Justin C Burrell1,2,3, Kevin D Browne1,2, John L Dutton1, Franco A Laimo1,2, Suradip Das1,2, Daniel P Brown1,2, Sanford Roberts1,2, Dmitriy Petrov1,2, Zarina Ali1, Harry C Ledebur4, Joseph M Rosen5, Hilton M Kaplan6, John A Wolf1,2, Douglas H Smith1,4, H Isaac Chen1,2, D Kacy Cullen1,2,3,4. 1. Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 2. Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania. 3. Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania. 4. Axonova Medical, Philadelphia, Pennsylvania. 5. Division of Plastic Surgery, Dartmouth-Hitchcock Medical Center, Dartmouth College, Lebanon, New Hampshire. 6. New Jersey Center for Biomaterials, Rutgers University, New Brunswick, New Jersey.
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).
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).
Authors: Alexandra Migga; Georg Schulz; Griffin Rodgers; Melissa Osterwalder; Christine Tanner; Holger Blank; Iwan Jerjen; Phil Salmon; William Twengström; Mario Scheel; Timm Weitkamp; Christian M Schlepütz; Jan S Bolten; Jörg Huwyler; Gerhard Hotz; Srinivas Madduri; Bert Müller Journal: J Med Imaging (Bellingham) Date: 2022-03-31
Authors: Rui D Alvites; Mariana V Branquinho; Ana C Sousa; Federica Zen; Monica Maurina; Stefania Raimondo; Carla Mendonça; Luís Atayde; Stefano Geuna; Artur S P Varejão; Ana C Maurício Journal: Int J Mol Sci Date: 2021-01-30 Impact factor: 5.923
Authors: Justin C Burrell; Suradip Das; Franco A Laimo; Kritika S Katiyar; Kevin D Browne; Robert B Shultz; Vishal J Tien; Phuong T Vu; Dmitriy Petrov; Zarina S Ali; Joseph M Rosen; D Kacy Cullen Journal: Bioact Mater Date: 2022-03-24
Authors: Dmitriy Petrov; Justin C Burrell; Kevin D Browne; Franco A Laimo; Sanford E Roberts; Zarina S Ali; D Kacy Cullen Journal: Front Surg Date: 2022-03-07