title: Behavioral and cellular consequences of high-electrode count Utah Arrays chronically implanted in rat sciatic nerve.
abstract: OBJECTIVE
  Before peripheral nerve electrodes can be used for the restoration of sensory and motor functions in patients with neurological disorders, the behavioral and histological consequences of these devices must be investigated. These indices of biocompatibility can be defined in terms of desired functional outcomes; for example, a device may be considered for use as a therapeutic intervention if the implanted subject retains functional neurons post-implantation even in the presence of a foreign body response. The consequences of an indwelling device may remain localized to cellular responses at the device-tissue interface, such as fibrotic encapsulation of the device, or they may affect the animal more globally, such as impacting behavioral or sensorimotor functions. The objective of this study was to investigate the overall consequences of implantation of high-electrode count intrafascicular peripheral nerve arrays, High Density Utah Slanted Electrode Arrays (HD-USEAs; 25 electrodes mm(-2)).
  
  
  METHODS
  HD-USEAs were implanted in rat sciatic nerves for one and two month periods. We monitored wheel running, noxious sensory paw withdrawal reflexes, footprints, nerve morphology and macrophage presence at the tissue-device interface. In addition, we used a novel approach to contain the arrays in actively behaving animals that consisted of an organic nerve wrap. A total of 500 electrodes were implanted across all ten animals.
  
  
  RESULTS
  The results demonstrated that chronic implantation (⩽8 weeks) of HD-USEAs into peripheral nerves can evoke behavioral deficits that recover over time. Morphology of the nerve distal to the implantation site showed variable signs of nerve fiber degeneration and regeneration. Cytology adjacent to the device-tissue interface also showed a variable response, with some electrodes having many macrophages surrounding the electrodes, while other electrodes had few or no macrophages present. This variability was also seen along the length of the electrodes. Axons remained within the proximity of the electrode tips at the distances required for theoretically effective stimulation and recording (⩽100 μm).
  
  
  CONCLUSIONS
  We conclude from these studies that HD-USEAs do not cause overall global effects on the animals, at least up to the two-month period investigated here. These results demonstrate for the first time that the consequences of high-electrode count intrafascicular arrays compare with other peripheral nerve electrodes currently available for clinical or investigational neuromodulation.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, Utah, USA.
authors.forename: H A C
authors.initials: HA
authors.lastname: Wark
authors.forename: K S
authors.initials: KS
authors.lastname: Mathews
authors.forename: R A
authors.initials: RA
authors.lastname: Normann
authors.forename: E
authors.initials: E
authors.lastname: Fernandez
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D004567:Electrodes, Implanted / Q000009:adverse effects*; D005528:Foot / Q000294:innervation; D007091:Image Processing, Computer-Assisted; D008422:Materials Testing; D009412:Nerve Fibers / Q000502:physiology; D009416:Nerve Regeneration; D051381:Rats; D011921:Rats, Inbred WKY; D012018:Reflex / Q000502:physiology; D012420:Running / Q000502:physiology; D012584:Sciatic Nerve / Q000502:physiology*