Effect of oral exposure on chemical, physical, mechanical, and morphologic properties of clear orthodontic aligners.

INTRODUCTION: The dental industry is heavily committed to developing more esthetic solutions for orthodontic treatments. Invisalign is a system of transparent orthodontic aligners introduced as an alternative to conventional orthodontic fittings with brackets and metal wires. This study aimed to assess the chemical, physical, mechanical and morphologic changes in these polymeric aligners after exposure to the oral environment. METHODS: Twenty-four Invisalign orthodontic aligners were equally divided into 2 groups: an in vivo aged group in which patients used aligners for 14 days and the reference group, unexposed to the oral environment. Different experimental techniques were used to study the chemical structure, the color changes and translucency, the density and subsequent volume of the aligners, mechanical properties, surface roughness, morphology and elemental composition. The data were subjected to several statistical analyses. RESULTS: Clear orthodontic aligners exhibit chemical stability but undergo a statistically significant optical change in color and translucency. There was a gradual increase in the water absorption rate and the dimensional variation of the polymer, indicating a strong correlation among these factors. The mechanical properties of the polymer showed a statistically significant decrease in its elastic modulus and hardness. There was a slight tendency toward increased surface roughness of the material, but no statistical differences were found between reference and aged groups. The surface morphology of the used aligners demonstrates microcracks, distortions and biofilm formation. CONCLUSION: Intraoral aging adversely affected the physical, mechanical, and morphologic properties of the Invisalign appliance.

Evaluation of Packaging Materials in Freeze-Drying: Use of Polymer Caps and Nested Vials and Their Impact on Process and Product Attributes.

Current trends in the pharmaceutical industry led to a demand for more flexible manufacturing processes with smaller batch sizes. Prepackaged nested vials that can be processed as a unit were introduced into the market to fulfill this need. However, vial nests provide a different thermal environment for the vials compared to a hexagonal packaging array and could therefore influence product temperature profiles, primary drying times, and product quality attributes. Polymer caps with the possibility of vial closure inside the freeze-drying chamber were developed to remove the risks and need of a crimping process. A general concern with the use of such caps is the possibility of an increase in resistance to water vapor flow out of the vial. This case study investigated the effect of the LyoSeal® and PLASCAP® polymer caps and EZ-fill® nests on the freeze-drying process. Amorphous and partially crystalline model formulations were freeze-dried. Process data and product quality attributes were compared for regularly stoppered vials and vials with polymer caps as well as vials in a hexagonal packaging array and nested vials. The results indicated no increased resistance or impeded water vapor flow by the polymer caps. Differences in the macro- and microscopic appearances of products and a trend towards lower product temperatures were observed for the investigated nest type compared to a regular hexagonal packaging array. Consequently, the polymer caps could be used as an alternative to regular stoppers without affecting freeze-drying process data or product quality attributes, while the different thermal environment of nested vials should be considered.

Electrospinning/electrospraying coatings for metal microneedles: A design of experiments (DOE) and quality by design (QbD) approach.

The research presented here shows QbD implementation for the optimisation of the key process parameters in electrohydrodynamic atomisation (EHDA). Here, the electrosprayed nanoparticles and electrospun fibers consisting of a polymeric matrix and dye. Eight formulations were assessed consisting of 5% w/v of polycaprolactone (PCL) in dichloromethane (DCM) and 5% w/v polyvinylpyrrolidone (PVP) in ethanol. A full factorial DOE was used to assess the various parameters (applied voltage, deposition distance, flow rate). Further particle and fiber analysis using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared Spectroscopy (FTIR), particle/fiber size distribution. In addition to this in vitro release studied were carried out using fluorescein and Rhodamine B as model dyes and in vitro permeation studies were applied. The results show a significant difference in the morphology of resultant structures as well as a more rapid release profile for the PVP particles and fibers in comparison to the sustained release profiles found with PCL. In vitro drug release studies showed 100% drug release after 7 days for PCL particles and showed 100% drug release within 120 min for PVP particles. The release kinetics and the permeation study showed that the MN successfully pierced the membrane and the electrospun MN coating released a large amount of the loaded drug within 6 h. This study has demonstrated the capability of these robust MNs to encapsulate a diverse range drugs within a polymeric matrix giving rise to the potential of developed personalised medical devices.

PEEK versus titanium cages in lateral lumbar interbody fusion: a comparative analysis of subsidence.

OBJECTIVE: The authors have provided a review of radiographic subsidence after lateral lumbar interbody fusion (LLIF) as a comparative analysis between titanium and polyetheretherketone (PEEK) cages. Many authors describe a reluctance to use titanium cages in spinal fusion secondary to subsidence concerns due to the increased modulus of elasticity of metal cages. The authors intend for this report to provide observational data regarding the juxtaposition of these two materials in the LLIF domain. METHODS: A retrospective review of a prospectively maintained database identified 113 consecutive patients undergoing lateral fusion for degenerative indications from January to December 2017. The surgeons performing the cage implantations were two orthopedic spine surgeons and two neurosurgeons. Plain standing radiographs were obtained at 1-2 weeks, 8-12 weeks, and 12 months postoperatively. Using a validated grading system, interbody subsidence into the endplates was graded at these time points on a scale of 0 to III. The primary outcome measure was subsidence between the two groups. Secondary outcomes were analyzed as well. RESULTS: Of the 113 patients in the sample, groups receiving PEEK and titanium implants were closely matched at 57 and 56 patients, respectively. Cumulatively, 156 cages were inserted and recombinant human bone morphogenetic protein-2 (rhBMP-2) was used in 38.1%. The average patient age was 60.4 years and average follow-up was 75.1 weeks. Subsidence in the titanium group in this study was less common than in the PEEK cage group. At early follow-up, groups had similar subsidence outcomes. Statistical significance was reached at the 8- to 12-week and 52-week follow-ups, demonstrating more subsidence in the PEEK cage group than the titanium cage group. rhBMP-2 usage was also highly correlated with higher subsidence rates at all 3 follow-up time points. Age was correlated with higher subsidence rates in univariate and multivariate analysis. CONCLUSIONS: Titanium cages were associated with lower subsidence rates than PEEK cages in this investigation. Usage of rhBMP-2 was also robustly associated with higher endplate subsidence. Each additional year of age correlated with an increased subsidence risk. Subsidence in LLIF is likely a response to a myriad of factors that include but are certainly not limited to cage material. Hence, the avoidance of titanium interbody implants secondary solely to concerns over a modulus of elasticity likely overlooks other variables of equal or greater importance.

A three-dimensional printed photopolymer resin implant for orbital rehabilitation for evisceration / Implante de resina fotocurável para evisceração produzido por impressora tridimensional

ABSTRACT Purpose: To evaluate the biocompatibility of three-dimensional (3D) printed orbital spheres for evisceration. Materials: A total of 10 consecutive patients (eight females and two males; mean age, 46.8 ± 14.2 years) underwent evisceration of blind painful eyes. 3D spherical implants produced by a rapid prototype machine were used to restore orbital volume. The implants were produced from a commercially available photocurable resin (Fullcure®). Systemic toxicity was evaluated by comparing serum biochemical measurements (creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, albumin, creatinine, urea, alkaline phosphatase, and C-reactive protein) before and at 12 months after surgery. Local toxicity was assessed by the evaluation of signs of socket inflammation at the first postoperative month. Changes in implant size were determined by computed tomography scans at 2 and 12 months after surgery. Results: The postoperative evaluations were uneventful. The biochemical evaluation showed no significant changes after surgery. None of the patients presented signs of orbital implant inflammation, infection, exposure, or extrusion. Computed tomography scan evaluations revealed no changes in implant size. Conclusion: To the best of our knowledge, this is the first phase-1 clinical study to certify the biocompatibility of the Fullcure resin for orbital implants in humans. The 3D printing technology permits fast and accurate production of implants for this purpose.

RESUMO Objetivos: Avaliar a biocompatibilidade das esferas produzidas por impressora tridimensional em evisceração. Pacientes e métodos: Evisceração por olho cego doloroso foi realizada em 10 pacientes consecutivos (8 mulheres, idade média: 46.8 ± 14.2 anos). Os implantes esféricos foram produzidos pelo sistema de prototipagem rápida utilizando dados tridimensionais computadorizados. O material utilizado para produção dos implantes foi a resina fotocurável Fullcure®. A avaliação da toxicidade sistêmica do material foi realizada por meio da dosagem de marcadores bioquímicos (creatina fosfoquinase, aspartato aminotransferase, alanina aminotransferase, albumina, creatinina, ureia, fosfatase alcalina, e proteína C-reactiva) antes da cirurgia e aos 12 meses de pós-operatorio. A avaliação da toxicidade local foi realizada por meio do registro qualitativo dos sinais inflamatórios no lado operado durante o primeiro mês de pós-operatório. O tamanho dos implantes foi medido em tomografias computadorizadas (CT) aos 2 e 12 meses de pós-operatório. Resultados: A avaliação bioquímica mostrou que os marcadores estudados não sofreram alterações significativas após a cirurgia. Nenhum paciente apresentou sinais de inflamação atípica, infecção, exposição ou extrusão. A avaliação tomográfica não demonstrou mudanças nos tamanhos dos implantes. Conclusão: O presente trabalho é o primeiro estudo clínico realizado para atestar a biocompatibilidade dos implantes orbitais de resina fotocurável Fullcure. A produção dos implantes pela técnica de impressão tridimensional, utilizando essa resina, permite a disponibilização rápida e acurada do produto final

Chronic Implantation of Multiple Flexible Polymer Electrode Arrays.

Simultaneous recordings from large populations of individual neurons across distributed brain regions over months to years will enable new avenues of scientific and clinical development. The use of flexible polymer electrode arrays can support long-lasting recording, but the same mechanical properties that allow for longevity of recording make multiple insertions and integration into a chronic implant a challenge. Here is a methodology by which multiple polymer electrode arrays can be targeted to a relatively spatially unconstrained set of brain areas. The method utilizes thin-film polymer devices, selected for their biocompatibility and capability to achieve long-term and stable electrophysiologic recording interfaces. The resultant implant allows accurate and flexible targeting of anatomically distant regions, physical stability for months, and robustness to electrical noise. The methodology supports up to sixteen serially inserted devices across eight different anatomic targets. As previously demonstrated, the methodology is capable of recording from 1024 channels. Of these, the 512 channels in this demonstration used for single neuron recording yielded 375 single units distributed across six recording sites. Importantly, this method also can record single units for at least 160 days. This implantation strategy, including temporarily bracing each device with a retractable silicon insertion shuttle, involves tethering of devices at their target depths to a skull-adhered plastic base piece that is custom-designed for each set of recording targets, and stabilization/protection of the devices within a silicone-filled, custom-designed plastic case. Also covered is the preparation of devices for implantation, and design principles that should guide adaptation to different combinations of brain areas or array designs.

A three-dimensional printed photopolymer resin implant for orbital rehabilitation for evisceration.

PURPOSE: To evaluate the biocompatibility of three-dimensional (3D) printed orbital spheres for evisceration. MATERIALS: A total of 10 consecutive patients (eight females and two males; mean age, 46.8 ± 14.2 years) underwent evisceration of blind painful eyes. 3D spherical implants produced by a rapid prototype machine were used to restore orbital volume. The implants were produced from a commercially available photocurable resin (Fullcure®). Systemic toxicity was evaluated by comparing serum biochemical measurements (creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, albumin, creatinine, urea, alkaline phosphatase, and C-reactive protein) before and at 12 months after surgery. Local toxicity was assessed by the evaluation of signs of socket inflammation at the first postoperative month. Changes in implant size were determined by computed tomography scans at 2 and 12 months after surgery. RESULTS: The postoperative evaluations were uneventful. The biochemical evaluation showed no significant changes after surgery. None of the patients presented signs of orbital implant inflammation, infection, exposure, or extrusion. Computed tomography scan evaluations revealed no changes in implant size. CONCLUSION: To the best of our knowledge, this is the first phase-1 clinical study to certify the biocompatibility of the Fullcure resin for orbital implants in humans. The 3D printing technology permits fast and accurate production of implants for this purpose.

Reliability of parylene-based multi-electrode arrays chronically implanted in adult rat brains, and evidence of electrical stimulation on contact impedance.

OBJECTIVE: The goal of this study was to evaluate the long-term behavior of the surface electrode through electrochemical characterization and follow-up of implanted parylene/platinum microelectrodes. APPROACH: To this aim, we designed and manufactured specific planar electrodes for cortical implantation for a rat model. This work was included in the INTENSE® project, one of the goals of which was to prove the feasibility of selective neural recording or stimulation with cuff electrodes around the vagus nerve. MAIN RESULTS: After a 12-week implantation in a rat model, we can report that these microelectrodes have withstood in vivo use. Regarding the biocompatibility of the electrodes (materials and manufacturing process), no adverse effect was reported. Indeed, after the three-month implantation, we characterized limited tissue reaction beneath the electrodes and showed an increase and a stabilization of their impedance. Interestingly, the follow-up of the electrochemical impedance combined with electrical stimulation highlighted a drop in the impedance up to 60% at 1 kHz after ten minutes of electrical stimulation at 110 Hz. SIGNIFICANCE: This study gives evidence of the biocompatibility of the parylene platinum contact array designed for the project and confirms the effect of stimulation on the contact impedance.

Comparison of the biodegradable polymer everolimus-eluting stent with contemporary drug-eluting stents: A systematic review and meta-analysis.

AIMS: Despite similar efficacy and safety profile in pilot studies, bioresorbable polymer drug-eluting stents (BP-DES) could have potential benefit over latest generation durable polymer (DP)-DES by facilitating vessel healing, therefore reducing inflammation and neoatherosclerosis leading to enhanced clinical safety. Therefore, we sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of everolimus-eluting BP-DES (BP-EES) to second-generation DP-DES. METHODS AND RESULTS: We conducted a systematic review and meta-analysis to examine the safety and efficacy of BP-EES in patients treated for coronary artery disease. We searched PubMed, Scopus, and the Cochrane Library through February 2018 for RCTs that included outcome data on BP-EES. We identified four eligible studies, which included a total of 4631 patients. Three studies reported a follow-up of one year and one study of five years. The BP-EES group, included 2315 patients and the DP-DES group included 2316 patients (1143 treated with DP-EES and 1173 treated with zotarolimus eluting DP-DES). Patient's characteristics were comparable between the two groups except for higher prevalence of prior MI in the DP-DES group (25.7 vs 22.5%, respectively, p = 0.001). Procedural characteristics were comparable among groups except for slightly longer lesions in the BP-EES group compared to the DP-DES group (mean 15.1 vs 14.9 mm, p = 0.04). No significant differences were observed for cardiac mortality (p = 0.72), occurrence of MI (p = 0.64), any TLR (p = 0.93), ST (p = 0.85) or major adverse cardiac events (p = 0.43). CONCLUSION: Overall, based on the available data BP-EES had similar one-year outcomes to contemporary DP-DES. Whether these devices could enhance clinical safety remains to be evaluated at longer follow-up.

High-Density, Long-Lasting, and Multi-region Electrophysiological Recordings Using Polymer Electrode Arrays.

The brain is a massive neuronal network, organized into anatomically distributed sub-circuits, with functionally relevant activity occurring at timescales ranging from milliseconds to years. Current methods to monitor neural activity, however, lack the necessary conjunction of anatomical spatial coverage, temporal resolution, and long-term stability to measure this distributed activity. Here we introduce a large-scale, multi-site, extracellular recording platform that integrates polymer electrodes with a modular stacking headstage design supporting up to 1,024 recording channels in freely behaving rats. This system can support months-long recordings from hundreds of well-isolated units across multiple brain regions. Moreover, these recordings are stable enough to track large numbers of single units for over a week. This platform enables large-scale electrophysiological interrogation of the fast dynamics and long-timescale evolution of anatomically distributed circuits, and thereby provides a new tool for understanding brain activity.

Conversion of calibration curves for accurate estimation of molecular weight averages and distributions of polyether polyols by conventional size exclusion chromatography.

Accurate measurement of molecular weight averages (M¯n,M¯w,M¯z) and molecular weight distributions (MWD) of polyether polyols by conventional SEC (size exclusion chromatography) is not as straightforward as it would appear. Conventional calibration with polystyrene (PS) standards can only provide PS apparent molecular weights which do not provide accurate estimates of polyol molecular weights. Using polyethylene oxide/polyethylene glycol (PEO/PEG) for molecular weight calibration could improve the accuracy, but the retention behavior of PEO/PEG is not stable in THF-based (tetrahydrofuran) SEC systems. In this work, two approaches for calibration curve conversion with narrow PS and polyol molecular weight standards were developed. Equations to convert PS-apparent molecular weight to polyol-apparent molecular weight were developed using both a rigorous mathematical analysis and graphical plot regression method. The conversion equations obtained by the two approaches were in good agreement. Factors influencing the conversion equation were investigated. It was concluded that the separation conditions such as column batch and operating temperature did not have significant impact on the conversion coefficients and a universal conversion equation could be obtained. With this conversion equation, more accurate estimates of molecular weight averages and MWDs for polyether polyols can be achieved from conventional PS-THF SEC calibration. Moreover, no additional experimentation is required to convert historical PS equivalent data to reasonably accurate molecular weight results.

Baxter elastomeric pumps: Weighing as an alternative to visual inspection.

Purpose Elastomeric pumps are used to administer 46-hour infusions of 5-fluorouracil (5FU). Baxter suggests patients visually monitor their pumps to ensure that infusions are proceeding correctly. This can be confusing and lead to concerns about under- or over-dosing. Baxter has not considered weighing pumps as a validated method for monitoring. This study aims to validate weighing as a more accurate method for patients and healthcare professionals, and describe real life Baxter Infusor™ variability. Methods Patients who had been started on a 46-hour 5FU infusion returned to the clinic approximately 24 h after starting treatment. The pump was weighed on a StarFrit kitchen scale, and date, time, and weights recorded. Patients were asked if they had a preference for weighing or visually inspecting their pump. Results Pumps ( n = 103) were weighed between 17.25 and 27.5 h after connection. The average weight of a pump was 189 g. Of 103 pumps weighed, 99 weighed less than expected, corresponding to average flow rates of 5.69 mL/h over the elapsed time. The expected flow rate is 5 mL/h with 10% variability. Average flow rates within the 17.25- to 27.5-hour window were 4.561 mL/h, which is 8.78% slower than expected, but within the 10% known variability. Forty-seven percent of patients didn't have a preference for either method, but for those who did have a preference, more than twice as many preferred weighing. Conclusion With proper education, weighing Baxter Infusors at home with kitchen scales can be an accepted and objective alternative to the current recommendation of visual inspection.

A review on mechanical considerations for chronically-implanted neural probes.

This review intends to present a comprehensive analysis of the mechanical considerations for chronically-implanted neural probes. Failure of neural electrical recordings or stimulation over time has shown to arise from foreign body reaction and device material stability. It seems that devices that match most closely with the mechanical properties of the brain would be more likely to reduce the mechanical stress at the probe/tissue interface, thus improving body acceptance. The use of low Young's modulus polymers instead of hard substrates is one way to enhance this mechanical mimetism, though compliance can be achieved through a variety of means. The reduction of probe width and thickness in comparison to a designated length, the use of soft hydrogel coatings and the release in device tethering to the skull, can also improve device compliance. Paradoxically, the more compliant the device, the more likely it will fail during the insertion process in the brain. Strategies have multiplied this past decade to offer partial or temporary stiffness to the device to overcome this buckling effect. A detailed description of the probe insertion mechanisms is provided to analyze potential sources of implantation failure and the need for a mechanically-enhancing structure. This leads us to present an overview of the strategies that have been put in place over the last ten years to overcome buckling issues. Particularly, great emphasis is put on bioresorbable polymers and their assessment for neural applications. Finally, a discussion is provided on some of the key features for the design of mechanically-reliable, polymer-based next generation of chronic neuroprosthetic devices.

Sterilization of implantable polymer-based medical devices: A review.

This review article is focused on the sterilization techniques used for polymer-based implantable medical devices as well as the regulatory aspects governing sterile medical devices. Polymeric materials are increasingly used in implantable devices due to their biodegradable and biocompatible nature. Patients and medical staff often prefer long-term implantable devices and these can be achieved using high molecular weight polymers. Sterilization of polymer-based implantable devices is critical. Since all implantable devices must be sterile, the effect of the sterilization method on the different device components (such as, the polymer, the drug, the electronics, etc.) has to be considered. A comprehensive summary of the established sterilization methods is provided along with the possible effects on polymers. In addition, novel sterilization methods are also discussed.

Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders.

The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all critical sources of variability which could affect this granulation technique. The purpose of this study was to provide an in-depth analysis of the continuous TSMG process in order to expose the critical process parameters (CPP) and elucidate the impact of process and formulation parameters on the critical quality attributes (CQA) of granules and tablets during continuous TSMG. A first part of the study dealt with the screening of various amorphous polymers as binder for producing high-dosed melt granules of two model drug (i.e. acetaminophen and hydrochlorothiazide). The second part of this study described a quality-by-design (QbD) approach for melt granulation of hydrochlorothiazide in order to thoroughly evaluate TSMG, milling and tableting stage of the continuous TSMG line. Using amorphous polymeric binders resulted in melt granules with high milling efficiency due to their brittle behaviour without producing excessive amounts of fines, providing high granule yields with low friability. Therefore, it makes them extremely suitable for further downstream processing. One of the most important CPP during TSMG with polymeric binders was the granulation-torque, which - in case of polymers with high Tg - increased during longer granulation runs to critical levels endangering the continuous process flow. However, by optimizing both screw speed and throughput or changing to polymeric binders with lower Tg it was possible to significantly reduce this risk. This research paper highlighted that TSMG must be considered as a viable option during formulation development of solid oral dosage forms based on the robustness of the CQA of both melt granules and tablets.

Comparison of a Lyophilized Drug Product to Other Solid and Liquid Media for the Extraction of Elastomeric Oligomers from a Butyl Rubber Stopper.

Lyophilization is commonly used to extend the shelf life of pharmaceutical products that are otherwise unstable when stored as a liquid formulation. However, the ability of a lyophilized drug, or other solid medium, to leach or extract substances from a pharmaceutical packaging material is not well characterized. To provide insight into this area of uncertainty, the extraction properties of a lyophilized drug product, the lyophilized drug product reconstituted in water, and several other solid and liquid media of varying polarity were determined using a glass vial with a butyl rubber stopper as a representative pharmaceutical packaging system. The results obtained in this study show that the extracting power of a medium, whether solid or liquid, was primarily a function of polarity. Thus, the amount of each extractable observed for the lyophilized and reconstituted drug product were in trend with the other solid and liquid media, respectively. Nevertheless, it was notable that the lyophilized drug product was able to leach substances from the stopper in quantifiable amounts, whereas the reconstituted drug product contained no detectable leachables. Using a mathematical relationship, it was determined that the extraction power of the lyophilized drug product was equivalent to a 50/50 isopropanol/water solution.LAY ABSTRACT: Freeze drying is commonly used to extend the shelf life of pharmaceutical products that are otherwise unstable when stored as a liquid formulation. However, the propensity for substances to migrate from a pharmaceutical packaging material and into a solid drug formulation is not well characterized. To provide insight into this area of uncertainty, the migration of substances from a glass vial with a butyl rubber stopper and into a lyophilized drug product, the drug product reconstituted with water, as well as several solid and liquid media of varying polarity were assessed. The results obtained in this study show that the extracting power of a medium, whether solid or liquid, was primarily a function of polarity and thus could be related to one another. Furthermore, the results for the freeze-dried and reconstituted drug products were in trend with the other solid and liquid media tested, respectively, and showed that the freeze-dried drug was able to leach substances from the stopper in measureable amounts, whereas the reconstituted drug product contained no substances that had originated from the stopper.

Analysis of Al2O3-parylene C bilayer coatings and impact of microelectrode topography on long term stability of implantable neural arrays.

OBJECTIVE: Performance of many dielectric coatings for neural electrodes degrades over time, contributing to loss of neural signals and evoked percepts. Studies using planar test substrates have found that a novel bilayer coating of atomic-layer deposited (ALD) Al2O3 and parylene C is a promising candidate for neural electrode applications, exhibiting superior stability to parylene C alone. However, initial results from bilayer encapsulation testing on non-planar devices have been less positive. Our aim was to evaluate ALD Al2O3-parylene C coatings using novel test paradigms, to rigorously evaluate dielectric coatings for neural electrode applications by incorporating neural electrode topography into test structure design. APPROACH: Five test devices incorporated three distinct topographical features common to neural electrodes, derived from the utah electrode array (UEA). Devices with bilayer (52 nm Al2O3 + 6 µm parylene C) were evaluated against parylene C controls (N ⩾ 6 per device type). Devices were aged in phosphate buffered saline at 67 °C for up to 311 d, and monitored through: (1) leakage current to evaluate encapsulation lifetimes (>1 nA during 5VDC bias indicated failure), and (2) wideband (1-105 Hz) impedance. MAIN RESULTS: Mean-times-to-failure (MTTFs) ranged from 12 to 506 d for bilayer-coated devices, versus 10 to >2310 d for controls. Statistical testing (log-rank test, α = 0.05) of failure rates gave mixed results but favored the control condition. After failure, impedance loss for bilayer devices continued for months and manifested across the entire spectrum, whereas the effect was self-limiting after several days, and restricted to frequencies <100 Hz for controls. These results correlated well with observations of UEAs encapsulated with bilayer and control films. SIGNIFICANCE: We observed encapsulation failure modes and behaviors comparable to neural electrode performance which were undetected in studies with planar test devices. We found the impact of parylene C defects to be exacerbated by ALD Al2O3, and conclude that inferior bilayer performance arises from degradation of ALD Al2O3 when directly exposed to saline. This is an important consideration, given that neural electrodes with bilayer coatings are expected to have ALD Al2O3 exposed at dielectric boundaries that delineate electrode sites. Process improvements and use of different inorganic coatings to decrease dissolution in physiological fluids may improve performance. Testing frameworks which take neural electrode complexities into account will be well suited to reliably evaluate such encapsulation schemes.

A New Polysulfone Membrane Dialyzer, NV, with Low-Fouling and Antithrombotic Properties.

BACKGROUND: The biggest problem in routine hemodialysis therapy is possibly the blood pressure fall experienced by patients during dialysis. In contrast, in medium- and long-term hemodialysis therapy, the main problem might be deterioration of arteriosclerosis because of medial calcification associated with dialysis vintage. Both problems are caused by an autonomic imbalance or structural change in the blood vessels. Inflammation due to extracorporeal blood circulation is another possible cause. This inflammation is considered to cause platelets activated by contact and adherence with the membrane surface to aggregate with white blood cells and attack the endothelium of the blood vessels. Therefore, we tried to develop a new membrane with no adsorption and no platelet activation. SUMMARY: Polysulfone (PS) membranes with polyvinylpyrrolidone (PVP) as a hydrophilic agent are widely used in dialysis, but blood components adhere to the membrane surface. We developed a new dialyzer, NV, by localizing a new hydrophilic polymer onto the inner surface of a hollow-fiber membrane composed of PS and PVP. The number of platelets that adhered to the NV membrane surface drastically decreased to 0.9% of that with the conventional PS dialysis membrane. We also confirmed the mechanism by which NV realizes clinical improvements in blood pressure drops and inflammation during dialysis, and verified its clinical appeal. Key Messages: The new membrane NV, which inhibits platelet adhesion and is compatible with blood vessels, is clinically beneficial.

Removal of free light chains in hemodialysis patients without multiple myeloma: a crossover comparison of three different dialyzers.

BACKGROUND: Immunoglobulin light chains are classified as middle molecule uremic toxins able to interact with B lymphocyte membranes leading to the activation of transmembrane signaling. The ensuing impairment of neutrophil function can contribute to the chronic inflammation state of uremic patients, and the increased risk of bacterial infections or vascular calcifications. The aim of this crossover observational study was to assess the difference in free light chain removal by three different hemodialysis filters in patients not affected by multiple myeloma. METHODS: Free light chain removal was compared in the polymethylmethacrylate (PMMA) membrane Filtryzer BK-F, the polyphenylene HFR17 filter and the conventional polysulfone filter F7HPS. Twenty chronic hemodialysis patients were enrolled: mean age was 67.7 ± 17.0 years, M/F = 14/6, dialysis vintage (months) 25.5 ± 32.0. The patients were randomized into two groups of treatment lasting 6 weeks each. The dialysis sessions checked were the midweek sessions and the blood was drawn at times 0, 120' and 240'. Kappa (k) and lambda (λ) light chain levels, ß2microglobulin (ß2M), C reactive protein (CRP) and albumin were checked. RESULTS: K light chain levels were 345.0 ± 100.0 mg/L, λ light chains were 121.4 ± 27.0 mg/L. The values of k light chains at times 120' and 240' were significantly lower with PMMA and HFR17 than those obtained with F7. The reduction ratio per session (RRs) for k light chains was 44.1 ± 4.3% with HFR17, 55.3 ± 3.4% with PMMA, 25.7 ± 8.3% with F7 (p = 0.018). The RRs for λ light chains was 30.3 ± 2.9% with HFR17, 37.8 ± 17.3% with PMMA, 14.0 ± 3.9% with F7 (p = 0.032). As to ß2M, RRs was 42.4 ± 3.2% with HFR17 vs. 33.9 ± 2.8% with PMMA vs. 6.3 ± 1.9% with F7 (p = 0.022). The three filters tested showed no differences in CRP or albumin levels. CONCLUSION: In terms of light chain and ß2M removal, the PMMA and on-line HFR filters are similar and both are significantly more effective than the F7 filter in chronic dialysis patients. TRIAL REGISTRATION: The present trial was registered retrospectively ( NCT02950389 , 31/10/2016).