To reverse or not to reverse? A systematic review of autograft polarity on functional outcomes following peripheral nerve repair surgery

Roberts, Sanford E.; Thibaudeau, Stéphanie; Burrell, Justin C.; Zager, Eric L.; Cullen, D. Kacy; Levin, L. Scott

doi:10.1002/micr.30133

Cited by 27 publications

(25 citation statements)

References 26 publications

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“…For autograft repairs, a reverse-autograft technique was used. 37 For NGT, NGT+DRG, and TENG repairs, the nerve stumps were carefully inserted into each end of the nerve guidance tube with an overlap of 1 mm, and the epineurium was secured to the tube using 8-0 non-absorbable prolene sutures. The NGT+DRG repair contained DRG neurons embedded in collagen and NGT repairs contained collagen only as described above.…”

Section: Surgical Proceduresmentioning

confidence: 99%

Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair

Maggiore

Burrell

Browne

et al. 2019

Preprint

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Peripheral nerve injury (PNI) impacts millions annually, often leaving debilitated patients with minimal repair options to improve functional recovery. Our group has previously developed tissue engineered nerve grafts (TENGs) featuring long, aligned axonal tracts from dorsal root ganglia (DRG) neurons that are fabricated in custom bioreactors using the process of axon "stretch-growth". We have shown that TENGs effectively serve as "living scaffolds" to promote regeneration across segmental nerve defects by exploiting the newfound mechanism of axonfacilitated axon regeneration, or "AFAR", by simultaneously providing haptic and neurotrophic support. To extend this work, the current study investigated the efficacy of living versus non-living regenerative scaffolds in preserving host sensory and motor neuron cell health, using retrograde dye transport as a proxy, following bridging of segmental nerve defects. Rats were assigned across five groups: naïve or repair using autograft, nerve guidance tube (NGT) with collagen, NGT + non-aligned DRG populations in collagen, or TENGs. We found that TENG repairs yielded equivalent regenerative capacity as autograft repairs based on preserved health of host spinal cord motor neurons and acute axonal regeneration, whereas NGT repairs or DRG neurons within an NGT exhibited reduced motor neuron preservation and diminished regenerative capacity.These acute regenerative benefits ultimately resulted in enhanced levels of functional recovery in animals receiving TENGs, at levels matching those attained by autografts. Our findings indicate that when used to bridge segmental nerve defects, TENGs preserve host spinal cord motor neuron health and regenerative capacity without sacrificing an otherwise uninjured nerve (as in the case of the autograft), and therefore represent a promising alternative strategy for neurosurgical repair following PNI.2 HIGHLIGHTS

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Section: Surgical Proceduresmentioning

confidence: 99%

Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair

Maggiore

Burrell

Browne

et al. 2019

Preprint

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“…ere were no significant differences in the CMAP, nerve conduction velocity, or total axon count between the orthodromic and antidromic nerve graft groups in this study. Of the six studies included in a systematic review of the effect of autograft polarity on functional outcomes following nerve graft [4], four [5][6][7]25] reported no difference and two [8,20] significant differences between a normally oriented and a reversed graft. In 1988, Ansselin and Davey used a rodent sciatic nerve model to examine axonal regeneration following peripheral nerve graft according to graft polarity [20].…”

Section: Discussionmentioning

confidence: 99%

“…According to anecdotal reports, many surgeons reverse the polarity of the autograft during autogenous nerve grafting, with the intent of improving nerve regeneration by mitigating the potential misrouting effects of arborization [4]. However, the optimal orientation of an autogenous nerve graft remains controversial.…”

Section: Introductionmentioning

confidence: 99%

“…is was disputed by Millesi, who found that nerve graft reversal did not enhance regeneration [9]. In a systematic review of the effect of autograft polarity on functional outcomes following peripheral nerve repair surgery, it was concluded that there were insufficient data suggesting that the polarity of an autologous nerve graft impacts on nerve regeneration and functional outcome [4]. Furthermore, only six studies were included in that review, and most of them were conducted more than 20 years ago.…”

Section: Introductionmentioning

confidence: 99%

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Nerve Repair and Orthodromic and Antidromic Nerve Grafts: An Experimental Comparative Study in Rabbit

Kim

Choi

Kim

et al. 2020

BioMed Research International

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Purpose. Although many surgeons have anecdotally described reversing the polarity of the autograft with the intent of improving regeneration, the optimal orientation of the autogenous nerve graft remains controversial. The aim of this study was to compare (1) the outcomes of orthodromic and antidromic nerve grafts to clarify the effect of nerve graft polarity and (2) the outcome of either form of nerve grafts with that of nerve repair. Methods. In 14 of the 26 rabbits used in this study, a 1 cm defect was made in the tibial nerve. An orthodromic nerve graft on one side and an antidromic nerve graft on the other were performed using a 1.2 cm long segment of the peroneal nerve. In the remaining 12 rabbits, the tibial nerve was transected completely and then repaired microscopically on one side but left untreated on the other. Electrophysiologic studies were performed in all animals at 8 weeks after surgery, and the sciatic nerves were harvested. Results. Compound motor action potential was visible in all rabbits treated by nerve repair but in only half of the rabbits treated by nerve graft. There was no significant difference in the compound motor action potential, nerve conduction velocity, or total number of axons between the orthodromic and antidromic nerve graft groups. However, in both groups, the outcome was significantly poorer than that of the nerve repair group. Conclusion. There was no significant difference by electromyographic or histologic evaluation between orthodromic and antidromic nerve grafts. Direct nerve repair with moderate tension may be a more effective treatment than nerve grafting.

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“…the proximal DPN stump sutured to the distal end of the sural nerve segment, and the distal DPN stump sutured to proximal end of the sural nerve segment) to minimize branching. 19 Also, in considering nerve and species selection for other applications, human-like fascicular organization is an important consideration for evaluation of peripheral nerve electrical interface devices, suggesting the benefits of a standardized large animal model with polyfascicular nerve architecture in this increasingly common application as well. 55 Clinically, the CPN is the most commonly injured peripheral nerve in the lower limb, 56 injuries will have a noticeable "hoof drop" that can be measured.…”

Section: Discussionmentioning

confidence: 99%

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

Burrell

Browne

Dutton

et al. 2019

Preprint

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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.

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To reverse or not to reverse? A systematic review of autograft polarity on functional outcomes following peripheral nerve repair surgery

Abstract: There is insufficient data to suggest that nerve autograft polarity has an impact on nerve regeneration and functional outcomes.

Cited by 27 publications

References 26 publications

Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair

Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair

Nerve Repair and Orthodromic and Antidromic Nerve Grafts: An Experimental Comparative Study in Rabbit

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

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