Omolo ◽

Victoria Oluwaseun Fasiku ◽

Ahmed A Elrashedy ◽

Chunderika Mocktar ◽

...

Keyword(s):

Staphylococcus Aureus ◽

High Resolution ◽

Antimicrobial Resistance ◽

Methicillin Resistant Staphylococcus Aureus ◽

Human Beings ◽

Ph Responsive ◽

Methicillin Resistant ◽

13C Nuclear Magnetic Resonance

Globally, human beings continue to be at high risk of infectious diseases caused by methicillin-resistant Staphylococcus aureus (MRSA); and current treatments are being depleted due to antimicrobial resistance. Therefore, the synthesis and formulation of novel materials is essential for combating antimicrobial resistance. The study aimed to synthesize a quaternary bicephalic surfactant (StBAclm) and thereof to formulate pH-responsive vancomycin (VCM)-loaded quatsomes to enhance the activity of the antibiotic against MRSA. The surfactant structure was confirmed using 1H, 13C nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and high-resolution mass spectrometry (HRMS). The quatsomes were prepared using a sonication/dispersion method and were characterized using various in vitro, in vivo, and in silico techniques. The in vitro cell biocompatibility studies of the surfactant and pH-responsive vancomycin-loaded quatsomes (VCM-StBAclm-Qt1) revealed that they are biosafe. The prepared quatsomes had a mean hydrodynamic diameter (MHD), polydispersity index (PDI), and drug encapsulation efficiency (DEE) of 122.9 ± 3.78 nm, 0.169 ± 0.02 mV, and 52.22 ± 8.4%, respectively, with surface charge switching from negative to positive at pH 7.4 and pH 6.0, respectively. High-resolution transmission electron microscopy (HR-TEM) characterization of the quatsomes showed spherical vesicles with MHD similar to the one obtained from the zeta-sizer. The in vitro drug release of VCM from the quatsomes was faster at pH 6.0 compared to pH 7.4. The minimum inhibitory concentration (MIC) of the drug loaded quatsomes against MRSA was 32-fold and 8-fold lower at pH 6.0 and pH 7.4, respectively, compared to bare VCM, demonstrating the pH-responsiveness of the quatsomes and the enhanced activity of VCM at acidic pH. The drug-loaded quatsomes demonstrated higher electrical conductivity and a decrease in protein and deoxyribonucleic acid (DNA) concentrations as compared to the bare drug. This confirmed greater MRSA membrane damage, compared to treatment with bare VCM. The flow cytometry study showed that the drug-loaded quatsomes had a similar bactericidal killing effect on MRSA despite a lower (8-fold) VCM concentration when compared to the bare VCM. Fluorescence microscopy revealed the ability of the drug-loaded quatsomes to eradicate MRSA biofilms. The in vivo studies in a skin infection mice model showed that groups treated with VCM-loaded quatsomes had a 13-fold decrease in MRSA CFUs when compared to the bare VCM treated groups. This study confirmed the potential of pH-responsive VCM-StBAclm quatsomes as an effective delivery system for targeted delivery and for enhancing the activity of antibiotics.

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