A Porcine Model of Peripheral Nerve Injury Enabling Ultra-Long Regenerative Distances: Surgical Approach, Recovery Kinetics, and Clinical Relevance

Abstract

Approximately 20 million Americans currently experience residual deficits from traumatic peripheral nerve injury. Despite recent advancements in surgical technique, peripheral nerve repair typically results in poor functional outcomes due to prolonged periods of denervation resulting from long regenerative distances coupled with relatively slow rates of axonal regeneration. Development of novel surgical solutions requires valid preclinical models that adequately replicate the key challenges of clinical peripheral nerve injury. Our team has developed a porcine model using Yucatan minipigs that provides an opportunity to investigate peripheral nerve regeneration using different nerves tailored for a specific mechanism of interest, such as (1) nerve modality: motor, sensory, and mixed-modality; (2) injury length: short versus long gap; and (3) total regenerative distance: proximal versus distal injury. Here, we describe a comprehensive porcine model of two challenging clinically relevant procedures for repair of long segmental lesions ([≥] 5 cm) - the deep peroneal nerve repaired using a sural nerve autograft and the common peroneal nerve repaired using a saphenous nerve autograft - each featuring ultra-long total regenerative distances (up to 20 cm and 27 cm, respectively) to reach distal targets. This paper includes a detailed characterization of the relevant anatomy, surgical approach/technique, functional/electrophysiological outcomes, and nerve morphometry for baseline and autograft repaired nerves. These porcine models of major peripheral nerve injury are suitable as preclinical, translatable models for evaluating the efficacy, safety, and tolerability of next-generation artificial nerve grafts prior to clinical deployment.