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RESEARCH ARTICLE

Pre-clinical evaluation of advanced nerve guide

conduits using a novel 3D in vitro testing model

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Mehri Behbehani , Adam Glen , Caroline S. Taylor , Alexander Schuhmacher , Frederik
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Claeyssens , John W. Haycock 1
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1 Department of Materials Science and Engineering, The University of Sheffield, UK
2 Faculty of Applied Chemistry, Reutlingen University, Germany
Abstract: Autografts are the current gold standard for large peripheral nerve defects in clinics despite the frequently
occurring side effects like donor site morbidity. Hollow nerve guidance conduits (NGC) are proposed alternatives to
autografts, but failed to bridge gaps exceeding 3 cm in humans. Internal NGC guidance cues like microfibres
are believed to enhance hollow NGCs by giving additional physical support for directed regeneration of Schwann cells
and axons. In this study, we report a new 3D in vitro model that allows the evaluation of different intraluminal fibre
scaffolds inside a complete NGC. The performance of electrospun polycaprolactone (PCL) microfibres inside 5 mm
long polyethylene glycol (PEG) conduits were investigated in neuronal cell and dorsal root ganglion (DRG) cultures in
vitro. Z-stack confocal microscopy revealed the aligned orientation of neuronal cells along the fibres throughout the
whole NGC length and depth. The number of living cells in the centre of the scaffold was not significantly different to
the tissue culture plastic (TCP) control. For ex vivo analysis, DRGs were placed on top of fibre-filled NGCs to simulate
the proximal nerve stump. In 21 days of culture, Schwann cells and axons infiltrated the conduits along the microfibres
with 2.2 ± 0.37 mm and 2.1 ± 0.33 mm, respectively. We conclude that this in vitro model can help define internal NGC
scaffolds in the future by comparing different fibre materials, composites and dimensions in one setup prior to animal
testing.
Keywords: 3D model; intraluminal scaffold; peripheral nerve; regenerative medicine; microfibres

*Correspondence to: John W Haycock, Department of Materials Science and Engineering, Sir Robert Hadfield Building, Mappin Street, S1
3JD, UK; j.w.haycock@sheffield.ac.uk

Received: September 29, 2017; Accepted: November 22, 2017; Published Online: December 20, 2017
Citation: Haycock J W, 2018, Pre-clinical evaluation of advanced nerve guide conduits using a novel 3D in vitro testing model.
Int J Bioprint, 4(1): 123. http://dx.doi.org/10.18063/IJB.v4i1.123.

1. Introduction

Injuries to peripheral nerves can affect the general of complete peripheral nerve transection injuries
public in all age groups, mostly caused by domestic, comprise of surgical end-to-end suturing, allografting
industrial or traffic accidents. Severe transection or the use of nerve guidance conduits depending on
injuries are often life-changing and may result in nerve gap size and severity of injury. Despite its
defects of motor and sensory function. These injuries reputation as the gold standard, autografts suffer from
can often be repaired through a self-regeneration several major drawbacks: the sacrifice of a healthy
[1]
mechanism after Wallerian degeneration takes place . nerve, donor site morbidity, at least two surgical
However, a major concern is the increasing risk of interventions on donor and injury site, potential size
incomplete functional and motor recovery with discrepancy between harvested nerve and injured
[2]
increasing degree of injury . Current clinical treatments nerve and possible functional mismatch when treating
3D printing for drug manufacturing: A perspective on the future of pharmaceuticals. © 2018 Mehri Behbehani, et al. This is an Open Access
article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/),
permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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