Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 28
Filter
Add more filters










Publication year range
1.
J Health Commun ; 28(sup2): 49-60, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-38146161

ABSTRACT

Misinformation can decrease public confidence in vaccines, and reduce vaccination intent and uptake. One strategy for countering these negative impacts comes from inoculation theory. Similar to biological vaccination, inoculation theory posits that exposure to a weakened form of misinformation can develop cognitive immunity, reducing the likelihood of being misled. Online games offer an interactive, technology-driven, and scalable solution using an active form of inoculation that engages and incentivizes players to build resilience against misinformation. We document the development of the critical thinking game Cranky Uncle Vaccine. The game applies research findings from inoculation theory, critical thinking, humor in science communication, and serious games. The game content was iterated through a series of co-design workshops in Kampala (Uganda), Kitale (Kenya), and Kigali (Rwanda). Workshop participants offered feedback on cartoon character design, gameplay experience, and the game's content, helping to make the game more culturally relevant and avoid unintended consequences in East African countries. Our co-design methodology offers an approach for further adaptation of the Cranky Uncle Vaccine game to other regions, as well as a template for developing locally relevant interventions to counter future infodemics.


Subject(s)
Communication , Vaccines , Humans , Kenya , Uganda , Rwanda
2.
ACS Nano ; 17(18): 18470-18480, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37669408

ABSTRACT

Self-assembling virus-like particles (VLPs) can tolerate a wide degree of genetic and chemical manipulation to their capsid protein to display a foreign molecule polyvalently. We previously reported the successful incorporation of foreign peptide sequences in the junction loop and onto the C-terminus of PP7 dimer VLPs, as these regions are accessible for surface display on assembled capsids. Here, we report the implementation of a library-based approach to test the assembly tolerance of PP7 dimer capsid proteins to insertions or terminal extensions of randomized 15-mer peptide sequences. By performing two iterative rounds of assembly-based selection, we evaluated the degree of favorability of all 20 amino acids at each of the 15 randomized positions. Deep sequencing analysis revealed a distinct preference for the inclusion of hydrophilic peptides and negatively charged amino acids (Asp and Glu) and the exclusion of positively charged peptides and bulky and hydrophobic amino acid residues (Trp, Phe, Tyr, and Cys). Within the libraries tested here, we identified 4000 to 22,000 unique 15-mer peptide sequences that can successfully be displayed on the surface of the PP7 dimer capsid. Overall, the use of small initial libraries consisting of no more than a few million members yielded a significantly larger number of unique and assembly-competent VLP sequences than have been previously characterized for this class of nucleoprotein particle.


Subject(s)
Amino Acids , Peptides , Amino Acid Sequence , Capsid , Capsid Proteins/genetics , Polymers
3.
PLoS One ; 16(5): e0251412, 2021.
Article in English | MEDLINE | ID: mdl-33979385

ABSTRACT

Hearing depends on the transduction of sounds into neural signals by the inner hair cells of the cochlea. Cochleae also have outer hair cells with unique electromotile properties that increase auditory sensitivity, but they are particularly susceptible to damage by intense noise exposure, ototoxic drugs, and aging. Although the outer hair cells have synapses on afferent neurons that project to the brain, the function of this neuronal circuit is unclear. Here, we created a novel mouse allele that inserts a fluorescent reporter at the C1ql1 locus which revealed gene expression in the outer hair cells and allowed creation of outer hair cell-specific C1ql1 knockout mice. We found that C1ql1 expression in outer hair cells corresponds to areas with the most sensitive frequencies of the mouse audiogram, and that it has an unexpected adolescence-onset developmental timing. No expression was observed in the inner hair cells. Since C1QL1 in the brain is made by neurons, transported anterogradely in axons, and functions in the synaptic cleft, C1QL1 may serve a similar function at the outer hair cell afferent synapse. Histological analyses revealed that C1ql1 conditional knockout cochleae may have reduced outer hair cell afferent synapse maintenance. However, auditory behavioral and physiological assays did not reveal a compelling phenotype. Nonetheless, this study identifies a potentially useful gene expressed in the cochlea and opens the door for future studies aimed at elucidating the function of C1QL1 and the function of the outer hair cell and its afferent neurons.


Subject(s)
Cochlea/metabolism , Complement C1q/metabolism , Hair Cells, Auditory, Outer/metabolism , Alleles , Animals , Complement C1q/genetics , Mice , Mice, Knockout , Synapses/metabolism
4.
Emerg Med Australas ; 33(3): 534-540, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33586331

ABSTRACT

OBJECTIVE: To assess changes in presentations to EDs during the COVID-19 pandemic lockdown in the Southern Region of New Zealand. METHODS: We conducted a retrospective audit of patients attending EDs in the Southern District Health Board (SDHB), from 1 March to 13 May 2020. We made comparisons with attendances during the same period in 2019. The 2020 study period included 'pre-lockdown' (1 March-25 March), 'level 4 (strict) lockdown' (26 March-27 April) and 'level 3 (eased) lockdown' (28 April-13 May). RESULTS: Patient volumes reduced in all SDHB EDs during levels 4 and 3, mostly representing a loss of low acuity patients (Australasian Triage Scale 3, 4 and 5), although high-acuity presentations also declined. Average patient age increased by 5 years; however, the proportions of sexes and ethnicities did not change. Presentations of cerebrovascular accidents and appendicitis did not change significantly. Trauma, mental health, acute coronary syndrome and infectious respiratory presentations decreased significantly during level 4, and infectious respiratory presentations decreased further in level 3. CONCLUSIONS: Within the SDHB, patient volumes reduced during levels 4 and 3 of our lockdown, with reduced low-acuity presentations. High-acuity patient numbers also declined. Trauma, mental health, alcohol-related, infectious respiratory and acute coronary syndrome presentations declined while cerebrovascular accident and appendicitis numbers showed little to no change.

5.
FASEB J ; 35(1): e21194, 2021 01.
Article in English | MEDLINE | ID: mdl-33337553

ABSTRACT

Synapses are the fundamental structural unit by which neurons communicate. An orchestra of proteins regulates diverse synaptic functions, including synapse formation, maintenance, and elimination-synapse homeostasis. Some proteins of the larger C1q super-family are synaptic organizers involved in crucial neuronal processes in various brain regions. C1Q-like (C1QL) proteins bind to the adhesion G protein-coupled receptor B3 (ADGRB3) and act at synapses in a subset of circuits. To investigate the hypothesis that the secreted C1QL proteins mediate tripartite trans-synaptic adhesion complexes, we conducted an in vivo interactome study and identified new binding candidates. We demonstrate that C1QL3 mediates a novel cell-cell adhesion complex involving ADGRB3 and two neuronal pentraxins, NPTX1 and NPTXR. Analysis of single-cell RNA-Seq data from the cerebral cortex shows that C1ql3, Nptx1, and Nptxr are highly co-expressed in the same excitatory neurons. Thus, our results suggest the possibility that in vivo the three co-expressed proteins are presynaptically secreted and form a complex capable of binding to postsynaptically localized ADGRB3, thereby creating a novel trans-synaptic adhesion complex. Identifying new binding partners for C1QL proteins and deciphering their underlying molecular principles will accelerate our understanding of their role in synapse organization.


Subject(s)
C-Reactive Protein/metabolism , Complement C1q/metabolism , Membrane Proteins/metabolism , Multiprotein Complexes/metabolism , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Synapses/metabolism , Animals , C-Reactive Protein/genetics , Cell Adhesion/genetics , Complement C1q/genetics , Male , Membrane Proteins/genetics , Mice , Multiprotein Complexes/genetics , Nerve Tissue Proteins/genetics , Synapses/genetics
6.
Acta Biomater ; 94: 585-596, 2019 08.
Article in English | MEDLINE | ID: mdl-31129362

ABSTRACT

An artificial cornea or keratoprosthesis requires high mechanical strength, good biocompatibility, and sufficient wear and corrosion resistance to withstand the hostile environment. We report a reduced graphene oxide-reinforced titania-based composite for this application. Graphene oxide nanoparticles (GO) and liquid crystalline graphene oxide (LCGO) were the graphene precursors and mixed with titanium dioxide (TiO2) powder. The composites reinforced with reduced GO or LCGO were produced through spark plasma sintering (SPS). The mechanical properties (Young's modulus and hardness), wear behaviour and corrosion resistance were studied using nanoindentation, anoidic polarization, long-term corrosion assay in artificial tear fluid and tribology assay in corroboration with atomic force microscopy and scanning electron microscopy. Biocompatibility was assessed by human corneal stromal cell attachment, survival and proliferation, and DNA damages. Sintered composites were implanted into rabbit corneas to assess for in vivo stability and host tissue responses. We showed that reduced graphene/TiO2 hybrids were safe and biocompatible. In particular, the 1% reduced LCGO/TiO2 (1rLCGO/TiO2) composite was mechanically strong, chemically stable, and showed better wear and corrosion resistance than pure titania and other combinations of graphene-reinforced titania. Hence the 1rLCGO/ TiO2 bioceramics can be a potential skirt biomaterial for keratoprosthesis to treat end-stage corneal blindness. STATEMENT OF SIGNIFICANCE: The osteo-odonto-keratoprosthesis (OOKP) is an artificial cornea procedure used to restore vision in end-stage corneal diseases, however it is contraindicated in young subjects, patients with advanced imflammatory diseases and posterior segment complications. Hence, there is a need of an improved keratoprosthesisskirt material with high mechanical and chemical stability, wear resistance and tissue integration ability. Our study characterized a reduced graphene oxide-reinforced titania-based biomaterial, which demonstrated strong mechanical strength, wear and corrosion resistance, and was safe and biocompatible to human corneal stromal cells. In vivo implantation to rabbit corneas did not cause any immune and inflammation outcomes. In conclusion, this invention is a potential keratoprosthesis skirt biomaterial to withstand the hostile environment in treating end-stage corneal blindness.


Subject(s)
Cornea , Corneal Diseases , Graphite/chemistry , Implants, Experimental , Materials Testing , Titanium/chemistry , Animals , Cornea/metabolism , Cornea/pathology , Corneal Diseases/metabolism , Corneal Diseases/pathology , Corneal Diseases/surgery , Humans , Rabbits , Stromal Cells/metabolism , Stromal Cells/pathology
7.
J Biomed Mater Res A ; 105(12): 3502-3513, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28869708

ABSTRACT

The manufacture of mechanically strong and biocompatible titania (TiO2 ) materials is of vital importance for their application as corneal implant skirts. This study was aimed at optimizing the selection of raw powder and sintering conditions for TiO2 ceramics. TiO2 compacts were synthesized from five raw powders, denoted as Altair, Inframat, Alfa, Materion, and Amperit, respectively, by spark plasma sintering using different sintering parameters. The XRD and Raman results confirmed that the anatase TiO2 phase in the Inframat powder had converted completely to rutile TiO2 phase after sintering at 900°C and above. The nanoindentation results indicated that among the five types of TiO2 samples sintered at 1100°C, the Inframat pellets possessed the highest Young's modulus and hardness. Additionally, when Materion samples were employed to study the effects of SPS parameters, a higher sintering temperature in the range of 1100-1300°C decreased the mechanical properties of sintered pellets probably due to the generation of more structural defects. Culture of human corneal stromal fibroblasts on the sintered sample surfaces showed that comparably high cell viability and proliferation were observed on all TiO2 samples except Amperit compared to positive control. Furthermore, cells cultured on Inframat TiO2 sintered in the temperature range of 900-1300°C exhibited viability and formation of focal adhesion complex similar to those on control, and those prepared at 1100°C had significantly higher cell proliferation indices than control. In conclusion, Inframat TiO2 consolidated at 1100°C by SPS was the best formulation for the preparation of mechanically strong and biocompatible Keratoprosthesis skirt. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3502-3513, 2017.


Subject(s)
Biocompatible Materials/chemistry , Cornea/cytology , Titanium/chemistry , Cell Proliferation , Cell Survival , Cells, Cultured , Ceramics/chemistry , Elastic Modulus , Female , Hardness , Humans , Materials Testing , Middle Aged , Prostheses and Implants
8.
Biomed Mater ; 11(6): 065006, 2016 10 27.
Article in English | MEDLINE | ID: mdl-27786167

ABSTRACT

It is challenging to obtain dense 45S5 Bioglass® (45S5) with controlled crystallinity and satisfactory mechanical properties by conventional sintering processes due to its fast crystallization above the first glass transition temperature. Spark plasma sintering (SPS) has stood out in this respect by virtue of its capability to provide fast heating and densification rates. However, there have been insufficient investigations into the in vitro biological properties of 45S5 compacts obtained by SPS. In this study, we report the fabrication of fully densified 45S5 pellets in the temperature range of 500 °C-600 °C through a rapid SPS process (sintering for 3 min) as well as the assessment of the influence of sintering temperature and aqueous aging on the biological properties of sintered pellets with L929 and MG63 cells. The cell culture results showed that both extended ageing and a lower SPS temperature in the 500-600 °C range could generally lead to faster cell proliferation and higher cell viability. The former was possibly caused by the slower alkalization of the media during cell culture, and the latter may have resulted from the release of more Ca and Si ions. The pellet sintered at 550 °C without aqueous aging led to the highest ALP activity in MG63 cells, which may be attributed to the high interfacial pH at the pellet surface and the leaching of more Si ions. Therefore, dense 45S5 compacts with mild crystallinity consolidated by SPS at 550 °C is a promising candidate for orthopedic implants in loading bearing applications.


Subject(s)
Ceramics/chemistry , Glass/chemistry , Materials Testing , Surface Properties , Tissue Engineering/methods , Aging , Animals , Biocompatible Materials/chemistry , Calcium/chemistry , Cell Line , Cell Proliferation , Cell Survival , Crystallization/methods , Durapatite/chemistry , Humans , Hydrogen-Ion Concentration , Mice , Orthopedics , Osteoblasts/metabolism , Powders , Silicon/chemistry , Temperature , X-Ray Diffraction
9.
Mater Sci Eng C Mater Biol Appl ; 69: 956-66, 2016 Dec 01.
Article in English | MEDLINE | ID: mdl-27612791

ABSTRACT

Transparent bioceramics have attracted a large amount of research interest as they facilitate direct observation of biointerfacial reactions. Thus far, attempts to achieve transparent hydroxyapatite have been focused on augmenting the sintering pressure and/or extending the sintering duration. This study aims at fabricating transparent HA using a direct and fast spark plasma sintering process with appropriate starting powder and moderate sintering pressure. Three types of raw powder, namely micro-spheres, nano-rods and nano-spheres, were sintered to investigate the optical and biological properties of the compacted pellets. It was found that in terms of transparency, the micro-sphere pellet sintered at 1000°C stood out with an in-line transmittance as high as 84% achieved at 1300nm for a 2mm thick sample. In addition, pellets fabricated from micro-spheres demonstrated the highest cell viability in in vitro biological tests with L929 cells. Living cells cultured on a transparent micro-sphere pellet could be directly and clearly observed by light microscopy. It is thus concluded that the micro-sphere powder is the most desirable raw material to manufacture transparent hydroxyapatite because it could enable dense pellets with notably high transparency and outstanding in vitro biocompatibility to be readily obtained.


Subject(s)
Durapatite/pharmacology , Materials Testing/methods , Nanoparticles/chemistry , Optical Phenomena , Animals , Cell Count , Cell Differentiation/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Durapatite/chemistry , Humans , Mice , Nanoparticles/ultrastructure , Optical Imaging , Photoelectron Spectroscopy , Scattering, Radiation , Temperature , X-Ray Diffraction
10.
Acta Biomater ; 45: 328-339, 2016 11.
Article in English | MEDLINE | ID: mdl-27554016

ABSTRACT

Neuromuscular junctions (NMJ) are specialized synapses that link motor neurons with muscle fibers. These sites are fundamental to human muscle activity, controlling swallowing and breathing amongst many other vital functions. Study of this synapse formation is an essential area in neuroscience; the understanding of how neurons interact and control their targets during development and regeneration are fundamental questions. Existing data reveals that during initial stages of development neurons target and form synapses driven by biophysical and biochemical cues, and during later stages they require electrical activity to develop their functional interactions. The aim of this study was to investigate the effect of exogenous electrical stimulation (ES) electrodes directly in contact with cells, on the number and size of acetylcholine receptor (AChR) clusters available for NMJ formation. We used a novel in vitro model that utilizes a flexible electrical stimulation system and allows the systematic testing of several stimulation parameters simultaneously as well as the use of alternative electrode materials such as conductive polymers to deliver the stimulation. Functionality of NMJs under our co-culture conditions was demonstrated by monitoring changes in the responses of primary myoblasts to chemical stimulants that specifically target neuronal signaling. Our results suggest that biphasic electrical stimulation at 250Hz, 100µs pulse width and current density of 1mA/cm2 for 8h, applied via either gold-coated mylar or the conductive polymer PPy, significantly increased the number and size of AChRs clusters available for NMJ formation. This study supports the beneficial use of direct electrical stimulation as a strategic therapy for neuromuscular disorders. STATEMENT OF SIGNIFICANCE: The beneficial effects of electrical stimulation (ES) on human cells in vitro and in vivo have long been known. Although the effects of stimulation are clear and the therapeutic benefits are known, no uniform parameters exist with regard to the duration, frequency and amplitude of the ES. To this end, we are answering several important questions on the parameters for ES of nerve and muscle monocultures and co-cultures by probing the effects on the enhancement of acetylcholine receptors (AChR) clustering available for neuromuscular junction formation using a conductive platform. This work opens the possibility to combine electrical stimulus delivered via conductive polymer substrates, from which biomolecules could also be delivered, providing opportunities to further enhance the therapeutic effect.


Subject(s)
Neuromuscular Junction/metabolism , Receptors, Cholinergic/metabolism , Animals , Calcium/metabolism , Cell Line , Coculture Techniques , Electric Stimulation , Electrodes , Materials Testing , Mice, Inbred C57BL , Microscopy, Atomic Force , Muscles/metabolism , Nerve Tissue/metabolism
11.
Biofabrication ; 8(2): 025013, 2016 May 23.
Article in English | MEDLINE | ID: mdl-27213861

ABSTRACT

Tissue engineering scaffolds for nerve regeneration, or artificial nerve conduits, are particularly challenging due to the high level of complexity the structure of the nerve presents. The list of requirements for artificial nerve conduits is long and includes the ability to physically guide nerve growth using physical and chemical cues as well as electrical stimulation. Combining these characteristics into a conduit, while maintaining biocompatibility and biodegradability, has not been satisfactorily achieved by currently employed fabrication techniques. Here we present a method combining pultrusion and wet-spinning techniques facilitating incorporation of pre-formed filaments into ionically crosslinkable hydrogels. This new biofabrication technique allows the incorporation of conducting or drug-laden filaments, controlled guidance channels and living cells into hydrogels, creating new improved conduit designs.


Subject(s)
Hydrogels/chemistry , Neurons/cytology , Tissue Engineering/instrumentation , Tissue Scaffolds/chemistry , Alginates/chemistry , Animals , Biocompatible Materials/chemistry , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Nerve Regeneration , PC12 Cells , Rats
12.
ACS Appl Mater Interfaces ; 8(17): 10985-94, 2016 05 04.
Article in English | MEDLINE | ID: mdl-27064825

ABSTRACT

We report the first use of spark plasma sintering (SPS) as a single-step process to achieve superhydrophobic reduced graphene oxide (rGO). It was found that SPS was capable of converting smooth and electrically insulating graphene oxide (GO) sheets into highly electrically conductive rGO with minimum residual oxygen and hierarchical roughness which could be well retained after prolonged ultrasonication. At a temperature of 500 °C, which is lower than the conventional critical temperature for GO exfoliation, GO was successfully exfoliated, reduced, and hierarchically roughened. rGO fabricated by only 1 min of treatment at 1050 °C was superhydrophobic with a surface roughness (Ra) 10 times as large as that of GO as well as an extraordinarily high C:O ratio of 83.03 (atom %) and water contact angle of 153°. This demonstrates that SPS is a superior GO reduction technique, which enabled superhydrophobic rGO to be quickly and effectively achieved in one single step. Moreover, the superhydrophobic rGO fabricated by SPS showed an impressive bacterial antifouling and inactivation effect against Escherichia coli in both aqueous solution and the solid state. It is envisioned that the superhydrophobic rGO obtained in this study can be potentially used for a wide range of industrial and biomedical applications, such as the fabrication of self-cleaning and antibacterial surfaces.


Subject(s)
Graphite/chemistry , Anti-Bacterial Agents , Oxides , Temperature , Water
13.
Invest Ophthalmol Vis Sci ; 56(11): 6605-11, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26465888

ABSTRACT

PURPOSE: Synthetic keratoprostheses are required for visual rehabilitation in patients with end-stage corneal blindness. This study aimed to assess the biocompatibility of graphene material and its potential as a novel synthetic keratoprosthesis skirt material for corneal tissue engineering. METHODS: Human corneal stromal fibroblasts were cultured on material surfaces including pristine graphene film, graphene foam, pristine titanium (Ti) discs, and tissue culture plastic surface (TCPS). Cell attachment was assayed by immunostaining of paxillin and vinculin. Cell viability and proliferation were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Click iT 5-ethynyl-2'-deoxyuridine (EdU) assays. The growth of fibroblasts on three-dimensional graphene foam was examined by scanning electron microscopy, and cytokine release was analyzed by enzyme-linked immunosorbent assay. Graphene films were implanted into rabbit corneal stromal pockets and examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography, in vivo confocal microscopy, and histology. RESULTS: Pristine graphene demonstrated good biocompatibility with human stromal fibroblasts in terms of cell adhesion, viability, and proliferation. Cells on graphene films showed higher number than on TCPS control. Cells grown on graphene had 10% more proliferation than on Ti. The expression levels of IL-6 and IL-8 were reduced when cells were seeded on graphene foam as compared to Ti and graphene film. Implantation of graphene film into rabbit stroma (n = 6) did not show any signs of infection, neovascularization, or inflammation. CONCLUSIONS: Graphene displayed excellent short-term biocompatibility with corneal cells and tissue. This demonstrates that graphene can be developed as a tissue engineering material for use in cornea.


Subject(s)
Blindness/rehabilitation , Coated Materials, Biocompatible , Corneal Stroma/ultrastructure , Graphite , Prostheses and Implants , Tissue Engineering/methods , Animals , Humans , Male , Microscopy, Electron, Scanning , Prosthesis Design , Rabbits
14.
Biomaterials ; 67: 264-73, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26231917

ABSTRACT

The brain is an enormously complex organ structured into various regions of layered tissue. Researchers have attempted to study the brain by modeling the architecture using two dimensional (2D) in vitro cell culturing methods. While those platforms attempt to mimic the in vivo environment, they do not truly resemble the three dimensional (3D) microstructure of neuronal tissues. Development of an accurate in vitro model of the brain remains a significant obstacle to our understanding of the functioning of the brain at the tissue or organ level. To address these obstacles, we demonstrate a new method to bioprint 3D brain-like structures consisting of discrete layers of primary neural cells encapsulated in hydrogels. Brain-like structures were constructed using a bio-ink consisting of a novel peptide-modified biopolymer, gellan gum-RGD (RGD-GG), combined with primary cortical neurons. The ink was optimized for a modified reactive printing process and developed for use in traditional cell culturing facilities without the need for extensive bioprinting equipment. Furthermore the peptide modification of the gellan gum hydrogel was found to have a profound positive effect on primary cell proliferation and network formation. The neural cell viability combined with the support of neural network formation demonstrated the cell supportive nature of the matrix. The facile ability to form discrete cell-containing layers validates the application of this novel printing technique to form complex, layered and viable 3D cell structures. These brain-like structures offer the opportunity to reproduce more accurate 3D in vitro microstructures with applications ranging from cell behavior studies to improving our understanding of brain injuries and neurodegenerative diseases.


Subject(s)
Brain/physiology , Oligopeptides/pharmacology , Polysaccharides, Bacterial/pharmacology , Printing, Three-Dimensional , Animals , Brain/drug effects , Cattle , Cell Differentiation/drug effects , Cell Survival/drug effects , Cells, Cultured , Cerebral Cortex/cytology , Fluorescein-5-isothiocyanate/analogs & derivatives , Fluorescein-5-isothiocyanate/metabolism , Freeze Fracturing , Gels , Mice, Inbred BALB C , Neuroglia/cytology , Neuroglia/drug effects , Neurons/cytology , Neurons/drug effects , Porosity , Serum Albumin, Bovine/metabolism
15.
Adv Mater ; 27(46): 7563-82, 2015 Dec 09.
Article in English | MEDLINE | ID: mdl-25914294

ABSTRACT

The advent of implantable biomaterials has revolutionized medical treatment, allowing the development of the fields of tissue engineering and medical bionic devices (e.g., cochlea implants to restore hearing, vagus nerve stimulators to control Parkinson's disease, and cardiac pace makers). Similarly, future materials developments are likely to continue to drive development in treatment of disease and disability, or even enhancing human potential. The material requirements for implantable devices are stringent. In all cases they must be nontoxic and provide appropriate mechanical integrity for the application at hand. In the case of scaffolds for tissue regeneration, biodegradability in an appropriate time frame may be required, and for medical bionics electronic conductivity is essential. The emergence of graphene and graphene-family composites has resulted in materials and structures highly relevant to the expansion of the biomaterials inventory available for implantable medical devices. The rich chemistries available are able to ensure properties uncovered in the nanodomain are conveyed into the world of macroscopic devices. Here, the inherent properties of graphene, along with how graphene or structures containing it interface with living cells and the effect of electrical stimulation on nerves and cells, are reviewed.


Subject(s)
Biocompatible Materials/chemistry , Graphite/chemistry , Electric Stimulation , Humans , Oxides/chemistry , Stem Cells/cytology , Tissue Engineering , Tissue Scaffolds/chemistry
16.
Acta Biomater ; 14: 33-42, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25484333

ABSTRACT

A novel water-dispersible conducting polymer analogous to poly(3,4-dioxythiophene):polystyrene sulfonate (PEDOT:PSS) has been chemically synthesized in a single reaction in high yield. PEDOT:DS, a new member of the polythiophene family, is composed of a complex between PEDOT and the sulfonated polysaccharide polyanion dextran sulfate. Drop-cast films of aqueous suspensions of the material display a native conductivity of up to 7 ± 1 S cm(-1), increasing to 20 ± 2 S cm(-1) after treatment with ethylene glycol and thermal annealing. Mass ratios of the precursors NaDS and EDOT were varied from 5:1 to 2:1 and a decrease in the NaDS:EDOT ratio produces tougher, less hygroscopic films of higher conductivity. Ultraviolet-visible spectroelectrochemistry yields spectra typical of PEDOT complexes. Cyclic voltammetry reveals that PEDOT:DS is electrochemically active from -1.0 to 0.8 V vs. Ag/Ag(+) in acetonitrile, with similar characteristics to PEDOT:PSS. Water dispersions of PEDOT:DS are successfully processed by drop casting, spray coating, inkjet printing and extrusion printing. Furthermore, laser etching of dried films allows the creation of patterns with excellent definition. To assess the cytotoxicity of PEDOT:DS, L-929 cells were cultured with a polymer complex concentration range of 0.002 to 0.2 g l(-1) in cell culture medium. No significant difference is found between the proliferation rates of L-929 cells exposed to PEDOT:DS and those in plain medium after 96h. However, PEDOT:PSS shows around 25% less cell growth after 4 days, even at the lowest concentration. Taken together, these results suggest PEDOT:DS has exceptional potential as an electromaterial for the biointerface.


Subject(s)
Biopolymers/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Dextran Sulfate/pharmacology , Electric Conductivity , Organic Chemicals/pharmacology , Polymers/pharmacology , Animals , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Cell Line , Cell Proliferation/drug effects , Dextran Sulfate/chemical synthesis , Dextran Sulfate/chemistry , Electrochemical Techniques , Mice , Microscopy, Electron, Scanning , Oxidation-Reduction , Particle Size , Polymers/chemical synthesis , Polymers/chemistry , Spectrum Analysis , Temperature
17.
Anal Chem ; 85(7): 3521-5, 2013 Apr 02.
Article in English | MEDLINE | ID: mdl-23461486

ABSTRACT

We describe a solid state electrode structure based on a biologically derived proton-active redox center, riboflavin (RFN). The redox reaction of RFN is a pH-dependent process that requires no water. The electrode was fabricated using our previously described 'stuffing' method to entrap RFN into vapor phase polymerized poly(3,4-ethylenedioxythiophene). The electrode is shown to be capable of measuring the proton activity in the form of an effective pH over a range of different water contents including nonaqueous systems and ionic liquids (ILs). This demonstrates that the entrapment of the redox center facilitates direct electron communication with the polymer. This work provides a miniaturizable system to determine pH (effective) in nonaqueous systems as well as in ionic liquids. The ability to measure pH (effective) is an important step toward the ability to customize ILs with suitable pH (effective) for catalytic reactions and biotechnology applications such as protein preservation.

18.
Biomaterials ; 32(15): 3822-31, 2011 May.
Article in English | MEDLINE | ID: mdl-21353699

ABSTRACT

The dopant anion in polypyrrole plays a critical role in determining the physical and chemical properties of these conducting polymers. Here we demonstrate an additional effect on the ability to incorporate and release a neurotrophic protein - neurotrophin-3. The multi-faceted role of the dopant is critical in ensuring optimal performance of polypyrroles in their use as platforms for nerve growth. In this paper, the effect of changing the co-dopant used in electrochemical polypyrrole synthesis on the compatibility with primary auditory nerve tissue is considered and compared to some of the physical properties of the films. Significant differences in the controlled-release properties of the films were also observed. The ability of the polymers to enhance nerve growth and survival in vitro with neurotrophin-3 release was also studied, which is a function of both compatibility with the neural tissue and the ability of the polymer to release sufficient neurotrophic protein to affect cell growth. A small synthetic dopant, para-toluene sulphonate, was found to perform favourably in both aspects and ultimately proved to be the most suitable material for the application at hand, which is the delivery of neurotrophins for inner-ear therapies.


Subject(s)
Biocompatible Materials/chemistry , Cochlear Nerve/growth & development , Neurotrophin 3/administration & dosage , Polymers/chemistry , Pyrroles/chemistry , Animals , Biocompatible Materials/chemical synthesis , Cells, Cultured , Cochlear Nerve/drug effects , Electrochemical Techniques , Neurons/cytology , Neurons/drug effects , Neurotrophin 3/pharmacology , Polymers/chemical synthesis , Pyrroles/chemical synthesis , Rats , Rats, Wistar
19.
Nanoscale ; 2(4): 499-501, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20644750

ABSTRACT

An aligned CNT array membrane electrode has been used as a nanostructured supporting platform for polypyrrole (PPy) films, exhibiting significant improvement in the controlled release of neurotrophin. In terms of linearity of release, stimulated to unstimulated control of NT-3 release and increased mass and % release of incorporated NT-3, the nanostructured material performed more favourably than the flat PPy film.


Subject(s)
Drug Delivery Systems/instrumentation , Nanotubes, Carbon/chemistry , Neurotrophin 3/analysis , Polymers/chemistry , Pyrroles/chemistry , Electrodes , Nanotubes, Carbon/ultrastructure
20.
Macromol Rapid Commun ; 31(14): 1293-7, 2010 Jul 15.
Article in English | MEDLINE | ID: mdl-21567527

ABSTRACT

Glucose oxidase (GOx) is an important enzyme with great potential application for enzymatic sensing of glucose, in implantable biofuel cells for powering of medical devices in vivo and for large-scale biofuel cells for distributed energy generation. For these applications, immobilisation of GOx and direct transfer of electrons from the enzyme to an electrode material is required. This paper describes synthesis of conducting polymer (CP) structures in which GOx has been entrained such that direct electron transfer is possible between GOx and the CP. CP/enzyme composites prepared by other means show no evidence of such "wiring". These materials therefore show promise for mediator-less electronic connection of GOx into easily produced electrodes for biosensing or biofuel cell applications.

SELECTION OF CITATIONS
SEARCH DETAIL
...