Advances and Future Applications of Augmented Peripheral Nerve Regeneration

Jones, Salazar; Eisenberg, Howard M.; Jia, Xiaofeng

doi:10.3390/ijms17091494

Cited by 86 publications

(61 citation statements)

References 134 publications

(189 reference statements)

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“…Autogenous materials, which include arteries, veins, muscle, tendon, and epineural sheath, are potentially efficacious as shown by some experimental use and small case studies; however, this class of nerve conduits has not yet demonstrated enough efficacy to make it to the clinic. 5,40,41 Allografts and xenografts are alternatives to autogenous nerve grafts, as they are readily accessible and unlimited in supply. However, transplantation of allografts usually requires immunosuppressive therapy, and the costs are considerably more expensive.…”

Section: Methodsmentioning

confidence: 99%

“…In addition to the various aforementioned strategies to augment the efficacy of nerve tubes, non-scaffold modifications such as growth factor supplementation and stem cell transplantation can also be incorporated into advanced scaffold technologies to further optimize peripheral nerve repair. 40,41 …”

Section: Synergy With Other Peripheral Nerve Regeneration Therapiesmentioning

confidence: 99%

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Biomimetic neural scaffolds: a crucial step towards optimal peripheral nerve regeneration

et al. 2018

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Peripheral nerve injury is a common disease that affects more than 20 million people in the United States alone and remains a major burden to society. The current gold standard treatment for critical-sized nerve defects is autologous nerve graft transplantation; however, this method is limited in many ways and does not always lead to satisfactory outcomes. The limitations of autografts have prompted investigations into artificial neural scaffolds as replacements, and some neural scaffold devices have progressed to widespread clinical use; scaffold technology overall has yet to be shown to be consistently on a par with or superior to autografts. Recent advances in biomimetic scaffold technologies have opened up many new and exciting opportunities, and novel improvements in material, fabrication technique, scaffold architecture, and lumen surface modifications that better reflect biological anatomy and physiology have independently been shown to benefit overall nerve regeneration. Furthermore, biomimetic features of neural scaffolds have also been shown to work synergistically with other nerve regeneration therapy strategies such as growth factor supplementation, stem cell transplantation, and cell surface glycoengineering. This review summarizes the current state of neural scaffolds, highlights major advances in biomimetic technologies, and discusses future opportunities in the field of peripheral nerve regeneration.

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Section: Methodsmentioning

confidence: 99%

Section: Synergy With Other Peripheral Nerve Regeneration Therapiesmentioning

confidence: 99%

Biomimetic neural scaffolds: a crucial step towards optimal peripheral nerve regeneration

et al. 2018

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“…In particular, critical-sized nerve gaps present challenges to peripheral nerve repair as they portend poorer recovery. Currently, autograft implantation is considered the standard clinical treatment, however, limited availability of donor tissue, donor site morbidity, and size mismatch between donor and recipient nerves limit the application of this technique [2,3]. Thus, better repair strategies for peripheral nerve gap injuries are of great interest.…”

Section: Introductionmentioning

confidence: 99%

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

et al. 2018

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Peripheral nerve injuries often lead to incomplete recovery and contribute to significant disability to approximately 360,000 people in the USA each year. Stem cell therapy holds significant promise for peripheral nerve regeneration, but maintenance of stem cell viability and differentiation potential in vivo are still major obstacles for translation. Using a made-in-house 96-well vertical electrical stimulation (ES) platform, we investigated the effects of different stimulating pulse frequency, duration and field direction on human neural crest stem cell (NCSC) differentiation. We observed dendritic morphology with enhanced neuronal differentiation for NCSCs cultured on cathodes subject to 20 Hz, 100μs pulse at a potential gradient of 200 mV/mm. We further evaluated the effect of a novel cell-based therapy featuring optimized pulsatile ES of NCSCs for in vivo transplantation following peripheral nerve regeneration. 15 mm critical-sized sciatic nerve injuries were generated with subsequent surgical repair in sixty athymic nude rats. Injured animals were randomly assigned into five groups (N = 12 per group): blank control, ES, NCSC, NCSC + ES, and autologous nerve graft. Optimized ES was applied immediately after surgical repair for 1 h in ES and NCSC + ES groups. Recovery was assessed by behavioral (CatWalk gait analysis), wet muscle-mass, histomorphometric, and immunohistochemical analyses at either 6 or 12 weeks after surgery (N = 6 per group). Gastrocnemius muscle wet mass measurements in ES + NCSC group were comparable to autologous nerve transplantation and significantly higher than other groups (p < 0.05). Quantitative histomorphometric analysis and catwalk gait analysis showed similar improvements by ES on NCSCs (p < 0.05). A higher number of viable NCSCs was shown via immunochemical analysis, with higher Schwann cell (SC) differentiation in the NCSC + ES group compared to the NCSC group (p < 0.05). Overall, ES on NCSC transplantation significantly enhanced nerve regeneration after injury and repair, and was comparable to autograft treatment. Thus, ES can be a potent alternative to biochemical and physical cues for modulating stem cell survival and differentiation. This novel cell-based intervention presents an effective and safe approach for improved outcomes after peripheral nerve repair.

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“…Peripheral nerve injury is a major burden to healthcare systems worldwide, affects 1.4 million patients, and costs over $150 billion dollars every year (Jia et al, 2014; Jiang et al, 2017; Jones et al, 2016; Taylor et al, 2008). Preclinical rodent studies are particularly valuable due to low cost and high translational potential (Kizilay et al, 2016; Wang et al, 2016), however, researchers must rely on postmortem pathological evaluation with only limited ways to evaluate functional recovery (Bervar, 2000; de Medinaceli et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

Establishing a reliable gait evaluation method for rodent studies

Chen

Zhang

et al. 2017

Journal of Neuroscience Methods

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BACKGROUND CatWalk is one of the most popular tools for evaluating gait recovery in preclinical research, however, there is currently no consensus on which of the many gait parameters captured by CatWalk can reliably model recovery. There are conflicting interpretations of results, along with many common but seldom reported problems such as heel walking and poor compliance. NEW METHOD We developed a systematic manual classification method that overcomes common problems such as heel walking and poor compliance. By correcting automation errors and removing inconsistent gait cycles, we isolated stretches of recordings that are more reliable for analysis. Recovery outcome was also assessed by quantitative histomorphometric analysis of myelinated axons. RESULTS While 40–60% of runs were erroneously classified without manual intervention, we corrected all errors with our new method, and showed that Stand Time, Duty Cycle, and Swing Speed are able to track significant differences over time and between experimental groups (all p<0.05). The usability of print area and intensity parameters requires further validation beyond the capabilities of CatWalk. COMPARISON WITH EXISTING METHOD(S) There is currently no strategy that addresses problems such as heel walking and poor compliance, and therefore no standard set of parameters that researchers can rely on to report their findings. CONCLUSION Manual classification is a crucial step to generate reliable CatWalk data, and Stand Time, Duty Cycle, and Swing Speed are suitable parameters for evaluating gait recovery. Static parameters such as print area and intensity should be used with extreme caution.

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Advances and Future Applications of Augmented Peripheral Nerve Regeneration

Cited by 86 publications

References 134 publications

Biomimetic neural scaffolds: a crucial step towards optimal peripheral nerve regeneration

Biomimetic neural scaffolds: a crucial step towards optimal peripheral nerve regeneration

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

Establishing a reliable gait evaluation method for rodent studies

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