3D Printed Anatomical Nerve Regeneration Pathways

Johnson, Blake N.; Lancaster, Karen Z.; Zhen, Gehua; He, Jialong; Gupta, Maneesh K.; Kong, Yong Lin; Engel, Esteban A.; Krick, Kellin; Ju, Alex; Meng, Fanben; Enquist, Lynn W.; Jia, Xiaofeng; McAlpine, Michael C.

doi:10.1002/adfm.201501760

Cited by 250 publications

(260 citation statements)

References 71 publications

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“…Using 3D printing technology, Johnson et al developed bifurcation nerve scaffolds with imbedded growth factor gradients for the first time, and demonstrated its therapeutic effect in a rat nerve regeneration model. 129 Our approach loaded path specific neurotrophic factors (NGF for axons and GDNF for Schwann cells) to promote selective regeneration of peripheral nerves, and in vivo results demonstrated that functional recovery was improved with these novel devices. 129 Yurie et al further confirmed in rats that 3D printed conduits promoted nerve regeneration.…”

Section: Fabricationmentioning

confidence: 92%

“…129 Our approach loaded path specific neurotrophic factors (NGF for axons and GDNF for Schwann cells) to promote selective regeneration of peripheral nerves, and in vivo results demonstrated that functional recovery was improved with these novel devices. 129 Yurie et al further confirmed in rats that 3D printed conduits promoted nerve regeneration. 130 Many reports have shown that 3D printing technology provides an exciting new fabrication technique that may be able to fulfill clinical needs for complicated and patient-specific artificial nerve grafts which cannot be satisfied by conventional fabrication techniques.…”

Section: Fabricationmentioning

confidence: 92%

“…For example, specific growth factors can be integrated into various locations of 3D printed neural scaffolds for bifurcating nerve gaps, allowing for possibly better innervation specificity of the motor and sensory neurons. 129 Growth factors can also be encased in physical lumen fillings using hydrogel-forming collagen, alginate, heparin, and heparin sulfate, which can sustain the efficacy and prevent degradation of growth factors.…”

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: Fabricationmentioning

confidence: 92%

Section: Fabricationmentioning

confidence: 92%

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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“…We have described the methodology of CatWalk (Noldus Information Technology, The Netherlands) before [6,37,38]. Briefly, one week prior to surgery, animals were trained daily on a CatWalk runway until they were able to make consecutive uninterrupted runs.…”

Section: Methodsmentioning

confidence: 99%

“…Various strategies for improving nerve repair have been proposed in basic, pre-clinical and clinical trials [4–6]. Stem cell transplantation therapy has emerged as a particularly promising strategy to improve outcomes in pre-clinical models [7–9].…”

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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3D Printed Anatomical Nerve Regeneration Pathways

Cited by 250 publications

References 71 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

Some Significant Examples

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