The Miniature Pig: A Large Animal Model for Cochlear Implant Research

Summary

Miniature pigs (mini-pigs) are an ideal large animal model for research into cochlear implants. Cochlear implantation surgery in mini-pigs can be utilized to provide initial evidence of the safety and potential performance of novel electrode arrays and surgical approaches in a living system similar to human beings.

Abstract

Cochlear implants (CI) are the most effective method to treat people with severe-to-profound sensorineural hearing loss. Although CIs are used worldwide, no standard model exists for investigating the electrophysiology and histopathology in patients or animal models with a CI or for evaluating new models of electrode arrays. A large animal model with cochlea characteristics similar to those of humans may provide a research and evaluation platform for advanced and modified arrays before their use in humans.

To this end, we established standard CI methods with Bama mini-pigs, whose inner ear anatomy is highly similar to that of humans. Arrays designed for human use were implanted into the mini pig cochlea through a round window membrane, and a surgical approach followed that was similar to that used for human CI recipients. Array insertion was followed by evoked compound action potential (ECAP) measurements to evaluate the function of the auditory nerve. This study describes the preparation of the animal, surgical steps, array insertion, and intraoperative electrophysiological measurements.

The results indicated that the same CI used for humans could be easily implanted in mini-pigs via a standardized surgical approach and yielded similar electrophysiological outcomes as measured in human CI recipients. Mini-pigs could be a valuable animal model to provide initial evidence of the safety and potential performance of novel electrode arrays and surgical approaches before applying them to human beings.

Introduction

According to the World Health Organization (WHO), over 1 billion people are at risk of hearing loss globally, and it is estimated that, by 2050, one out of four people will suffer hearing loss¹. Over the last 2 decades, CIs have been the most effective intervention for people with permanent severe and profound sensorineural hearing loss (SNHL). A CI converts physical signals of sound into bioelectrical signals that stimulate the spiral ganglion neurons (SGNs), bypassing hair cells. Over time, the indications for a CI have been broadened so that they now include people with residual hearing, unilateral hearing loss, and very old or young people<....

Protocol

All procedures and animal surgeries were conducted according to the guidelines of the Ethics Committee of the PLA General Hospital and were approved.

1. Anesthesia and surgical preparation

1. Inject the pig (male, 2 months old, 5 kg) muscularly with tiletamine and zolazepam with a dosage of 10-15 mg/kg and intubate it with a 5.5-French endotracheal tube. Maintain anesthesia by ventilator-assisted respiration with isofluorane inhalation. Monitor the oxygen saturation (>90%), breathing (15-20/min), and heart rate (60-120 beats/min) using the pulse oximetry clamp of an ECG monitor, which is connected to the pig....

Results

The integrity (Figure 4A) and impedances (Figure 4B) of the CI were confirmed by MAESTRO Software. ECAP results showed that all 12 electrodes demonstrated good neural responses (Figure 4C), meaning the electrode array was well attached to the cochlear axis and stimulated the auditory nerve. Figure 5 demonstrates postoperative 3D reconstructed electrode coils in the right cochlea. The array did not .......

Discussion

Around 15% of the world's population have some degree of hearing loss, and over 5% have disabling hearing loss²¹. CI provision is the most efficient treatment for both adult and pediatric patients with severe and profound sensorineural hearing loss. As the first successful implantable cranial nerve stimulator, over the past 2 decades, CIs have offered thousands of people with hearing loss the opportunity to return to the world of sound and (re)integrate into mainstream society. Even though CIs are.......

Materials

Name	Company	Catalog Number	Comments
0.5 mm diamond burr
1 mm diamond burr
5 mm diamond burr
2-0 suture silk
3D Slicer image computing platform			3D reconstruction of CT image
Alcohol
Bipolar cautery
Bipolar electrocoagulation			Stop bleeding
CI designed for human use (CONCERTO FLEX28)	MED-EL	Concerto F28
Dressing forceps
ECG monitor
Iodine tincture
Isoflurane			3.6 mL/h
Laryngoscope
MAESTRO Software	MED-EL		Measure ECAP responses
Micro forceps
Micro spatula
Mosquito forceps
Needle holder
Needle probe
Negative pressure suction device
Otological surgical instruments
Respiratory Anesthesia Machine
Scalpel with blade No. 15
Scissors
Shaver
Stimulation device (MAX Programming Interface)	MED-EL		Measure ECAP responses
Surgery microscope	Leica
Surgical drill
Surgical Power Device
Tiletamine and zolazepan			10-15 mg/kg
Tissue forceps
Trachea cannula