title: Microchannel-based regenerative scaffold for chronic peripheral nerve interfacing in amputees.
abstract: Neurally controlled prosthetics that cosmetically and functionally mimic amputated limbs remain a clinical need because state of the art neural prosthetics only provide a fraction of a natural limb's functionality. Here, we report on the fabrication and capability of polydimethylsiloxane (PDMS) and epoxy-based SU-8 photoresist microchannel scaffolds to serve as viable constructs for peripheral nerve interfacing through in vitro and in vivo studies in a sciatic nerve amputee model where the nerve lacks distal reinnervation targets. These studies showed microchannels with 100 μm × 100 μm cross-sectional areas support and direct the regeneration/migration of axons, Schwann cells, and fibroblasts through the microchannels with space available for future maturation of the axons. Investigation of the nerve in the distal segment, past the scaffold, showed a high degree of organization, adoption of the microchannel architecture forming 'microchannel fascicles', reformation of endoneurial tubes and axon myelination, and a lack of aberrant and unorganized growth that might be characteristic of neuroma formation. Separate chronic terminal in vivo electrophysiology studies utilizing the microchannel scaffolds with permanently integrated microwire electrodes were conducted to evaluate interfacing capabilities. In all devices a variety of spontaneous, sensory evoked and electrically evoked single and multi-unit action potentials were recorded after five months of implantation. Together, these findings suggest that microchannel scaffolds are well suited for chronic implantation and peripheral nerve interfacing to promote organized nerve regeneration that lends itself well to stable interfaces. Thus this study establishes the basis for the advanced fabrication of large-electrode count, wireless microchannel devices that are an important step towards highly functional, bi-directional peripheral nerve interfaces.
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
authors.forename: Akhil
authors.initials: A
authors.lastname: Srinivasan
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
authors.forename: Mayank
authors.initials: M
authors.lastname: Tahilramani
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Bentley
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Russell K
authors.initials: RK
authors.lastname: Gore
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Millard
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
authors.forename: Vivek J
authors.initials: VJ
authors.lastname: Mukhatyar
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
authors.forename: Anish
authors.initials: A
authors.lastname: Joseph
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
authors.forename: Adel S
authors.initials: AS
authors.lastname: Haque
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.
authors.forename: Garrett B
authors.initials: GB
authors.lastname: Stanley
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Arthur W
authors.initials: AW
authors.lastname: English
authors.affiliation: Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA. Electronic address: ravi@gatech.edu.
authors.forename: Ravi V
authors.initials: RV
authors.lastname: Bellamkonda
mesh_terms: D000818:Animals; D051381:Rats; D000200:Action Potentials; D001369:Axons / Q000502:physiology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D005071:Evoked Potentials; D005727:Ganglia, Spinal / Q000503:physiopathology; D009416:Nerve Regeneration; D012584:Sciatic Nerve / Q000503:physiopathology; D054457:Tissue Scaffolds / Q000737:chemistry
keywords: Microchannel; Nerve guide; Nerve regeneration; Neural interfacing; Peripheral nerve interfacing; Polydimethylsiloxane