Scientific Online Resource System

Biomedical Reviews

Designing an ideal 3D-bioprint conduit for axonal repair and regeneration: a neurosurgical perspective

Caleb Stewart, Chin Fung Kelvin Kan, Doan Nguyen, Olawale Sulaiman


Peripheral nerve injuries occur through three mechanisms, specifically, crush, compression or transection. Disruption of communication between the peripheral and central nervous system follows and leads to motor and sensory deficits. Peripheral nerves in humans have a limited capacity to self-regenerate following injury, which makes nerve transfer the current gold-standard for treatment. Functional nerve regeneration is contingent on several factors ranging from span of injury and the age of the patient. Bioprinted nerve guidance conduits are an emerging candidate for treating peripheral nerve injuries. To optimize the performance of nerve guidance conduits, a firm understanding of neurobiology and the pathophysiology following injury is necessary. This article provides an overview of nerve regeneration and the desirable features when designing a nerve conduit from a neurosurgical perspective.

Full Text


Daroff RB, Bradley WG. Bradley’s Neurology in Clinical Practice 6th ed. Elsevier/Saunders, 2012

Johnson BN, Jia X. 3D printed nerve guidance chan-nels: computer-aided control of geometry, physical cues, biological supplements and gradients. Neural Regen Res 2016; 11(10): 1568-1569. DOI: 10.4103/1673-5374.193230

Grinsell D,Keating CP. Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. Biomed Res Int 2014; 2014: 698256. DOI: 10.1155/2014/698256

Lundborg G. Richard P. Bunge memorial lecture. Nerve injury and repair - a challenge to the plastic brain. J Peripher Nerv Syst 2003; 8(4): 209-226. DOI: 10.1111/j.1085-9489.2003.03027.x.

Taylor CA, Braza D, Rice JB,Dillingham T. The incidence of peripheral nerve injury in extremity trauma. Am J Phys Med Rehabil 2008; 87(5): 381-385. DOI: 10.1097/PHM.0b013e31815e6370

Noble J, Munro CA, Prasad VS,Midha R. Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. J Trauma 1998; 45(1): 116-122. DOI: 10.1097/00005373-199807000-00025

Lee SK,Wolfe SW. Peripheral nerve injury and repair. J Am Acad Orthop Surg 2000; 8(4): 243-252. DOI: 10.5435/JAAOS-20-08-506.

Winn HR,Youmans JR. Youmans neurological surgery 5th edition. Saunders, 2004

Millesi H. Progress in peripheral nerve reconstruction. World J Surg 1990; 14(6): 733-747. DOI: 10.1007/bf01670520

Mackinnon SE. Microsurgical repair of peripheral nerves and nerve grafts. In: Mackinnon SE, C. H. Thorne SPB, R. W. Beasley, S. J. Aston, G. C. Gurtner, S. L. Spear, Ed. Grabb & Smith’s Plastic Surgery. Lippincott Williams & Wilkins, 2006; 561-589

Menorca RM, Fussell TS,Elfar JC. Nerve physiology: mechanisms of injury and recovery. Hand Clin 2013; 29(3): 317-330. DOI: 10.1016/j.hcl.2013.04.002

Spector JG, Lee P, Derby A,Roufa DG. Comparison of rabbit facial nerve regeneration in nerve growth factor-containing silicone tubes to that in autologous neural grafts. Ann Otol Rhinol Laryngol 1995; 104(11): 875-885. DOI: 10.1177/000348949510401110

Kornfeld T, Vogt PM,Radtke C. Nerve grafting for peripheral nerve injuries with extended defect sizes. Wien Med Wochenschr 2019; 169(9-10): 240-251. DOI: 10.1007/s10354-018-0675-6

Mandrycky C, Wang Z, Kim K,Kim DH. 3D bioprinting for engineering complex tissues. Biotechnol Adv 2016; 34(4): 422-434. DOI: 10.1016/j.biotechadv.2015.12.011

Laura Simionescu M. Traumatic mononeuropathies. 2019; Available from:

Chhabra A, Ahlawat S, Belzberg A,Andreseik G. Peripheral nerve injury grading simplified on MR neurography: As referenced to Seddon and Sunderland classifications. Indian J Radiol Imaging 2014; 24(3): 217-224. DOI: 10.4103/0971-3026.137025

Caillaud M, Richard L, Vallat JM, Desmouliere A,Billet

F. Peripheral nerve regeneration and intraneural revascularization. Neural Regen Res 2019; 14(1): 24-33. DOI: 10.4103/1673-5374.243699

Alvites R, Rita Caseiro A, Santos Pedrosa S, Vieira Branquinho M, Ronchi G, Geuna S, et al. Peripheral nerve injury and axonotmesis: State of the art and recent advances. Cogent Medicine 2018; 5(1). DOI: 10.1080/2331205X.2018.1466404

Pfister BJ, Gordon T, Loverde JR, Kochar AS, Mackinnon SE,Cullen DK. Biomedical engineering strategies for peripheral nerve repair: surgical applications, state of the art, and future challenges. Crit Rev Biomed Eng 2011; 39(2):

-124. DOI: 10.1615/CritRevBiomedEng.v39.i2.20

Sunderland S. A classification of peripheral nerve injuries producing loss of function. Brain 1951; 74(4): 491-516. DOI: 10.1093/brain/74.4.491

Seddon HJ. Three types of nerve injury. Brain 1943; 66(4): 237-288. DOI: 10.1093/brain/66.4.237

Kanamori A, Catrinescu MM, Belisle JM, Costantino S,Levin LA. Retrograde and Wallerian axonal degeneration occur synchronously after retinal ganglion cell ax-otomy. Am J Pathol 2012; 181(1): 62-73. DOI: 10.1016/j. ajpath.2012.03.030

Tezcan AH. Peripheral Nerve Injury and Current Treatment Strategies. In: Tezcan AH, Maurício AC. Peripheral Nerve Regeneration - From Surgery to New Therapeutic Approaches Including Biomaterials and Cell-Based Therapies Development. InTechOpen, 2017. DOI: 10.5772/intechopen.68345.

Kastriti ME,Adameyko I. Specification, plasticity and evolutionary origin of peripheral glial cells. Curr Opin Neurobiol 2017; 47: 196-202. DOI: 10.1016/j. conb.2017.11.004

Frostick SP, Yin Q, Kemp GJ. Schwann cells, neurotrophic factors, and peripheral nerve regeneration. Microsurgery 1998; 18(7): 397-405. DOI: 10.1002/(sici)1098-2752(1998)18:7<397::Aid-micr2>3.0.Co;2-f

Meirelles L, Caplan A, Nardi N. Pericytes as the Source of Mesenchymal Stem Cells. Resident Stem Cells and Regenerative Therapy 2013: 233-250. DOI: 10.1016/B978-0-12-416012-5.00012-8

Cattin AL, Burden JJ, Van Emmenis L, Mackenzie FE, Hoving JJ, Garcia Calavia N, et al. Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves. Cell 2015; 162(5): 1127-1139. DOI: 10.1016/j.cell.2015.07.021

Garcia-Diaz B, Bachelin C, Coulpier F, Gerschenfeld G, Deboux C, Zujovic V, et al. Blood vessels guide Schwann cell migration in the adult demyelinated CNS through Eph/ephrin signaling. Acta Neuropathol 2019; 138(3):

- 476. DOI: 10.1007/s00401-019-02011-1

Silver J. CNS regeneration: only on one condition. Curr Biol 2009; 19(11): R444-446. DOI: 10.1016/j. cub.2009.04.026

Gordon T, English AW. Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise. Eur J Neurosci 2016; 43(3): 336-350. DOI: 10.1111/ejn.13005

Gilbert SF. Developmental Biology 6th ed. Sunderland, 2000.

Bashaw GJ, Klein R. Signaling from axon guidance receptors. Cold Spring Harb Perspect Biol 2010; 2(5): a001941. DOI: 10.1101/cshperspect.a001941

Tuttle R, O’Leary DD. Neurotrophins rapidly modulate growth cone response to the axon guidance molecule, collapsin-1. Mol Cell Neurosci 1998; 11(1-2): 1-8. DOI: 10.1006/mcne.1998.0671

Seeds NW, Siconolfi LB, Haffke SP. Neuronal extracellular proteases facilitate cell migration, axonal growth, and pathfinding. Cell Tissue Res 1997; 290(2): 367-370. DOI: 10.1007/s004410050942

Elisa V. Cell-Cell and Cell-Matrix Interactions during Axons Guidance. In: Elisa V, Abreu GEA. Neurons-Dendrites and Axons, InTechOpen, 2018; DOI: 10.5772/intechopen.73741

Safieh-Garabedian B, Poole S, Allchorne A, Winter J, Woolf CJ. Contribution of interleukin-1 beta to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia. Br J Pharmacol 1995; 115(7): 1265-1275. DOI: 10.1111/j.1476-5381.1995.tb15035.x

Oliveira KMC, Pindur L, Han Z, Bhavsar MB, Barker JH, Leppik L. Time course of traumatic neuroma development. PLoS One 2018; 13(7): e0200548. DOI: 10.1371/journal.pone.0200548

Lunn ER, Brown MC, Perry VH. The pattern of axonal degeneration in the peripheral nervous system varies with different types of lesion. Neuroscience 1990; 35(1):

- 165. DOI: 10.1016/0306-4522(90)90130-v

Sulaiman W, Gordon T. Neurobiology of peripheral nerve injury, regeneration, and functional recovery: from bench top research to bedside application. Ochsner J 2013; 13(1): 100-108.

Chaldakov GN, Fiore M, Stankulov IS, Manni L, Hristova MG, Antonelli A, et al. Neurotrophin presence in human coronary atherosclerosis and metabolic syndrome: a role for NGF and BDNF in cardiovascular disease? Prog Brain Res 2004; 146: 279-289. DOI: 10.1016/S0079-6123(03)46018-4

Sulaiman W, Dreesen TD. Effect of local application of transforming growth factor-beta at the nerve repair site following chronic axotomy and denervation on the expression of regeneration-associated genes. Laboratory investigation. J Neurosurg 2014; 121(4): 859-874. DOI: 10.3171/2014.4.JNS131251

Millesi H. The nerve gap. Theory and clinical practice. Hand Clin 1986; 2(4): 651-663.

Barton MJ, Morley JW, Stoodley MA, Lauto A, Mahns DA. Nerve repair: toward a sutureless approach. Neurosurg Rev 2014; 37(4): 585-595. DOI: 10.1007/s10143-014-0559-1

Menovsky T, Beek JF. Laser, fibrin glue, or suture repair of peripheral nerves: a comparative functional, histological, and morphometric study in the rat sciatic nerve. J Neurosurg 2001; 95(4): 694-699. DOI: 10.3171/jns.2001.95.4.0694

Millesi H. Healing of nerves. Clin Plast Surg 1977; 4(3):


Gordon T. Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans. Neurotherapeutics 2016; 13(2): 295-310. DOI: 10.1007/s13311-015-0415-1

Seta H, Maki D, Kazuno A, Yamato I, Nakajima N, Soeda S, et al. Voluntary Exercise Positively Affects the Recovery of Long-Nerve Gap Injury Following Tube-Bridging with Human Skeletal Muscle-Derived Stem Cell Transplantation. J Clin Med 2018; 7(4). DOI: 10.3390/jcm7040067

Armada-da-Silva PA, Pereira C, Amado S, Veloso AP. Role of physical exercise for improving posttraumatic nerve regeneration. Int Rev Neurobiol 2013; 109: 125-

DOI: 10.1016/B978-0-12-420045-6.00006-7

Ray WZ, Mackinnon SE. Management of nerve gaps: autografts, allografts, nerve transfers, and end-to-side neurorrhaphy. Exp Neurol 2010; 223(1): 77-85. DOI: 10.1016/j.expneurol.2009.03.031

Liao WC, Chen JR, Wang YJ, Tseng GF. The efficacy of end-to-end and end-to-side nerve repair (neurorrhaphy) in the rat brachial plexus. J Anat 2009; 215(5): 506-521. DOI: 10.1111/j.1469-7580.2009.01135.x

Mackinnon SE. New directions in peripheral nerve surgery. Ann Plast Surg 1989; 22(3): 257-273. DOI: 10.1097/00000637-198903000-00013

Faroni A, Mobasseri SA, Kingham PJ, Reid AJ. Peripheral nerve regeneration: experimental strategies and future perspectives. Adv Drug Deliv Rev 2015; 82-83: 160-167. DOI: 10.1016/j.addr.2014.11.010

Evans GR. Peripheral nerve injury: a review and approach to tissue engineered constructs. Anat Rec 2001; 263(4):

- 404. DOI: 10.1002/ar.1120

Mackinnon SE. Results of nerve repair and grafting. In: Mackinnon SE, Midha Z. Surgery of Peripheral Nerves. Thieme, 1988; 123–124

Arslantunali D, Dursun T, Yucel D, Hasirci N, Hasirci

V. Peripheral nerve conduits: technology update. Med Devices (Auckl) 2014; 7: 405-424. DOI: 10.2147/MDER. S59124

Sabongi RG, Fernandes M, Dos Santos JB. Peripheral nerve regeneration with conduits: use of vein tubes. Neural Regen Res 2015; 10(4): 529-533.DOI: 10.4103/1673-5374.155428

Midha R, Nag S, Munro CA, Ang LC. Differential response of sensory and motor axons in nerve allografts after withdrawal of immunosuppressive therapy. J Neurosurg 2001; 94(1): 102-110. DOI: 10.3171/jns.2001.94.1.0102

Mackinnon SE, Hudson AR, Falk RE, Kline D, Hunter

D. Peripheral nerve allograft: an immunological assess-ment of pretreatment methods. Neurosurgery 1984; 14(2): 167-171. DOI: 10.1227/00006123-198402000-00008

Gu X, Ding F, Yang Y, Liu J. Construction of tissue engineered nerve grafts and their application in peripheral nerve regeneration. Prog Neurobiol 2011; 93(2): 204-230. DOI: 10.1016/j.pneurobio.2010.11.002

Yanev S, Aloe L, Fiore M, Chaldakov GN. Neurotrophic and metabotrophic potential of nerve growth factor and brain-derived neurotrophic factor: Linking cardiometa-bolic and neuropsychiatric diseases. World J Pharmacol 2013; 2(4): 92-99. DOI: 10.5497/wjp.v2.i4.92

Allen SJ, Watson JJ, Shoemark DK, Barua NU,Patel NK. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther 2013; 138(2): 155-

DOI: 10.1016/j.pharmthera.2013.01.004

Alsina FC, Ledda F, Paratcha G. New insights into the control of neurotrophic growth factor receptor signaling: implications for nervous system development and repair. J Neurochem 2012; 123(5): 652-661. DOI: 10.1111/jnc.12021

Allodi I, Udina E, Navarro X. Specificity of peripheral nerve regeneration: interactions at the axon level. Prog Neurobiol 2012; 98(1): 16-37. DOI: 10.1016/j.pneuro-bio.2012.05.005

Daly W, Yao L, Zeugolis D, Windebank A, Pandit A. A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery. J R Soc Interface 2012; 9(67): 202-221. DOI: 10.1098/rsif.2011.0438

Marquardt LM, Sakiyama-Elbert SE. Engineering peripheral nerve repair. Curr Opin Biotechnol 2013; 24(5): 887-892. DOI: 10.1016/j.copbio.2013.05.006

Mohanna PN, Young RC, Wiberg M, Terenghi G. A com-posite poly-hydroxybutyrate-glial growth factor conduit for long nerve gap repairs. J Anat 2003; 203(6): 553-565. DOI: 10.1046/j.1469-7580.2003.00243.x

Navarro X, Vivo M, Valero-Cabre A. Neural plasticity after peripheral nerve injury and regeneration. Prog Neurobiol 2007; 82(4): 163-201. DOI: 10.1016/j.pneurobio.2007.06.005

Midha R, Munro CA, Dalton PD, Tator CH, Shoichet MS. Growth factor enhancement of peripheral nerve regenera-tion through a novel synthetic hydrogel tube. J Neurosurg 2003; 99(3): 555-565. DOI: 10.3171/jns.2003.99.3.0555

Levi-Montalcini R. The nerve growth factor 35 years later. Science 1987; 237(4819): 1154-1162. DOI: 10.1126/science.3306916

Alsina FC, Ledda F, Paratcha G. New insights into the control of neurotrophic growth factor receptor signaling: Implications for nervous system development and repair. Journal of Neurochemistry 2012; 123(5): 652-661. DOI:10.1111/jnc.12021

Hadlock T, Sundback C, Koka R, Hunter D, Cheney M, Vacanti J. A novel, Biodegradable polymer conduit delivers neurotrophins and promotes nerve regeneration. Laryngoscope 1999; 109(9): 1412-1416. DOI: 10.1097/00005537-199909000-00010

Thanos PK, Okajima S, Terzis JK. Ultrastructure and cellular biology of nerve regeneration. J Reconstr Microsurg 1998; 14(6): 423-436. DOI: 10.1055/s-2007-1000203

McKay R. Stem cells in the central nervous system. Science 1997; 276(5309): 66-71. DOI: 10.1126/sci-ence.276.5309.66

Ren Z, Wang Y, Peng J, Zhao Q, Lu S. Role of stem cells in the regeneration and repair of peripheral nerves. Rev Neurosci 2012; 23(2): 135-143. DOI: 10.1515/revneuro-2011-0069

Koshizuka S, Okada S, Okawa A, Koda M, Murasawa M, Hashimoto M, et al. Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice. J Neuropathol Exp Neurol 2004; 63(1):64-72. DOI: 10.1093/jnen/63.1.64

Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA 2008; 105(15): 5856-5861. DOI: 10.1073/pnas.0801677105

Tung TH, Mackinnon SE. Nerve transfers: indications, techniques, and outcomes. J Hand Surg Am 2010; 35(2):332-341. DOI: 10.1016/j.jhsa.2009.12.002

Blakemore WF. The case for a central nervous system (CNS) origin for the Schwann cells that remyelinate CNS axons following concurrent loss of oligodendrocytes and astrocytes. Neuropathol Appl Neurobiol 2005; 31(1):1-10. DOI: 10.1111/j.1365-2990.2005.00637.x

Zhang Q, Nguyen P, Xu Q, Park W, Lee S, Furuhashi A, et al. Neural Progenitor-Like Cells Induced from Human Gingiva-Derived Mesenchymal Stem Cells Regulate Myelination of Schwann Cells in Rat Sciatic Nerve Regeneration. Stem Cells Transl Med 2017; 6(2): 458-470. DOI: 10.5966/sctm.2016-0177

Xu L, Zhou S, Feng GY, Zhang LP, Zhao DM, Sun Y, et al. Neural stem cells enhance nerve regeneration after sciatic nerve injury in rats. Mol Neurobiol 2012; 46(2):265-274. 10. DOI: 1007/s12035-012-8292-7

Chen Z-L, Yu W-M, Strickland S. Peripheral Regenera-tion. Annual Review of Neuroscience 2007; 30(1): 209-

DOI: 10.1146/annurev.neuro.30.051606.094337

Llado J, Haenggeli C, Maragakis NJ, Snyder EY, Roth-stein JD. Neural stem cells protect against glutamate-induced excitotoxicity and promote survival of injured motor neurons through the secretion of neurotrophic factors. Mol Cell Neurosci 2004; 27(3): 322-331. DOI: 10.1016/j.mcn.2004.07.010

Bressan RB, Dewari PS, Kalantzaki M, Gangoso E, Matju-saitis M, Garcia-Diaz C, et al. Efficient CRISPR/Cas9-assisted gene targeting enables rapid and precise genetic manipulation of mammalian neural stem cells. Development 2017; 144(4): 635-648. DOI: 10.1242/dev.140855

Pabari A, Yang SY, Mosahebi A, Seifalian AM. Recent advances in artificial nerve conduit design: strategies for the delivery of luminal fillers. J Control Release 2011; 156(1): 2-10. DOI: 10.1016/j.jconrel.2011.07.001

Sarker MD, Naghieh S, McInnes AD, Schreyer DJ, Chen X. Regeneration of peripheral nerves by nerve guidance conduits: Influence of design, biopolymers, cells, growth factors, and physical stimuli. Prog Neurobiol 2018; 171:125-150. DOI: 10.1016/j.pneurobio.2018.07.002

Tonchev A, Aloe L, Bełtowski J, Rancic G, Bojanic V, Atanassova P, et al. Adipose-derived stem cells as a remedy. Adipobiology 2010; 2: 51. DOI: 10.14748/adipo. v2.260

Zhang R, Rosen JM. The role of undifferentiated adipose-derived stem cells in peripheral nerve repair. Neural Regen Res 2018; 13(5): 757-763. DOI: 10.4103/1673-5374.232457

Abbas O, Borman H, Uysal Ç, Gonen Z, Aydin L, Helvacıoglu F, et al. Adipose-derived stem cells enhance axonal regeneration through cross-facial nerve grafting in a rat model of facial paralysis. Plastic Reconstr Surg 2016; 138: 387-396. DOI: 10.1097/PRS.0000000000002351

Bloanca V, Ceausu AR, Jitariu AA, Barmayoun A, Mos R, Crainiceanu Z, et al. Adipose tissue graft improves early but not late stages of nerve regeneration. In Vivo 2017; 31(4): 649-655. DOI: 10.21873/invivo.11107

Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Quinn G, et al. Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology 2007; 46(1): 219-228. DOI: 10.1002/hep.21704

Chiono V, Tonda-Turo C. Trends in the design of nerve guidance channels in peripheral nerve tissue engineering. Prog Neurobiol 2015; 131: 87-104. DOI: 10.1016/j. pneurobio.2015.06.001

Freier T, Montenegro R, Shan Koh H, Shoichet MS. Chitin-based tubes for tissue engineering in the nervous system. Biomaterials 2005; 26(22): 4624-4632. DOI: 10.1016/j.biomaterials.2004.11.040

Chiono V, Ciardelli G, Vozzi G, Sotgiu MG, Vinci B, Domenici C, et al. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ϵ-caprolactone) blends for tissue engineering applications in the form of hollow fibers. J Biomed Mater Res. 2008; 85A(4): 938-953. DOI: 10.1002/jbm.a.31513

Al-Majed AA, Brushart TM, Gordon T. Electrical stimu-lation accelerates and increases expression of BDNF and trkB mRNA in regenerating rat femoral motoneu-rons. Eur J Neurosci 2000; 12(12): 4381-4390. DOI: 10.1111/j.1460-9568.2000.01341.x.

Xu H, Holzwarth JM, Yan Y, Xu P, Zheng H, Yin Y, et al. Conductive PPY/PDLLA conduit for peripheral nerve regeneration. Biomaterials 2014; 35(1): 225-235. 10.1016/j.biomaterials.2013.10.002

Belkas JS, Shoichet MS, Midha R. Peripheral nerve regeneration through guidance tubes. Neurologic Res 2004; 26(2): 151-160. DOI: 10.1179/016164104225013798

Ribeiro-Resende VT, Koenig B, Nichterwitz S, Ober-hoffner S, Schlosshauer B. Strategies for inducing the formation of bands of Bungner in peripheral nerve re-generation. Biomaterials 2009; 30(29): 5251-5259. DOI: 10.1016/j.biomaterials.2009.07.007

Brushart TM, Mathur V, Sood R, Koschorke GM. Joseph H. Boyes Award. Dispersion of regenerating axons across enclosed neural gaps. J Hand Surg Am 1995; 20(4): 557-564. DOI: 10.1016/s0363-5023(05)80267-9

Chang CJ, Hsu SH. The effect of high outflow permeability in asymmetric poly(dl-lactic acid-co-glycolic acid) conduits for peripheral nerve regeneration. Biomaterials 2006; 27(7): 1035-1042. DOI: 10.1016/j.biomaterials.2005.07.003

Groves ML, McKeon R, Werner E, Nagarsheth M, Meador W, English AW. Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation. Exp Neuro 2005; (2): 278-292. DOI: 10.1016/j.expneurol.2005.04.007.

Cangellaris O, Gillette M. Biomaterials for enhancing neuronal repair. Front Mater 2018; 5: 21. DOI: 10.3389/fmats.2018.00021

Torday JS. A central theory of biology. Med Hypotheses 2015; 85(1): 49-57. DOI: 10.1016/j.mehy.2015.03.019

Zochodne DW, Ho LT. Hyperemia of injured peripheral nerve: sensitivity to CGRP antagonism. Brain Res 1992; 598(1-2): 59-66. DOI: 10.1016/0006-8993(92)90168-9

Zochodne DW, Ho LT. Endoneurial microenvironment and acute nerve crush injury in the rat sciatic nerve. Brain Res 1990; 535(1): 43-48. DOI: 10.1016/0006-8993(90)91822-x

Bearden SE, Segal SS. Microvessels promote motor nerve survival and regeneration through local VEGF release following ectopic reattachment. Microcirculation 2004; 11(8): 633-644. DOI: 10.1080/10739680490517659.

Xu QG, Zochodne DW. Ischemia and failed regeneration in chronic experimental neuromas. Brain Res 2002; 946(1): 24-30. DOI: 10.1016/s0006-8993(02)02820-2

Risau W. Mechanisms of angiogenesis. Nature 1997; 386(6626): 671-674. DOI: 10.1038/386671a0

Kubis N, Levy BI. Vasculogenesis and angiogenesis: molecular and cellular controls. Part 1: growth fac-tors. Interv Neuroradiol 2003; 9(3): 227-237. DOI: 10.1177/159101990300900301

Carmeliet P, Tessier-Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature 2005; 436(7048):193- 200. DOI: 10.1038/nature03875

Serini G, Maione F, Giraudo E, Bussolino F. Semaphorins and tumor angiogenesis. Angiogenesis 2009; 12(2): 187-193. DOI: 10.1007/s10456-009-9138-4

Kaizawa Y, Kakinoki R, Ikeguchi R, Ohta S, Noguchi T, Takeuchi H, et al. A Nerve Conduit Containing a Vascular Bundle and Implanted With Bone Marrow Stromal Cells and Decellularized Allogenic Nerve Matrix. Cell Transplant 2017; 26(2): 215-228. DOI: 10.3727/096368916X692951

Al-Majed AA, Tam SL,Gordon T. Electrical stimulation accelerates and enhances expression of regeneration-associated genes in regenerating rat femoral motoneurons. Cell Mol Neurobiol 2004; 24(3):379-402. DOI:10.1023/B:CEMN.0000022770.66463.f7.

Gordon T, Udina E, Verge VM, de Chaves EI. Brief electrical stimulation accelerates axon regeneration in the peripheral nervous system and promotes sensory axon regeneration in the central nervous system. Motor Control 2009; 13(4): 412-441. DOI:10.1123/mcj.13.4.412.

Lin YC, Kao CH, Chen CC, Ke CJ, Yao CH, Chen YS. Time-course effect of electrical stimulation on nerve regeneration of diabetic rats. PLoS One 2015; 10(2): e0116711. DOI:10.1371/journal.pone.0116711



Article Tools
Email this article (Login required)
About The Authors

Caleb Stewart
The University of Queensland-Ochsner Clinical School, Herston, Australia

Faculty of Medicine

Chin Fung Kelvin Kan
The University of Queensland-Ochsner Clinical School, Herston, Australia

Faculty of Medicine

Doan Nguyen
Laboratory of Translational Neurosurgery Research, Ochsner Clinic Foundation, New Orleans, LA
United States

Olawale Sulaiman
Department of Neurological Surgery, Ochsner Clinic Foundation, New Orleans, LA
United States

Font Size