The Muscle Cuff Regenerative Peripheral Nerve Interface for the Amplification of Intact Peripheral Nerve Signals

Summary

This manuscript provides an innovative method for developing a biologic peripheral nerve interface termed the Muscle Cuff Regenerative Peripheral Nerve Interface (MC-RPNI). This surgical construct can amplify its associated peripheral nerve's motor efferent signals to facilitate accurate detection of motor intent and the potential control of exoskeleton devices.

Abstract

Robotic exoskeletons have gained recent acclaim within the field of rehabilitative medicine as a promising modality for functional restoration for those individuals with extremity weakness. However, their use remains largely confined to research institutions, frequently operating as a means of static extremity support as motor detection methods remain unreliable. Peripheral nerve interfaces have arisen as a potential solution to this shortcoming; however, due to their inherently small amplitudes, these signals can be difficult to differentiate from background noise, lowering their overall motor detection accuracy. As current interfaces rely on abiotic materials, inherent material breakdown can occur alongside foreign body tissue reaction over time, further impacting their accuracy. The Muscle Cuff Regenerative Peripheral Nerve Interface (MC-RPNI) was designed to overcome these noted complications. Consisting of a segment of free muscle graft secured circumferentially to an intact peripheral nerve, the construct regenerates and becomes reinnervated by the contained nerve over time. In rats, this construct has demonstrated the ability to amplify a peripheral nerve's motor efferent action potentials up to 100 times the normal value through the generation of compound muscle action potentials (CMAPs). This signal amplification facilitates high accuracy detection of motor intent, potentially enabling reliable utilization of exoskeleton devices.

Introduction

In the United States alone, approximately 130 million people are affected by neuromuscular and musculoskeletal disorders, resulting in over $800 billion in annual economic impact^1,2. This group of disorders is typically secondary to pathology within the nervous systems, at the neuromuscular junction, or within the muscle itself³. Despite the variety of pathologic origins, the majority share some degree of extremity weakness^1,3. Unfortunately, this weakness is often permanent given the limitations in neural and muscle tissue rege....

Protocol

All animal procedures and experiments were carried out with the approval of the University of Michigan's Institutional Care and Use of Animals Committee (IACUC). Male and female Fischer F344 and Lewis rats (~200-300 g) at 3-6 months of age are most frequently utilized in experiments, but any strain can theoretically be utilized. If utilizing donor rats instead of autologous muscle grafts, donor rats must be isogenic to the experimental strain. Rats are allowed free access to food and water both pre- and post-operatively. Following terminal endpoint evaluations, euthanasia is performed under deep anesthesia with intra-cardiac potassium chloride injection followed b....

Results

MC-RPNI surgical fabrication is considered a peri-operative failure if rats do not survive emergence from surgical anesthesia or develop an infection within a week of the operation. Previous research has indicated a 3 month maturation period will result in reliable signal amplification from this constructs^42,45,48,49. At that time or thereafter, surgical exposure of the constructs and evaluatio.......

Discussion

The MC-RPNI is a novel construct that allows for amplification of an intact, peripheral motor nerve's efferent action potentials in order to accurately control an exoskeleton device. Specifically, the MC-RPNI confers a particular benefit to those individuals with extremity weakness caused by significant muscle disease and/or absence of muscle where EMG signals cannot be recorded. Reducing already compromised muscle function would be devastating in this population; however, the MC-RPNI has the ability to provide this .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
#15 Scalpel	Aspen Surgical, Inc	Ref 371115	Rib-Back Carbon Steel Surgical Blades (#15)
2-N-thin film load cell (S100)	Strain Measurement Devices, Inc	SMD100-0002	Measures force generated by the attached muscle
4-0 Chromic Suture	Ethicon	SKU# 1654G	P-3 Reverse Cutting Needle
5-0 Chromic Suture	Ethicon	SKU# 687G	P-3 Reverse Cutting Needle
8-0 Monofilament Suture	AROSurgical	T06A08N14-13	Black polyamide monofilament suture on a threaded tapered needle
Experimental Rats	Envigo	F344-NH-sd	Rats are Fischer F344 Strain
Fine Forceps - mirror finish	Fine Science Tools	11413-11	Fine tipped forceps with mirror finish ideal for handling delicate structures like nerves
Fluriso (Isofluorane)	VetOne	13985-528-40	Inhalational Anesthetic
Force Measurement Jig	Red Rock	n/a	Custom designed force measurement jig that allows for immobilization of hindlimb to allow for accurate muscle force recording
MATLAB software	Mathworks, Inc	PR-MATLAB-MU-MW-707-NNU	Calculates active force for each recorded force trace from passive and total force measurements
Nicolet Viasys EMG EP System	Nicolet	MFI-NCL-VIKING-SELECT-2CH-EMG	Portable EMG and nerve signal recording system capable of simultaneous 2 channel recordings from nerve and/or muscle
Oxygen	Cryogenic Gases	UN1072	Standard medical grade oxygen canisters
Potassium Chloride	APP Pharmaceuticals	63323-965-20	Injectable form, 2 mEq/mL
Povidone Iodine USP	MediChoice	65517-0009-1	10% Topical Solution, can use one bottle for multiple surgical preps
Puralube Vet Opthalmic Ointment	Dechra	17033-211-38	Corneal protective ointment for use during procedure
Rimadyl (Caprofen)	Zoetis, Inc.	NADA# 141-199	Injectable form, 50 mg/mL
Stereo Microscope	Leica	Model M60	User can adjust magnification to their preference
Surgical Instruments	Fine Science Tools	Various	User can choose instruments according to personal preference or from what is currently available in their lab
Triple Antibiotic Ointment	MediChoice	39892-0830-2	Ointment comes in sterile, disposable packets
Vannas Spring Scissors - 2mm cutting edge	Fine Science Tools	15000-04	Curved micro-dissection scissors used to perform the epineurial window
VaporStick 3	Surgivet	V7015	Anesthesia tower with space for isofluorane and oxygen canister
Webcol Alcohol Prep	Coviden	Ref 6818	Alcohol prep wipes; use a new wipe for each prep