Stability of flexible thin-film metallization stimulation electrodes: analysis of explants after first-in-human study and improvement of in vivo performance

ABSTRACTMicro-fabricated neural interfaces based on polyimide (PI) are achieving increasing importance in translational research. The ability to produce well-defined micro-structures with properties that include chemical inertness, mechanical flexibility and low water uptake are key advantages for these devices. This paper reports the development of the transverse intrafascicular multichannel electrode (TIME) used to deliver intraneural sensory feedback to an upper-limb amputee in combination with a sensorized hand prosthesis. A first-in-human study limited to 30 days was performed. About 90 % of the stimulation contact sites of the TIMEs maintained electrical functionality and stability during the full implant period. However, optical analysis post-explantation revealed that 62.5 % of the stimulation contacts showed signs of mechanical damage at the metallization-PI interface. Such damage likely occurred due to handling during explantation and subsequent analysis, since a significant change in impedance was not observed in vivo. Nevertheless, whereas device integrity is mandatory for long-term functionality in chronic implantation, measures to increase the bonding strength of the metallization-PI interface deserve further investigation. We report here that silicon carbide (SiC) is an effective adhesion-promoting layer resisting heavy electrical stimulation conditions in vivo. Optical analysis of the new electrodes revealed that the metallization remained unaltered after delivering over 14 million pulses in vivo without signs of delamination at the metallization-PI interface. Reliable adhesion of thin-film metallization to substrate has been proven using SiC, improving the potential transfer of micro-fabricated neural electrodes for chronic clinical applications.

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Force Generation on the Hallux Is More Affected by the Ankle Joint Angle than the Lesser Toes: An In Vivo Human Study

Biology ◽

10.3390/biology10010048 ◽

2021 ◽

Vol 10 (1) ◽

pp. 48

Author(s):

Junya Saeki ◽

Soichiro Iwanuma ◽

Suguru Torii

Keyword(s):

Repeated Measures ◽

Joint Angle ◽

Plantar Flexion ◽

Human Study ◽

Force Generation ◽

Functional Difference ◽

Multiple Comparison Test ◽

The Difference ◽

Metatarsophalangeal Joints

The structure of the first toe is independent of that of the other toes, while the functional difference remains unclear. The purpose of this study was to investigate the difference in the force generation characteristics between the plantar-flexion of the first and second–fifth metatarsophalangeal joints (MTPJs) by comparing the maximal voluntary plantar-flexion torques (MVC torque) at different MTPJs and ankle positions. The MVC torques of the first and second–fifth MTPJs were measured at 0°, 15°, 30°, and 45° dorsiflexed positions of the MTPJs, and at 20° plantar-flexed, neutral, and 20° dorsiflexed positions of the ankle. Two-way repeated measures analyses of variance with Holm’s multiple comparison test (MTPJ position × ankle position) were performed. When the MTPJ was dorsiflexed at 0°, 15°, and 30°, the MVC torque of the first MTPJ when the ankle was dorsiflexed at 20° was higher than that when the ankle was plantar-flexed at 20°. However, the ankle position had no significant effect on the MVC torque of the second–fifth MTPJ. Thus, the MVC torque of the first MTPJ was more affected by the ankle position than the second–fifth MTPJs.

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In vivo and in vitro application of thin film interferometry to assess contact lens wettability

Contact Lens and Anterior Eye ◽

10.1016/j.clae.2018.04.107 ◽

2018 ◽

Vol 41 ◽

pp. S9

Author(s):

Raied Fagehi ◽

Ian Pearce ◽

Katherine Oliver ◽

Alan Tomlinson

Keyword(s):

Thin Film ◽

Contact Lens

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Nanocrystal-Loaded Micelles for the Enhanced In Vivo Circulation of Docetaxel

Molecules ◽

10.3390/molecules26154481 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4481

Author(s):

Meng Cheng ◽

Qiaoming Liu ◽

Tiantian Gan ◽

Yuanying Fang ◽

Pengfei Yue ◽

...

Keyword(s):

Thin Film ◽

Retention Time ◽

Blood Circulation ◽

Crystalline State ◽

Circulation System ◽

Particle Sizes ◽

High Pressure Homogenization ◽

Rapid Dissolution ◽

Efficient Route

Prolonging in vivo circulation has proved to be an efficient route for enhancing the therapeutic effect of rapidly metabolized drugs. In this study, we aimed to construct a nanocrystal-loaded micelles delivery system to enhance the blood circulation of docetaxel (DOC). We employed high-pressure homogenization to prepare docetaxel nanocrystals (DOC(Nc)), and then produced docetaxel nanocrystal-loaded micelles (DOC(Nc)@mPEG-PLA) by a thin-film hydration method. The particle sizes of optimized DOC(Nc), docetaxel micelles (DOC@mPEG-PLA), and DOC(Nc)@mPEG-PLA were 168.4, 36.3, and 72.5 nm, respectively. The crystallinity of docetaxel was decreased after transforming it into nanocrystals, and the crystalline state of docetaxel in micelles was amorphous. The constructed DOC(Nc)@mPEG-PLA showed good stability as its particle size showed no significant change in 7 days. Despite their rapid dissolution, docetaxel nanocrystals exhibited higher bioavailability. The micelles prolonged the retention time of docetaxel in the circulation system of rats, and DOC(Nc)@mPEG-PLA exhibited the highest retention time and bioavailability. These results reveal that constructing nanocrystal-loaded micelles may be a promising way to enhance the in vivo circulation and bioavailability of rapidly metabolized drugs such as docetaxel.

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Recovery of Aging-Related Size Increase of Skin Epithelial Cells: In vivo Mouse and In vitro Human Study

PLoS ONE ◽

10.1371/journal.pone.0122774 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0122774 ◽

Cited By ~ 4

Author(s):

Igor Sokolov ◽

Natali V. Guz ◽

Swaminathan Iyer ◽

Amy Hewitt ◽

Nina A. Sokolov ◽

...

Keyword(s):

Epithelial Cells ◽

Human Study ◽

Size Increase

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Potentials and Safety of Date Palm Fruit against Diabetes: A Critical Review

Foods ◽

10.3390/foods9111557 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1557

Author(s):

Md Al-Tareq Mia ◽

Md Golam Mosaib ◽

Md Ibrahim Khalil ◽

Md Asiful Islam ◽

Siew Hua Gan

Keyword(s):

Date Palm ◽

Antioxidant Activities ◽

Human Study ◽

Insulin Receptors ◽

Β Cells ◽

Palm Fruit ◽

Good Potential ◽

Palm Fruits

Diabetes is a chronic metabolic disorder triggered by disturbances in carbohydrate, protein, and lipid metabolisms, where either reduced secretion or sensitivity of insulin is observed coupled with poor glucose control. Date palm fruits are one of the fruits reported to have good potential in diabetes treatment due to its presence of polyphenols exerting strong antioxidant activities. Other possible mechanisms of action include the polyphenolic compounds, which can inhibit enzymes like α-amylase and α-glucosidase. Flavonoids in dates can stimulate β-cells by increasing the number of islets and β-cells, recovering endocrine pancreatic tissues, reducing β-cell apoptosis, activating insulin receptors following the increase in insulin secretion, in addition to improving diabetes-induced complications. In this review, the in vitro, in vivo, and human study-based evidence of date palm as an anti-diabetic fruit is summarised.

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Glucocorticoid-induced eosinopenia results from CXCR4-dependent bone marrow migration

Blood ◽

10.1182/blood.2020005161 ◽

2020 ◽

Vol 136 (23) ◽

pp. 2667-2678

Author(s):

So Gun Hong ◽

Noriko Sato ◽

Fanny Legrand ◽

Manasi Gadkari ◽

Michelle Makiya ◽

...

Keyword(s):

Bone Marrow ◽

Rhesus Macaques ◽

Human Study ◽

Isolation Technique ◽

Selective Blockade ◽

First Line Therapy ◽

Positron Emission ◽

Before And After ◽

Eosinophilic Disorders

Abstract Glucocorticoids are considered first-line therapy in a variety of eosinophilic disorders. They lead to a transient, profound decrease in circulating human eosinophils within hours of administration. The phenomenon of glucocorticoid-induced eosinopenia has been the basis for the use of glucocorticoids in eosinophilic disorders, and it has intrigued clinicians for 7 decades, yet its mechanism remains unexplained. To investigate, we first studied the response of circulating eosinophils to in vivo glucocorticoid administration in 3 species and found that the response in rhesus macaques, but not in mice, closely resembled that in humans. We then developed an isolation technique to purify rhesus macaque eosinophils from peripheral blood and performed live tracking of zirconium-89-oxine–labeled eosinophils by serial positron emission tomography/computed tomography imaging, before and after administration of glucocorticoids. Glucocorticoids induced rapid bone marrow homing of eosinophils. The kinetics of glucocorticoid-induced eosinopenia and bone marrow migration were consistent with those of the induction of the glucocorticoid-responsive chemokine receptor CXCR4, and selective blockade of CXCR4 reduced or eliminated the early glucocorticoid-induced reduction in blood eosinophils. Our results indicate that glucocorticoid-induced eosinopenia results from CXCR4-dependent migration of eosinophils to the bone marrow. These findings provide insight into the mechanism of action of glucocorticoids in eosinophilic disorders, with implications for the study of glucocorticoid resistance and the development of more targeted therapies. The human study was registered at ClinicalTrials.gov as #NCT02798523.

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Self-Expandable Thin Film Nitinol Endografts for Vascular Repair: Manufacturing and Short-Term Results in Swine

ASME 2009 4th Frontiers in Biomedical Devices ◽

10.1115/biomed2009-83048 ◽

2009 ◽

Author(s):

Youngjae Chun ◽

Daniel S. Levi ◽

K. P. Mohanchandra ◽

Gregory P. Carman

Keyword(s):

Thin Film ◽

Layer Growth ◽

Sputter Deposition ◽

In Vivo Studies ◽

Graft Material ◽

Vascular Repair ◽

Short Term ◽

Strain Behavior ◽

Mems Technology

A thin film nitinol covered endograft for vessel treatment was manufactured and in vivo swine testing was performed. Thin film nitinol graft material was fabricated by DC sputter deposition and stress-strain behavior and DSC characteristics were investigated. Micro size patterns were fabricated by MEMS technology in order to promote endothelial layer growth. In-vivo studies in swine were conducted to evaluate deployment, placement and patency of the implanted stent device.

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Bacterial Adhesion on Commercially Pure Titanium and Zirconium Oxide Disks: An In Vivo Human Study

Journal of Periodontology ◽

10.1902/jop.2004.75.2.292 ◽

2004 ◽

Vol 75 (2) ◽

pp. 292-296 ◽

Cited By ~ 330

Author(s):

Antonio Scarano ◽

Maurizio Piattelli ◽

Sergio Caputi ◽

Gian Antonio Favero ◽

Adriano Piattelli

Keyword(s):

Bacterial Adhesion ◽

Zirconium Oxide ◽

Human Study ◽

Pure Titanium ◽

Commercially Pure Titanium ◽

Commercially Pure

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Tolerability and preliminary efficacy of BXQ-350 for refractory solid tumors and high-grade gliomas: First-in-human, first-in-class phase I trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.3505 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 3505-3505

Author(s):

Olivier Rixe ◽

John Charles Morris ◽

Robert Wesolowski ◽

Emrullah Yilmaz ◽

Richard Curry ◽

...

Keyword(s):

Solid Tumors ◽

Dose Level ◽

Human Study ◽

Treatment Protocol ◽

High Grade Glioma ◽

Maximum Tolerated Dose ◽

High Grade ◽

Serious Adverse Events

3505 Background: BXQ-350 is a first-in-class agent comprised of Saposin C (SapC) and dioleoyl phosphatidylserine (DOPS). SapC, a multifunctional lysosomal-activator glycoprotein that preferentially interacts with tumor cell phospholipids, has demonstrated anti-tumor effects in both in vitro and in vivo preclinical models. The tolerability and preliminary efficacy of BXQ-350 in the first-in-human study are summarized here. Methods: Eighty-six refractory solid tumor (ST) or high-grade glioma (HGG) patients age ≥18 (36F:50M, age 24-81) were enrolled in a 3-part first-in-human trial (NCT02859857) from 2016-2019 and received at least one dose of BXQ-350. Doses were administered via intravenous infusion during 28-day cycles until disease progression occurred. The previously reported part 1 dose escalation portion of the study (9 HGG, 9 ST patients) established the highest planned dose of 2.4mg/kg as safe but did not identify a maximum tolerated dose. The part 2 expansion cohort treated 37 patients (18 HGG and 19 ST) and an additional part 3 cohort treated 31 ST gastrointestinal (GI) patients, both at the 2.4 mg/kg dose level. Preliminary antitumor activity was evaluated (RECISTv1.1 or RANO). Results: There were no BXQ-350-related serious adverse events, dose limiting toxicities or withdrawals with the exception of 1 allergic type reaction. Three patients (Glioblastoma, Ependymoma, Appendiceal) demonstrated a partial response per RECIST/RANO. Two HGG patients with progressive radiologic enhancement were seen to have treatment effect at surgery, and hence considered to have stable disease. Seven patients (2 HGG, 3 GI, 2 other ST) remain on study and have received treatment for 9+ to 41+ months, with 5 patients treated for > 1 year. A continuing treatment protocol is planned in order to allow these patients to remain on BXQ-350 treatment. Conclusions: BXQ-350 was well tolerated with no significant dose-limiting toxicities at the highest planed dose level. Preliminary results indicate this novel agent demonstrated possible anti-tumor activity in refractory solid tumors and HGG. Clinical trial information: NCT03967093) .

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