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

2019 ◽  
Author(s):  
Justin C. Burrell ◽  
Kevin D. Browne ◽  
John L. Dutton ◽  
Suradip Das ◽  
Daniel P. Brown ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Surgical Approach ◽  
Peripheral Nerve Injury ◽  
Peroneal Nerve ◽  
Porcine Model ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Common Peroneal Nerve ◽  
Nerve Autograft

AbstractApproximately 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.

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

Neurosurgery ◽  
2020 ◽  
Vol 87 (4) ◽  
pp. 833-846 ◽  
Author(s):  
Justin C Burrell ◽  
Kevin D Browne ◽  
John L Dutton ◽  
Franco A Laimo ◽  
Suradip Das ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Surgical Approach ◽  
Peripheral Nerve Injury ◽  
Peroneal Nerve ◽  
Porcine Model ◽  
Common Peroneal Nerve ◽  
Preclinical Model ◽  
Distal Stump

Abstract BACKGROUND Millions of Americans experience residual deficits from traumatic peripheral nerve injury (PNI). Despite advancements in surgical technique, repair typically results in poor functional outcomes due to prolonged periods of denervation resulting from long regenerative distances coupled with slow rates of axonal regeneration. Novel surgical solutions require valid preclinical models that adequately replicate the key challenges of clinical PNI. OBJECTIVE To develop a preclinical model of PNI in swine that addresses 2 challenging, clinically relevant PNI scenarios: long segmental defects (≥5 cm) and ultra-long regenerative distances (20-27 cm). Thus, we aim to demonstrate that a porcine model of major PNI is suitable as a potential framework to evaluate novel regenerative strategies prior to clinical deployment. METHODS A 5-cm-long common peroneal nerve or deep peroneal nerve injury was repaired using a saphenous nerve or sural nerve autograft, respectively. Histological and electrophysiological assessments were performed at 9 to 12 mo post repair to evaluate nerve regeneration and functional recovery. Relevant anatomy, surgical approach, and functional/histological outcomes were characterized for both repair techniques. RESULTS Axons regenerated across the repair zone and were identified in the distal stump. Electrophysiological recordings confirmed these findings and suggested regenerating axons reinnervated target muscles. CONCLUSION The models presented herein provide opportunities to investigate peripheral nerve regeneration using different nerves tailored for specific mechanisms of interest, such as nerve modality (motor, sensory, and mixed fiber composition), injury length (short/long gap), and total regenerative distance (proximal/distal injury).

scholarly journals Establishment of a Sheep Model for Hind Limb Peripheral Nerve Injury: Common Peroneal Nerve

2021 ◽  
Vol 22 (3) ◽  
pp. 1401
Author(s):  
Rui D. Alvites ◽  
Mariana V. Branquinho ◽  
Ana C. Sousa ◽  
Federica Zen ◽  
Monica Maurina ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Peroneal Nerve ◽  
Common Peroneal Nerve ◽  
Small Sample ◽  
Therapeutic Options ◽  
Nerve Injuries ◽  
Sheep Model ◽  
The Common

Thousands of people worldwide suffer from peripheral nerve injuries and must deal daily with the resulting physiological and functional deficits. Recent advances in this field are still insufficient to guarantee adequate outcomes, and the development of new and compelling therapeutic options require the use of valid preclinical models that effectively replicate the characteristics and challenges associated with these injuries in humans. In this study, we established a sheep model for common peroneal nerve injuries that can be applied in preclinical research with the advantages associated with the use of large animal models. The anatomy of the common peroneal nerve and topographically related nerves, the functional consequences of its injury and a neurological examination directed at this nerve have been described. Furthermore, the surgical protocol for accessing the common peroneal nerve, the induction of different types of nerve damage and the application of possible therapeutic options were described. Finally, a preliminary morphological and stereological study was carried out to establish control values for the healthy common peroneal nerves regarding this animal model and to identify preliminary differences between therapeutic methods. This study allowed to define the described lateral incision as the best to access the common peroneal nerve, besides establishing 12 and 24 weeks as the minimum periods to study lesions of axonotmesis and neurotmesis, respectively, in this specie. The post-mortem evaluation of the harvested nerves allowed to register stereological values for healthy common peroneal nerves to be used as controls in future studies, and to establish preliminary values associated with the therapeutic performance of the different applied options, although limited by a small sample size, thus requiring further validation studies. Finally, this study demonstrated that the sheep is a valid model of peripheral nerve injury to be used in pre-clinical and translational works and to evaluate the efficacy and safety of nerve injury therapeutic options before its clinical application in humans and veterinary patients.

scholarly journals Establishment of a Sheep Model for Hind limb Peripheral Nerve Injury: Common Peroneal Nerve

2020 ◽  
Author(s):  
Rui D. Alvites ◽  
Mariana V. Branquinho ◽  
Ana Catarina Sousa ◽  
Federica Zen ◽  
Monica Maurina ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Peroneal Nerve ◽  
Hind Limb ◽  
Common Peroneal Nerve ◽  
Therapeutic Options ◽  
Large Animal ◽  
Sheep Model ◽  
The Common

Thousands of people worldwide suffer from injuries in the peripheral nerve and deal daily with the resulting physiological and functional deficits. Recent advances in this field are still insufficient to guarantee effective outcomes, and the development of new and effective therapeutic options requires the use of valid preclinical models that effectively replicate the characteristics and challenges associated with these injuries in humans. In this study, we established a sheep model for common peroneal nerve injuries that can be applied in preclinical research with the advantages associated with the use of large animal models. In an integrative way, this article includes a detailed description of the anatomy and functionality of the peripheral nerves of sheep’s hind limb, the surgical protocol for accessing the common peroneal nerve, the induction of different types of nerve damage and the application of possible therapeutic options. A neurological exam protocol directed to the common peroneal nerve was also established, allowing to identify the changes and deficits related with the nerve injury and to evaluate the functional progression over time. Finally, a preliminary stereological study was carried out to establish control values for the healthy peroneal common nerves of this model and to identify preliminary differences between therapeutic methods. The ultimate goal is to demonstrate that sheep is a valid model of peripheral nerve injury to be used in pre-clinical and translational works and to evaluate the efficacy and safety of nerve injury therapeutic options before its clinical application in human and veterinary patients.

scholarly journals Polyethylene Glycol Treatment for Peripheral Nerve Repair in Preclinical Models

2021 ◽  
Vol 6 (1) ◽  
pp. 21-25
Author(s):  
Davis B. Rippee ◽  
Gabriella E. Glassman ◽  
Sara C. Chaker ◽  
Patrick E. Assi ◽  
Jennifer Black ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Preclinical Models ◽  
Peripheral Nerve Repair ◽  
Peg Treatment

Introduction: Peripheral nerve injuries commonly result from trauma and can lead to devastating loss of sensory and motor function. A novel strategy to improve peripheral nerve regeneration is a chemical fusogen known as polyethylene glycol (PEG). Several animal studies have illustrated PEG’s potential to help prevent axon loss after peripheral nerve injury. However, the relative rate of success and potential complications of these studies have not been definitively shown in the literature. The purpose of this systematic review is to evaluate the literature regarding the success of PEG adjunct treatment after peripheral nerve injury in preclinical models. Materials and Methods: The MEDLINE database was queried using the PubMed search engine with the following keywords and phrases: “polyethylene glycol” OR “PEG” AND “nerve” AND “fusion”. All resulting articles were screened by two reviewers. Animal type, nerve type, injury type, type(s) of analyses, and overall superiority of outcomes were assessed. Results: One-hundred and seventy-nine articles were identified, and thirteen studies remained after the application of inclusion and exclusion criteria. Twelve of the thirteen studies utilized rats as the preclinical model, while one utilized a guinea pig. Superiority of peripheral nerve repair outcomes with adjunct PEG treatment compared to a control group was reported in eleven of thirteen studies. Conclusions: The majority of studies reported positive outcomes when using PEG; this indicates that PEG treatment has the potential to enhance peripheral nerve regeneration after injury. However, the results of some of these studies indicated several uncertainties that need to be addressed in future studies. These preclinical models may help guide clinicians regarding the use of PEG treatment in peripheral nerve repair.

scholarly journals A study on graphene composites for peripheral nerve injury repair under electrical stimulation

RSC Advances ◽  
2019 ◽  
Vol 9 (49) ◽  
pp. 28627-28635 ◽  
Author(s):  
Zhiqiang Huang ◽  
Zhenzhao Guo ◽  
Manman Sun ◽  
Shaomao Fang ◽  
Hong Li
Keyword(s):  
Electrical Stimulation ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Nerve Repair ◽  
Effective Alternative ◽  
Peripheral Nerve Repair ◽  
Injury Repair

Electrical stimulation (ES) provides an effective alternative to peripheral nerve repair via conductive scaffolds.

FLEXOR TENDON AND PERIPHERAL NERVE REPAIR

Hand Surgery ◽  
2002 ◽  
Vol 07 (01) ◽  
pp. 83-100 ◽  
Author(s):  
Judith A. Bell Krotoski
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Flexor Tendon ◽  
Nerve Repair ◽  
Hand Function ◽  
Tendon Injury ◽  
Finger Movement ◽  
Flexor Tendon Injury ◽  
Direct Injury

Any restoration of hand function following tendon and nerve injury has to include the repair or replacement of the hand's ability to perform a great many tasks. It is hard at first to appreciate fully the loss that occurs with flexor tendon injury. With loss of flexor tendons operating at the fingers or thumb, they cannot be fully closed and the hand is impaired for grasp and release as it interfaces with objects. But, sensibility can also be compromised from tendon injury even without direct injury to nerve, as object recognition in the absence of vision requires finger movement. When peripheral nerve injury is combined with flexor tendon injury, sensibility is directly impaired. There is a loss in the sense of finger or thumb position, pain, temperature, and touch/pressure recognition, in addition to the tendon injury.

scholarly journals Nerve Suture Combined With ADSCs Injection Under Real-Time and Dynamic NIR-II Fluorescence Imaging in Peripheral Nerve Regeneration in vivo

2021 ◽  
Vol 9 ◽  
Author(s):  
Shixian Dong ◽  
Sijia Feng ◽  
Yuzhou Chen ◽  
Mo Chen ◽  
Yimeng Yang ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Real Time ◽  
Fluorescence Imaging ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Peripheral Nerve Regeneration ◽  
Post Injection ◽  
Nerve Suture

Peripheral nerve injury gives rise to devastating conditions including neural dysfunction, unbearable pain and even paralysis. The therapeutic effect of current treatment for peripheral nerve injury is unsatisfactory, resulting in slow nerve regeneration and incomplete recovery of neural function. In this study, nerve suture combined with ADSCs injection was adopted in rat model of sciatic nerve injury. Under real-time visualization of the injected cells with the guidance of NIR-II fluorescence imaging in vivo, a spatio-temporal map displaying cell migration from the proximal injection site (0 day post-injection) of the nerve to the sutured site (7 days post-injection), and then to the distal section (14 days post-injection) was demonstrated. Furthermore, the results of electromyography and mechanical pain threshold indicated nerve regeneration and functional recovery after the combined therapy. Therefore, in the current study, the observed ADSCs migration in vivo, electrophysiological examination results and pathological changes all provided robust evidence for the efficacy of the applied treatment. Our approach of nerve suture combined with ADSCs injection in treating peripheral nerve injury under real-time NIR-II imaging monitoring in vivo added novel insights into the treatment for peripheral nerve injury, thus further enhancing in-depth understanding of peripheral nerve regeneration and the mechanism behind.

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