Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface

Neural electrode devices hold great promise to help people with the restoration of lost functions, however, research is lacking in the biomaterial design of a stable, long-term device. Current devices lack long term functionality, most have been found unable to record neural activity within weeks after implantation due to the development of glial scar tissue (Polikov et al., 2006; Zhong and Bellamkonda, 2008). The long-term effect of chronically implanted electrodes is the formation of a glial scar made up of reactive astrocytes and the matrix proteins they generate (Polikov et al., 2005; Seil and Webster, 2008). Scarring is initiated when a device is inserted into brain tissue and is associated with an inflammatory response. Activated astrocytes are hypertrophic, hyperplastic, have an upregulation of intermediate filaments GFAP and vimentin expression, and filament formation (Buffo et al., 2010; Gervasi et al., 2008). Current approaches towards inhibiting the initiation of glial scarring range from altering the geometry, roughness, size, shape and materials of the device (Grill et al., 2009; Kotov et al., 2009; Kotzar et al., 2002; Szarowski et al., 2003). Literature has shown that surface topography modifications can alter cell alignment, adhesion, proliferation, migration, and gene expression (Agnew et al., 1983; Cogan et al., 2005; Cogan et al., 2006; Merrill et al., 2005). Thus, the goals of the presented work are to study the cellular response to biomaterials used in neural electrode fabrication and assess surface topography effects on minimizing astrogliosis. Initially, to examine astrocyte response to various materials used in neural electrode fabrication, astrocytes were cultured on platinum, silicon, PMMA, and SU-8 surfaces, with polystyrene as the control surface. Cell proliferation, viability, morphology and gene expression was measured for seven days in vitro. Results determined the cellular characteristics, reactions and growth rates of astrocytes grown on PMMA resembled closely to that of cells grown on the control surface, thus confirming the biocompatibility of PMMA. Additionally, the astrocyte GFAP gene expressions of cells grown on PMMA were lower than the control, signifying a lack of astrocyte reactivity. Based on the findings from the biomaterials study, it was decided to optimize PMMA by changing the surface characteristic of the material. Through the process of hot embossing, nanopatterns were placed on the surface in order to test the hypothesis that nanopattterning can improve the cellular response to the material. Results of this study agreed with current literature showing that topography effects protein and cell behavior. It was concluded that for the use in neural electrode fabrication and design, the 3600mm/gratings pattern feature sizes were optimal. The 3600 mm/gratings pattern depicted cell alignment along the nanopattern, less protein adsorption, less cell adhesion, proliferation and viability, inhibition of GFAP and MAP2k1 compared to all other substrates tested. Results from the initial biomaterials study also indicated platinum was negatively affected the cells and may not be a suitable material for neural electrodes. This lead to pursuing studies with iridium oxide and platinum alloy wires for the glial scar assay. Iridium oxide advantages of lower impedance and higher charge injection capacity would appear to make iridium oxide more favorable for neural electrode fabrication. However, results of this study demonstrate iridium oxide wires exhibited a more significant reactive response as compared to platinum alloy wires. Astrocytes cultured with platinum alloy wires had less GFAP gene expression, lower average GFAP intensity, and smaller glial scar thickness. Results from the nanopatterning PMMA study prompted a more thorough investigation of the nanopatterning effects using an organotypic brain slice model. PDMS was utilized as the substrate due to its optimal physical properties. Confocal and SEM imaging illustrated cells from the brain tissue slices were aligned along the nanopattern on the PDMS pins. Decreases in several inflammatory markers (GFAP, TNFα, IL-1β) determined from gene expression analysis, was shown with the nanopatterned PDMS pins. Results of this study confirm nanopatterning not only influences cell morphology, but alters molecular cascades within the cells as well. The results of these studies provide essential information for the neural electrode research community. There is a lack of information available in the scientific community on acceptable and effective materials for neural electrode fabrication. The results of the presented studies provide more information which could lead to classifying guidelines to create biocompatible neural electrode materials. This research project was partially supported by the Wayne State University President\u27s Translational Enhancement Award and by the Kales Scholarship for Biomedical Engineering students

A Human Body Mathematical Model Biometric Using Golden Ratio: A New Algorithm

This research provides more than 35 measurements rules derived from the perspectives of Vitruvian Man and Neufert and their basis of the golden proportion, to build a human body model on computers for the use of multimedia. The measurements are based on 25 proportional rules derived from 15 proportions given by Vitruvian Man and 29 golden proportions in Bauentwurfslehre by Ernst Neufert. Furthermore, the research will suggest two algorithms to calculate the 67 measurements with precision; assuming that the algorithms output will be used as guideline to human body modelers in simulation, gaming, plastic surgery, as well as the world of biometrics or wherever human body measurements and calculations is needed like prosthetic limbs, spatial design, and machine learning of human biometrics. Furthermore, building proportional models creates visual harmony in measurements and visual parity model. Hence, the chapter facilitates and explains for the human modeler the process of human modeling from within an algorithm. This research is an expanded work based on two published conference papers listed in the references section

Patientâ reported outcomes in a large North American cohort living with chronic hepatitis B virus: a crossâ sectional analysis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153747/1/apt15618_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153747/2/apt15618.pd

New Renewable and Biodegradable Particleboards from Jatropha Press Cakes

The influence of thermo-pressing conditions on the mechanical properties of particleboards obtained from Jatropha press cakes was evaluated in this study. Conditions such as molding temperature and press cake oil content were included. All particleboards were cohesive, with proteins and fibers acting respectively as binder and reinforcing fillers. Generally, it was the molding temperature that most affected particleboard mechanical properties. The most resistant boards were obtained using 200°C molding temperature. Glass transition of proteins then occurred during molding, resulting in effective wetting of the fibers. At this optimal molding temperature, the best compromise between flexural properties (7.2 MPa flexural strength at break and 2153 MPa elastic modulus), Charpy impact strength (0.85 kJ/m²) and Shore D surface hardness (71.6°), was a board obtained from press cake with low oil content (7.7%). Such a particleboard would be usable as interlayer sheets for pallets, for the manufacture of containers or furniture, or in the building trade

Fatigue in Patients with Chronic Hepatitis B Living in North America: Results from the Hepatitis B Research Network (HBRN)

Fatigue is a common symptom of liver disease but not well-characterized in patients with chronic hepatitis B virus (HBV)

Fatigue before, during and after antiviral therapy of chronic hepatitis C: Results from the Virahep-C study

Fatigue is the most frequent and often debilitating symptom of chronic hepatitis C. It is unclear whether successful therapy of hepatitis C leads to its clinical improvement. In the Virahep-C study, patients with hepatitis C virus (HCV) genotype 1 infection were treated with peginterferon alfa-2a and ribavirin for up to 48 weeks while undergoing assessment of viral kinetics and clinical symptoms

Status Epilepticus due to Intraperitoneal Injection of Vehicle Containing Propylene Glycol in Sprague Dawley Rats

Published reports of status epilepticus due to intraperitoneal injection containing propylene glycol in rats are sparse. In fact, there are no reports specifying a maximum safe dose of propylene glycol through intraperitoneal administration. We report here a case of unexpected seizures in Sprague Dawley rats after receiving an intraperitoneal injection containing propylene glycol. Nine-week-old, 225–250 gram male rats were reported to experience tremor progressing to seizures within minutes after given injections of resveratrol (30 mg/kg) dissolved in a 40 : 60 propylene glycol/corn oil vehicle solution by direct intraperitoneal (IP) slow bolus injection or via a preplaced intraperitoneal catheter. The World Health Organization suggests a maximum dose of 25 mg/kg/day of propylene glycol taken orally and no more than 25 mg/dL in blood serum, whereas the animals used in our study got a calculated maximum 0.52 g/kg (25 times lower dose). Blood tests from the seizing rat support a diagnosis of hemolysis and lactic acidosis which may have led to the seizures, all of which appeared to be a consequence of the propylene glycol administration. These findings are consistent with oral and intravenous administration of propylene glycol toxicity as previously reported in other species, including humans. To our knowledge, this report represents the first published case of status epilepticus due to an IP injection containing propylene glycol

Barriers to accessing care in patients with chronic hepatitis C: the impact of depression: Barriers to accessing healthcare for chronic hepatitis C

Patients with hepatitis C viral (HCV) may perceive barriers to accessing speciality care for HCV, and these barriers may be related to depressive symptoms