The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model.

Hirofumi Yurie,Manami Tsuji,Yukitoshi Kaizawa,Junichi Tajino,Tomoki Aoyama,Akira Ito,Shizuka Akieda,Hisataka Takeuchi,Ryosuke Ikeguchi,Hiroki Oda,Souichi Ohta,Koichi Nakayama,Shuichi Matsuda,Antal Nógrádi

doi:10.1371/journal.pone.0171448

Abstract

BackgroundAlthough autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit.MethodsWe developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery.ResultsKinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01).ConclusionsWe confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model.

Highlights

Treatment of peripheral nerve injury remains challenging, especially in motor nerves with long gaps [1]
Cyfuse did not have any additional role in Kinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01)
Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01)

Summary

Introduction

Treatment of peripheral nerve injury remains challenging, especially in motor nerves with long gaps [1]. Synthetic nerve conduits are associated with a risk of infection and low biocompatibility [23,24] To address these potential problems, we focused on the novel technology of Bio 3D printing, and created a completely biological, tissue-engineered, and scaffold-free conduit (Bio 3D conduit) using our novel method to create scaffold-free tubular tissue from homogeneous multicellular spheroids via a Bio-3D-printer-based system. In this system, which utilizes the cellular characteristic of self-assembly, cells cultured in a bioreactor over 24 hours aggregate to form a homogeneous multicellular spheroid structure [25]. Autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. We focused on a novel completely biological, tissue-engineered, scaffold-free conduit.

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