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