Download - Sigma xi nerve viability presentation
Effect of PEDOT-Coated Electrodes on Nerve Viability in Regenerative Peripheral Nerve Interfaces
Presenter: Jeffrey F. Friedman, BSE
Faculty Mentor: Melanie G. Urbanchek, PhD
Section of Plastic and Reconstructive Surgery University of Michigan, Ann Arbor, MI
Advancements in Prosthetic Devices
1964 Present
Development Challenges
• Weight of the prosthesis
• Power consumption
• High-fidelity, volitional control
of complex movements
Regenerative Peripheral Nerve Interface (RPNI)
Free Muscle
Peripheral Nerve
Electrode
Small Intestinal
Submucosa (SIS)
Construction of the RPNI in a Rat Model
• Target muscle is exposed and
denervated, attachments are severed
• End of transected peripheral nerve is
sutured into the free muscle
• Electrode placed on surface of the
muscle opposite side of nerve
implantation
Advantages of the RPNI
• Increased signal-to-noise ratio
• Confirmed long-term viability of RPNI
construct and signal quality
• Stable measurements through 7-month study
• Consistent response to volitional
innervation
• Avoidance of nerve injury due to
electrode implantation
Stainless Steel vs. PEDOT-Coated Electrodes
Stainless Steel (SS)
Electrode
PEDOT-Coated
Electrode
PEDOT-Coated Electrodes• PEDOT = Poly(3,4-ethylenedioxythiophene)
conductive polymer
• Increases signal conduction compared to
SS electrodes
• PEDOT flaking has been observed during
long-term viability studies
Research Question
Does PEDOT flaking or leeching negatively
affect peripheral nerve viability and
reinnervation of the free muscle transfer?
Experimental Set-Up• Analyzed data from previous studies
using inclusion criteria:
• RPNI constructed from extensor digitorum longus
(EDL) muscle and the common peroneal nerve
• PEDOT and/or SS electrodes used in construction
• Construct wrapped in SIS
• Nerve histology and signal amplitude data
Rat leg RPNI in vivo
SS or PEDOT
Electrode
Common
Peroneal
Nerve
EDL
Electrophysiological Testing• Common peroneal nerve stimulated
Electromyographic signals recorded with
needle electrodes inserted into the RPNI
• Proximal stimulation
• RPNI signal, the Compound Muscle Action
Potential (CMAP), recorded
• Stimulus increased incrementally to identify
maximum CMAP
Nerve Histology and Morphometry Measurements• Tissues harvested at time of sacrifice
following final electrophysiological testing
• Measurements completed by Washington
University collaborator:
• Toluidine blue staining of EDL muscle cross
sections and peroneal nerve cross sections
• Nerve morphometry counts and profiles
PEDOT RPNI
Results: Peroneal Nerve Staining
Similar histology between nerves with comparable myelination, nerve
fiber size, axon size, and distribution. Increased debris observed in
PEDOT RPNIs.
SS RPNI
20.00 µm
Myelin Axoplasm Myelin Axoplasm
Results: Body Mass
360
370
380
390
400
410
420
430
440
450
Bo
dy
Ma
ss (
g)
SS RPNI
PEDOT RPNI
Rats in both groups gained weight throughout the study.
Weights at time of sacrifice were similar between groups.
Results: Total Number of Myelinated Fibers
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
Tota
l N
um
be
r o
f
Mye
lin
ate
dN
erv
e F
ibe
rs
SS RPNI
PEDOT RPNI
The total number of myelinated fibers observed in each group were
similar. Counts were taken from 7 random high power fields of nerve
cross-sections. The mean of these 7 cross-sections for all rats were
averaged, resulting in the large standard deviations.
Results: Nerve Morphometry
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
SS RPNI
PEDOT RPNI
Axon: Myelin Ratio G-Ratio
Axon-to-Myelin ratio compares relative myelin thickness to axoplasm
thickness. G-ratio compares axoplasm diameter to total nerve diameter.
Both measures are descriptive of nerve insulation and conduction
characteristics.
Results SS PEDOT
Measure Mean ± SD Mean ± SD
Myelinated Nerve Fiber
Density (Nerve/µm2)26,400 15,500 25,700 14,100
Cross-Sectional Area of
Nerve (µm2)153,100 60,000 176,600 21,800
Percent Nerve (%) 47 12 40 2
Similar myelinated nerve fiber density and cross-sectional area of nerve
observed in both SS and PEDOT RPNIs. Large standard deviations
again due to sampling. The higher percent nerve observed in SS RPNIs
is not statistically significant.
Results: Electrophysiological Testing
0
5
10
15
20
25
30
SS RPNI (N=8)
PEDOT RPNI (N=4)
CMAP (mV) Area Under CMAP (mVms)
Conduction
Velocity (m/s)
* ** ***
* = P<0.05
* = P<0.01
* = P<0.001
PEDOT coated electrodes show increased (better) CMAP and area
under CMAP when compared with the sensed values of the SS
electrode. This difference indicate the PEDOT coating on electrodes
improves recording capability.
Summary of Results
• Nerve histology and morphometry
measures are not different between
RPNIs with SS electrodes and PEDOT
coated SS electrodes
• A coating of PEDOT on electrodes
increases RPNI signal conduction
Conclusions
• In a rat model, at 7 months post RPNI
implantation
• PEDOT conductive polymer does not alter
nerve viability for reinnervating
denervated muscle
• PEDOT is biocompatible as an in vivo
epimysial electrode coating
Acknowledgements • Melanie Urbanchek, PhD
• Nick Langhals, PhD
• Paul Cederna, MD
• Theodore Kung, MD
• Peter Washabaugh
• The Neuromuscular Team
• David C Martin, PhD, University of Delaware
• Phillip Johnson, PhD, Washington University
Thank You