title: Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes.
abstract: Implantable neural electrodes must drastically improve chronic recording stability before they can be translated into long-term human clinical prosthetics. Previous studies suggest that sub-cellular sized and mechanically compliant probes may result in improved tissue integration and recording longevity. However, currently these design features are restricted by the opposing mechanical requirements needed for minimally damaging insertions. We designed a non-cytotoxic, carboxymethylcellulose (CMC) based dissolvable delivery vehicle (shuttle) to provide the mechanical support for insertion of ultra-small, ultra-compliant microfabricated neural probes. Stiff CMC-based shuttles rapidly soften immediately after being placed ∼1 mm above an open craniotomy as they absorb vapors from the brain. To address this, we developed a sophisticated targeting, high speed insertion (∼80 mm/s), and release system to implant these shuttles. After implantation, the goal is for the shuttle to dissolve away leaving only the electrodes behind. Here we show the histology of chronically implanted shuttles of large (300 μm × 125 μm) and small (100 μm × 125 μm) size at discrete time points over 12 weeks. Early time points show the CMC shuttle expanded after insertion as it absorbed moisture from the brain and slowly dissolved. At later time points neuronal cell bodies populate regions within the original shuttle tract. The large CMC shuttles show that the CMC expansion can cause extended secondary damage. On the other hand, the smaller CMC shuttles show limited secondary damage, wound closure by 4 weeks, absence of activated microglia at 12 weeks, as well as evidence suggesting neural regeneration at the implant site. This shuttle, therefore, shows great promise facilitating the implantation of nontraditional ultra-small, and ultra-compliant probes.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neural Basis of Cognition, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA. Electronic address: tdk18@pitt.edu.
authors.forename: Takashi D Y
authors.initials: TD
authors.lastname: Kozai
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Zhannetta
authors.initials: Z
authors.lastname: Gugel
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Electrical & Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gilgunn
authors.affiliation: Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Khilwani
authors.affiliation: Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: O Burak
authors.initials: OB
authors.lastname: Ozdoganlar
authors.affiliation: Department of Electrical & Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Fedder
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Department of Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Weber
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neural Basis of Cognition, Pittsburgh, PA, USA; McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA. Electronic address: xic11@pitt.edu.
authors.forename: X Tracy
authors.initials: XT
authors.lastname: Cui
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D004567:Electrodes, Implanted; D004867:Equipment Design; D008297:Male; D009339:Needles; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D002266:Carboxymethylcellulose Sodium
keywords: BBB injury; Drug delivery; Flexible electrode; Neural regeneration; Wireless probe delivery vehicle; Wound healing