Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices

Intracortical neural probes are both a powerful tool in basic neuroscience studies of brain function and a critical component of brain computer interfaces (BCIs) designed to restore function to paralyzed patients. Intracortical neural probes can be used both to detect neural activity at single unit...

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Main Authors: Youjoung Kim, Natalie N. Mueller, William E. Schwartzman, Danielle Sarno, Reagan Wynder, George F. Hoeferlin, Kaela Gisser, Jeffrey R. Capadona, Allison Hess-Dunning
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Micromachines
Subjects:
Online Access:https://www.mdpi.com/2072-666X/14/5/1015
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author Youjoung Kim
Natalie N. Mueller
William E. Schwartzman
Danielle Sarno
Reagan Wynder
George F. Hoeferlin
Kaela Gisser
Jeffrey R. Capadona
Allison Hess-Dunning
author_facet Youjoung Kim
Natalie N. Mueller
William E. Schwartzman
Danielle Sarno
Reagan Wynder
George F. Hoeferlin
Kaela Gisser
Jeffrey R. Capadona
Allison Hess-Dunning
author_sort Youjoung Kim
collection DOAJ
description Intracortical neural probes are both a powerful tool in basic neuroscience studies of brain function and a critical component of brain computer interfaces (BCIs) designed to restore function to paralyzed patients. Intracortical neural probes can be used both to detect neural activity at single unit resolution and to stimulate small populations of neurons with high resolution. Unfortunately, intracortical neural probes tend to fail at chronic timepoints in large part due to the neuroinflammatory response that follows implantation and persistent dwelling in the cortex. Many promising approaches are under development to circumvent the inflammatory response, including the development of less inflammatory materials/device designs and the delivery of antioxidant or anti-inflammatory therapies. Here, we report on our recent efforts to integrate the neuroprotective effects of both a dynamically softening polymer substrate designed to minimize tissue strain and localized drug delivery at the intracortical neural probe/tissue interface through the incorporation of microfluidic channels within the probe. The fabrication process and device design were both optimized with respect to the resulting device mechanical properties, stability, and microfluidic functionality. The optimized devices were successfully able to deliver an antioxidant solution throughout a six-week in vivo rat study. Histological data indicated that a multi-outlet design was most effective at reducing markers of inflammation. The ability to reduce inflammation through a combined approach of drug delivery and soft materials as a platform technology allows future studies to explore additional therapeutics to further enhance intracortical neural probes performance and longevity for clinical applications.
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spelling doaj.art-a06385fba39a4d4b9f6c9b088bb8b3252023-11-18T02:30:30ZengMDPI AGMicromachines2072-666X2023-05-01145101510.3390/mi14051015Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical DevicesYoujoung Kim0Natalie N. Mueller1William E. Schwartzman2Danielle Sarno3Reagan Wynder4George F. Hoeferlin5Kaela Gisser6Jeffrey R. Capadona7Allison Hess-Dunning8Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USADepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USAIntracortical neural probes are both a powerful tool in basic neuroscience studies of brain function and a critical component of brain computer interfaces (BCIs) designed to restore function to paralyzed patients. Intracortical neural probes can be used both to detect neural activity at single unit resolution and to stimulate small populations of neurons with high resolution. Unfortunately, intracortical neural probes tend to fail at chronic timepoints in large part due to the neuroinflammatory response that follows implantation and persistent dwelling in the cortex. Many promising approaches are under development to circumvent the inflammatory response, including the development of less inflammatory materials/device designs and the delivery of antioxidant or anti-inflammatory therapies. Here, we report on our recent efforts to integrate the neuroprotective effects of both a dynamically softening polymer substrate designed to minimize tissue strain and localized drug delivery at the intracortical neural probe/tissue interface through the incorporation of microfluidic channels within the probe. The fabrication process and device design were both optimized with respect to the resulting device mechanical properties, stability, and microfluidic functionality. The optimized devices were successfully able to deliver an antioxidant solution throughout a six-week in vivo rat study. Histological data indicated that a multi-outlet design was most effective at reducing markers of inflammation. The ability to reduce inflammation through a combined approach of drug delivery and soft materials as a platform technology allows future studies to explore additional therapeutics to further enhance intracortical neural probes performance and longevity for clinical applications.https://www.mdpi.com/2072-666X/14/5/1015microfluidicpolymermechanically adaptiveneural interfacemicrofabricationdrug delivery
spellingShingle Youjoung Kim
Natalie N. Mueller
William E. Schwartzman
Danielle Sarno
Reagan Wynder
George F. Hoeferlin
Kaela Gisser
Jeffrey R. Capadona
Allison Hess-Dunning
Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices
Micromachines
microfluidic
polymer
mechanically adaptive
neural interface
microfabrication
drug delivery
title Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices
title_full Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices
title_fullStr Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices
title_full_unstemmed Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices
title_short Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices
title_sort fabrication methods and chronic in vivo validation of mechanically adaptive microfluidic intracortical devices
topic microfluidic
polymer
mechanically adaptive
neural interface
microfabrication
drug delivery
url https://www.mdpi.com/2072-666X/14/5/1015
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