J Reconstr Microsurg 2023; 39(05): 392-404
DOI: 10.1055/s-0042-1758182
Original Article

Assessment of Human Epineural Conduit of Different Size Diameters on Efficacy of Nerve Regeneration and Functional Outcomes

Marcin Michal Strojny
1   Department of Orthopaedics, University of Illinois at Chicago, Chicago, Illinois, United States
2   Department of Surgery, Poznan University of Medical Sciences, Poznan, Poland
1   Department of Orthopaedics, University of Illinois at Chicago, Chicago, Illinois, United States
2   Department of Surgery, Poznan University of Medical Sciences, Poznan, Poland
1   Department of Orthopaedics, University of Illinois at Chicago, Chicago, Illinois, United States
1   Department of Orthopaedics, University of Illinois at Chicago, Chicago, Illinois, United States
2   Department of Surgery, Poznan University of Medical Sciences, Poznan, Poland
1   Department of Orthopaedics, University of Illinois at Chicago, Chicago, Illinois, United States
2   Department of Surgery, Poznan University of Medical Sciences, Poznan, Poland
› Author Affiliations
Funding This study was supported by the Musculoskeletal Transplant Foundation (MTF, NJ) grant #2014-06351.


Background Different types of nerve conduits are used to bridge peripheral nerve gaps when a tension-free repair is unattainable. To best support nerve regeneration, naturally occurring conduits have been tested. Since allografts offer an unlimited source of epineurium, we have developed human epineural conduit (hEC) as a novel technology to bridge nerve gaps. Considering acellular properties, and lack of immunogenic response, epineurium-derived conduits represent an attractive material, when compared with nerve allografts that require systemic immunosuppression. In this study, we introduce the hEC as a novel naturally occurring material applied for repair of nerve gaps after trauma.

Methods We tested the application of hEC created from human sciatic nerve in the restoration of 20 mm sciatic nerve defects in the nude rat model. Four experimental groups were studied: group 1: no repair control (n = 6), group 2: autograft control (n = 6), group 3: matched diameter hEC (n = 6), and group 4: large diameter hEC (n = 6). Functional tests of toe-spread and pin prick were performed at 1, 3, 6, 9, 12 weeks after repair. At 12 weeks, nerve samples were collected for immunostaining of Laminin B, S-100, glial fibrillary acidic protein (GFAP), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), von Willebrand factor, and histomorphometric analysis of myelin thickness, axonal density, fiber diameter, and percentage of the myelinated nerve fibers. Muscle samples were gathered for gastrocnemius muscle index (GMI) and muscle fiber area ratio measurements.

Results Best functional recovery, as well as GMI, was revealed for the autograft group, and was comparable to the matched hEC group. Significant differences were revealed between matched and large hEC groups in expression of S100 (p = 0.0423), NGF (p = 0.269), VEGF (p = 0.0003) as well as in percentage of myelinated fibers (p < 0.001) and axonal density (p = 0.0003).

Conclusion We established the feasibility of hEC creation. The innovative method introduces an alternative technique to autograft repair of nerve defects.

Authors' Contributions

M.M.S. performed experiments, collected, analyzed data, and wrote the manuscript. K.K. analyzed data and wrote the manuscript. S.B. analyzed data, performed statistical analysis, prepared figures, and edited manuscript. K.R. performed graphs, figures and edited manuscript. M.S. designed and supervised the project, and reviewed the article. All authors edited and approved the manuscript.

Publication History

Received: 07 June 2022

Accepted: 17 September 2022

Article published online:
15 November 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 IJpma FF, Van De Graaf RC, Meek MF. The early history of tubulation in nerve repair. J Hand Surg Eur Vol 2008; 33 (05) 581-586
  • 2 Kehoe S, Zhang XF, Boyd D. FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury 2012; 43 (05) 553-572
  • 3 Ray WZ, Mackinnon SE. Management of nerve gaps: autografts, allografts, nerve transfers, and end-to-side neurorrhaphy. Exp Neurol 2010; 223 (01) 77-85
  • 4 Siemionow M, Duggan W, Brzezicki G. et al. Peripheral nerve defect repair with epineural tubes supported with bone marrow stromal cells: a preliminary report. Ann Plast Surg 2011; 67 (01) 73-84
  • 5 Siemionow M, Cwykiel J, Uygur S. et al. Application of epineural sheath conduit for restoration of 6-cm long nerve defects in a sheep median nerve model. Microsurgery 2019; 39 (04) 332-339
  • 6 Siemionow M, Demir Y, Mukherjee AL. Repair of peripheral nerve defects with epineural sheath grafts. Ann Plast Surg 2010; 65 (06) 546-554
  • 7 Siemionow M, Strojny MM, Kozlowska K, Brodowska S, Grau-Kazmierczak W, Cwykiel J. Application of human epineural conduit supported with human mesenchymal stem cells as a novel therapy for enhancement of nerve gap regeneration. Stem Cell Rev Rep 2022; 18 (02) 642-659
  • 8 Yavuzer R, Ayhan S, Latifoğlu O, Atabay K. Turnover epineural sheath tube in primary repair of peripheral nerves. Ann Plast Surg 2002; 48 (04) 392-400
  • 9 Tetik C, Ozer K, Ayhan S, Siemionow K, Browne E, Siemionow M. Conventional versus epineural sleeve neurorrhaphy technique: functional and histomorphometric analysis. Ann Plast Surg 2002; 49 (04) 397-403
  • 10 Lubiatowski P, Unsal FM, Nair D, Ozer K, Siemionow M. The epineural sleeve technique for nerve graft reconstruction enhances nerve recovery. Microsurgery 2008; 28 (03) 160-167
  • 11 Siemionow M, Bobkiewicz A, Cwykiel J, Uygur S, Francuzik W. Epineural sheath jacket as a new surgical technique for neuroma prevention in the rat sciatic nerve model. Ann Plast Surg 2017; 79 (04) 377-384
  • 12 Siemionow M, Uygur S, Madajka M. Application of epineural sheath as a novel approach for fat volume maintenance. Ann Plast Surg 2017; 79 (06) 606-612
  • 13 Terzis J, Faibisoff B, Williams B. The nerve gap: suture under tension vs. graft. Plast Reconstr Surg 1975; 56 (02) 166-170
  • 14 Driscoll PJ, Glasby MA, Lawson GM. An in vivo study of peripheral nerves in continuity: biomechanical and physiological responses to elongation. J Orthop Res 2002; 20 (02) 370-375
  • 15 Wolfe EM, Mathis SA, Ovadia SA, Panthaki ZJ. Comparison of collagen and human amniotic membrane nerve wraps and conduits for peripheral nerve repair in preclinical models: a systematic review of the literature. J Reconstr Microsurg 2022; ••• Epub ahead of print DOI: 10.1055/s-0041-1732432.
  • 16 Lundborg G, Dahlin LB, Danielsen N. et al. Nerve regeneration across an extended gap: a neurobiological view of nerve repair and the possible involvement of neuronotrophic factors. J Hand Surg Am 1982; 7 (06) 580-587
  • 17 Merle M, Dellon AL, Campbell JN, Chang PS. Complications from silicon-polymer intubulation of nerves. Microsurgery 1989; 10 (02) 130-133
  • 18 Sanchez Rezza A, Kulahci Y, Gorantla VS, Zor F, Drzeniek NM. Implantable biomaterials for peripheral nerve regeneration-technology trends and translational tribulations. Front Bioeng Biotechnol 2022; 10: 863969 DOI: 10.3389/fbioe.2022.863969.
  • 19 Mackinnon SE, Dellon AL. Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube. Plast Reconstr Surg 1990; 85 (03) 419-424
  • 20 Mackinnon SE, Dellon AL. A study of nerve regeneration across synthetic (Maxon) and biologic (collagen) nerve conduits for nerve gaps up to 5 cm in the primate. J Reconstr Microsurg 1990; 6 (02) 117-121
  • 21 Meek MF, Coert JH. Clinical use of nerve conduits in peripheral-nerve repair: review of the literature. J Reconstr Microsurg 2002; 18 (02) 97-109
  • 22 Meek MF, Coert JH. US Food and Drug Administration/Conformit Europe-approved absorbable nerve conduits for clinical repair of peripheral and cranial nerves. Ann Plast Surg 2008; 60 (01) 110-116
  • 23 Benga A, Zor F, Korkmaz A, Marinescu B, Gorantla V. The neurochemistry of peripheral nerve regeneration. Indian J Plast Surg 2017; 50 (01) 5-15
  • 24 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
  • 25 Cho MS, Rinker BD, Weber RV. et al. Functional outcome following nerve repair in the upper extremity using processed nerve allograft. J Hand Surg Am 2012; 37 (11) 2340-2349
  • 26 Grinsell D, Keating CP. Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. BioMed Res Int 2014; 2014: 698256
  • 27 Mackinnon SE. Technical use of synthetic conduits for nerve repair. J Hand Surg Am 2011; 36 (01) 183
  • 28 Sahin C, Karagoz H, Kulahci Y. et al. Minced nerve tissue in vein grafts used as conduits in rat tibial nerves. Ann Plast Surg 2014; 73 (05) 540-546
  • 29 Klimczak A, Siemionow M, Futoma K, Jundzill A, Patrzalek D. Assessment of immunologic, proangiogenic and neurogenic properties of human peripheral nerve epineurium for potential clinical application. Histol Histopathol 2017; 32 (11) 1197-1205
  • 30 Giusti G, Shin RH, Lee JY, Mattar TG, Bishop AT, Shin AY. The influence of nerve conduits diameter in motor nerve recovery after segmental nerve repair. Microsurgery 2014; 34 (08) 646-652
  • 31 Shin RH, Friedrich PF, Crum BA, Bishop AT, Shin AY. Treatment of a segmental nerve defect in the rat with use of bioabsorbable synthetic nerve conduits: a comparison of commercially available conduits. J Bone Joint Surg Am 2009; 91 (09) 2194-2204
  • 32 Kemp SW, Syed S, Walsh W, Zochodne DW, Midha R. Collagen nerve conduits promote enhanced axonal regeneration, schwann cell association, and neovascularization compared to silicone conduits. Tissue Eng Part A 2009; 15 (08) 1975-1988
  • 33 Moore AM, Kasukurthi R, Magill CK, Farhadi HF, Borschel GH, Mackinnon SE. Limitations of conduits in peripheral nerve repairs. Hand (N Y) 2009; 4 (02) 180-186