Protocol for a phase I trial of a novel synthetic polymer nerve conduit 'Polynerve' in participants with sensory digital nerve injury (UMANC)

Ralph Murphy, Alessandro Faroni, Jason Wong, Adam Reid, Ralph Murphy, Alessandro Faroni, Jason Wong, Adam Reid

Abstract

Background: Peripheral nerve injuries are common, with approximately 9,000 cases in the UK annually. Young working individuals are predominantly affected, leading to significant health and social implications. Functional recovery is often poor with impaired hand sensation, reduced motor function and pain and cold intolerance. Where a nerve gap exists, nerve grafting remains the gold-standard treatment but creates a second surgical site, sensory deficit at the donor site, possible neuroma formation and has limited availability. Current commercially available synthetic and resorbable nerve conduit alternatives are reported to be rigid and inflexible. This study will set out to examine the first-in-man use of a new nerve conduit device 'Polynerve' to repair small nerve gaps in digital sensory nerves of the hand. Polynerve is a degradable co-polymer of poly-ε-caprolactone and poly-l-lactic acid, which is shaped as a cylinder that has greater tensile strength, flexibility and less acidic degradation compared with current commercially available synthetic nerve conduits. In addition, it has a novel micro-grooved internal lumen that aids Schwann cell ingress and alignment to improve nerve regeneration. Methods: In total, 17 eligible participants will be recruited to undergo repair of a transected sensory nerve of the hand using the Polynerve device. All participants that receive the nerve conduit device will be followed for a period of 12 months post-surgery. The primary endpoint is safety of the device and the secondary endpoint is degree of sensory nerve regeneration through the conduit assessed using standard sensory testing (2-PD, WEST monofilament testing and locognosia). Discussion: The 'UMANC' trial is a single-centre UK-based, prospective, unblinded, phase I clinical trial of a novel nerve conduit device. We aim to demonstrate the safety of Polynerve as a synthetic, biodegradable nerve conduit and improve the treatment options available to patients with significant nerve injuries. Registration: Clinicaltrials.gov: NCT02970864; EudraCT: 2016-001667-37.

Keywords: Peripheral nerve injury; Poly-L-lactic acid; Poly-ε-caprolactone; biomaterials; nerve conduit.

Conflict of interest statement

No competing interests were disclosed.

Copyright: © 2019 Murphy R et al.

Figures

Figure 1.. Participant timeline.
Figure 1.. Participant timeline.
Figure 2.. Image of Polynerve.
Figure 2.. Image of Polynerve.
This image demonstrates a standard Polynerve device of 2 mm diameter and 22 mm long (image not to scale).

References

    1. Grinsell D, Keating CP: Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. Biomed Res Int. 2014;2014:698256. 10.1155/2014/698256
    1. Konofaos P, Ver Halen JP: Nerve repair by means of tubulization: past, present, future. J Reconstr Microsurg. 2013;29(3):149–64. 10.1055/s-0032-1333316
    1. Rosberg HE, Carlsson KS, Höjgård S, et al. : Injury to the human median and ulnar nerves in the forearm--analysis of costs for treatment and rehabilitation of 69 patients in southern Sweden. J Hand Surg Br. 2005;30(1):35–9. 10.1016/j.jhsb.2004.09.003
    1. Terzis J, Faibisoff B, Williams B: The nerve gap: suture under tension vs. graft. Plast Reconstr Surg. 1975;56(2):166–70.
    1. Daly WT, Knight AM, Wang H, et al. : Comparison and characterization of multiple biomaterial conduits for peripheral nerve repair. Biomaterials. 2013;34(34):8630–9. 10.1016/j.biomaterials.2013.07.086
    1. Wang S, Cai L: Polymers for fabricating nerve conduits. Int J Polym Sci.Hindawi;2010;2010:1–20. 10.1155/2010/138686
    1. Johnson EO, Soucacos PN: Nerve repair: experimental and clinical evaluation of biodegradable artificial nerve guides. Injury. 2008;39 Suppl 3:S30–6. 10.1016/j.injury.2008.05.018
    1. Gerth DJ, Tashiro J, Thaller SR: Clinical outcomes for Conduits and Scaffolds in peripheral nerve repair. World J Clin Cases. 2015;3(2):141–7. 10.12998/wjcc.v3.i2.141
    1. Gluck T: Ueber Neuroplastik auf dem Wege der Transplantation. Arch für Klin Chir. 1880;25:606–16.
    1. 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(5):553–72. 10.1016/j.injury.2010.12.030
    1. Jiang X, Lim SH, Mao HQ, et al. : Current applications and future perspectives of artificial nerve conduits. Exp Neurol. 2010;223(1):86–101. 10.1016/j.expneurol.2009.09.009
    1. Nectow AR, Marra KG, Kaplan DL: Biomaterials for the development of peripheral nerve guidance conduits. Tissue Eng Part B Rev. 2012;18(1):40–50. 10.1089/ten.TEB.2011.0240
    1. Tian L, Prabhakaran MP, Ramakrishna S: Strategies for regeneration of components of nervous system: scaffolds, cells and biomolecules. Regen Biomater. 2015;2(1):31–45. 10.1093/rb/rbu017
    1. Archibald SJ, Krarup C, Shefner J, et al. : A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates. J Comp Neurol. 1991;306(4):685–96. 10.1002/cne.903060410
    1. Lohmeyer JA, Siemers F, Machens HG, et al. : The clinical use of artificial nerve conduits for digital nerve repair: a prospective cohort study and literature review. J Reconstr Microsurg. 2009;25(1):55–61. 10.1055/s-0028-1103505
    1. Bushnell BD, McWilliams AD, Whitener GB, et al. : Early clinical experience with collagen nerve tubes in digital nerve repair. J Hand Surg Am. 2008;33(7):1081–7. 10.1016/j.jhsa.2008.03.015
    1. Wangensteen KJ, Kalliainen LK: Collagen tube conduits in peripheral nerve repair: a retrospective analysis. Hand (N Y). 2010;5(3):273–7. 10.1007/s11552-009-9245-0
    1. Taras JS, Nanavati V, Steelman P: Nerve conduits. J Hand Ther. 2005;18(2):191–7. 10.1197/j.jht.2005.02.012
    1. Weber RA, Breidenbach WC, Brown RE, et al. : A randomized prospective study of polyglycolic acid conduits for digital nerve reconstruction in humans. Plast Reconstr Surg. 2000;106(5):1036–45; discussion 1046-8. 10.1097/00006534-200010000-00013
    1. Bertleff MJ, Meek MF, Nicolai JP: A prospective clinical evaluation of biodegradable neurolac nerve guides for sensory nerve repair in the hand. J Hand Surg Am. 2005;30(3):513–8. 10.1016/j.jhsa.2004.12.009
    1. Sun M, McGowan M, Kingham PJ, et al. : Novel thin-walled nerve conduit with microgrooved surface patterns for enhanced peripheral nerve repair. J Mater Sci Mater Med. 2010;21(10):2765–74. 10.1007/s10856-010-4120-7
    1. Mobasseri A, Faroni A, Minogue BM, et al. : Polymer scaffolds with preferential parallel grooves enhance nerve regeneration. Tissue Eng Part A. 2015;21(5–6):1152–62. 10.1089/ten.TEA.2014.0266
    1. Mobasseri SA, Terenghi G, Downes S: Schwann cell interactions with polymer films are affected by groove geometry and film hydrophilicity. Biomed Mater. 2014;9(5):055004. 10.1088/1748-6041/9/5/055004
    1. Murphy R, Reid A: A phase I trial of a novel synthetic polymer nerve conduit "Polynerve" in participants with sensory digital nerve injury (UMANC).2019. 10.17605/
    1. Clavien PA, Barkun J, de Oliveira ML, et al. : The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96. 10.1097/SLA.0b013e3181b13ca2
    1. Safety reporting - Health Research Authority.
    1. Dellon AL: Sensibility,re-education of sensation in the hand. Baltimore: Williams & Wilkins;1981.
    1. Weinstein S: Fifty years of somatosensory research: from the Semmes-Weinstein monofilaments to the Weinstein Enhanced Sensory Test. J Hand Ther. 1993;6(1):11–22; discussion 50. 10.1016/S0894-1130(12)80176-1
    1. : A Systematic Review of Sensory Outcomes of Digital Nerve Gap Reconstruction With Autograft, Allograft, and Conduit. Ann Plast Surg.82(4S Suppl 3) : 10.1097/SAP.0000000000001851 S247-S255 10.1097/SAP.0000000000001851
    1. : Nerve wrap after end-to-end and tension-free neurorrhaphy attenuates neuropathic pain: A prospective study based on cohorts of digit replantation. Scientific Reports.2018;8(1) : 10.1038/s41598-017-19134-8 10.1038/s41598-017-19134-8
    1. : Enhancing the Outcome of Traumatic Sensory Nerve Lesions of the Hand by Additional Use of a Chitosan Nerve Tube in Primary Nerve Repair: A Randomized Controlled Bicentric Trial. Plast Reconstr Surg.142(2) : 10.1097/PRS.0000000000004574 415-424 10.1097/PRS.0000000000004574
    1. : Refinements of nerve repair with connector-assisted coaptation. Microsurgery.2017;37(3) : 10.1002/micr.30151 256-263 10.1002/micr.30151
    1. : Decellularized Nerves for Upper Limb Nerve Reconstruction: A Systematic Review of Functional Outcomes. J Reconstr Microsurg.2015;31(9) : 10.1055/s-0035-1558463 660-7 10.1055/s-0035-1558463

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