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

Electric Field Controlled, Pulsed Autoionization in Two Electron Wave Packets

In this paper, control of the evolution of a two electron wave packet through the application of a static electric field is demonstrated. Specifically, application of a small electric field is used to produce pulsed autoionization events, the timing of which can be controlled on a picosecond time scale. The technique is demonstrated by exciting calcium atoms using a short-pulsed laser to the 4p3/219d doubly excited state, which is energy degenerate with the 4p1/2nk stark states. Evolution of the resultant wave packet is monitored through the application of a second short laser pulse, which stimulates the atoms to emit a photon producing singly excited Rydberg states which are detected using field ionization

Direct Measurement of Oscillations between Degenerate Two-Electron Bound-State Configurations in a Rapidly Autoionizing System

In this paper we report a direct observation of the oscillation between bound-state configurations in a rapidly autoionizing system. Calcium atoms were excited to a pure 4p3/2nd two-electron configuration using a 500-fsec laser pulse. The initial 4p3/2nd doubly excited state is energy degenerate with the 4p1/2n\u27d states and several continuum channels. Because of the short-pulse excitation, the initial state of the atom is not an energy eigenstate, but a nonstationary wave packet. As a result, oscillations between the two bound configurations were produced. These oscillations were measured by scanning the timing of a second 500-fsec laser pulse tuned to drive the 4p1/2n\u27d ionic state back down to the 4sn\u27d singly excited configuration, which was subsequently detected using selective field ionization. A simple theoretical model was used to model the experimental results and produced good agreement with the data

Laser-Induced Stabilization of Autoionizing States

Stabilization of autoionizing states of barium by laser-induced, stimulated emission of light is demonstrated. Relative to purely flourescent stabilization, the data clearly show an enhancement of the stabilization process for laser pulses short compared to the flourescent lifetime of the autoionizing states. Shakeup spectra in which the principal quantum number of both electrons changes during the stimulated emission process are also clearly demonstrated

Shakeoff Measurement of the L = 3 States of Barium

Isolated core excitation was used to produce low-energy continuum electrons in the l = 3 angular momentum state of barium. Data were taken over a region of energy that coincided with the energy of the 6p3/2nf doubly excited states. Analysis of the data using multichannel quantum defect theory allowed the measurement of the widths of the 6p3/2nf states and the energy-dependent phase of the continuum electronic wave functions due to interaction with the doubly excited states. The phase of the continuum electrons is shown to vary continuously with energy, due to the anomalously broad widths of the double excited states

Short-pulse Laser-Induced Stabilization of Autoionizing States

Atoms in doubly excited states above the first ionization limit can decay via autoionization in which an electron is emitted leaving an ion, or by photoemission which leaves the atom in a singly excited state. In this paper, it is demonstrated that interaction between the atoms and a laser pulse that is short compared to the autoionization lifetime can lead to large enhancement of the photoemission process by stimulating the atoms to emit a photon. Since the resultant singly excited atoms do not autoionize, this process can be viewed as an enhancement of the stabilization of the doubly excited atoms against autoionization. A simple theoretical model is outlined that shows good agreement with the experimental results

Impact of adding palatal rugae to complete dentures on patient satisfaction and oral health-related quality of life: A randomized crossover clinical trial

STATEMENT OF PROBLEM: The addition of palatal rugae to complete dentures has been suggested to improve the satisfaction of patients with different oral functions. However, clinical studies to support these claims are lacking. PURPOSE: The purpose of this randomized, single-blind, 2-period crossover trial was to assess the satisfaction of edentulous patients and their oral health impact profile when provided with complete dentures with palatal rugae compared with a polished palate. MATERIAL AND METHODS: Edentulous patients aged 45 to 80 years, with no relevant medical conditions, seeking complete dentures at a university hospital between May and July 2019 were recruited. Each participant received new complete dentures. After a 1-week adaptation period, the participants were randomly allocated to 2 sequences through a computer-generated sequence. In the first sequence, palatal rugae were added to the complete dentures, and after 2 months, the palatal rugae were removed and the dentures used for another 2 months. In the second sequence, the opposite sequence was followed: polished palate first and palatal rugae second. After each period, a blinded dentist asked participants to rate their general satisfaction on a 100-mm visual analog scale (primary outcome) and to rate their satisfaction regarding eating, taste perception, speaking, phonetics, and ease of cleaning. Participants were also asked to fill the 20-item oral health impact profile for edentulous patients (OHIP-EDENT). The paired sample t test and the Wilcoxon test were used (α=.05). RESULTS: Fifty participants were randomized, of whom 6 dropped out. No significant differences were found between ratings for the 2 palatal contours in terms of general satisfaction 2.32 (95% confidence interval: -3.65 to 8.29, P=.438), eating 1.70 (95% confidence interval: -4.05 to 7.46, P=.554), taste perception 0.57 (95% confidence interval -5.04 to 6.17, P=.839), phonetics 1.48 (95% confidence interval -4.46 to 7.41, P=.618), or speaking 3.68 (95% confidence interval: -1.92 to 9.28, P=.192). However, satisfaction with ease of cleaning dentures with palatal rugae was significantly less 12.16 (95% confidence interval: 6.81 to 17.50, P.05), except for the frequency of mealtime interruption (P=.041), which was reported to increase when rugae had been provided. CONCLUSIONS: Complete dentures with palatal rugae were not perceived to improve patient satisfaction or oral health-related quality of life. However, they were perceived to be more difficult to clean and to increase frequency of interruptions during eating

Experimental observation of autosoliton propagation in a dispersion-managed system guided by nonlinear optical loop mirrors

Observation of autosoliton propagation in a dispersion-managed optical transmission system controlled by in-line nonlinear fiber loop switches is reported for what is believed to be the first time. The system is based on a strong dispersion map with large amplifier spacing. Operation at transmission rates of 10 and 40 Gbits/s is demonstrated. ©2004 Optical Society of America

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