Additive Manufacturing of Nerve Guidance Conduits for Regeneration of Injured Peripheral Nerves

Abstract

As a common and frequent clinical disease, peripheral nerve defect has caused a serious social burden, which is characterized by poor curative effect, long course of treatment and high cost. Nerve autografting is first-line treatment of peripheral nerve injuries (PNIs) but can result in loss of function of the donor site, neuroma formation, and prolonged operative time. Nerve guidance conduit (NGC) serves as the most promising alternative to autologous transplantation, but its production process is complicated and it is difficult to effectively combine growth factors and bioactive substances. In recent years, additive manufacturing of NGCs has effectively solved the above problems due to its simple and efficient manufacturing method, and it can be used as the carrier of bioactive substances. This review examines recent advances in additive manufacture of NGCs for PNIs as well as insight into how these approaches could be improved in future studies.

Keywords: additive manufacturing; biomaterial; nerve guidance conduit; nerve regeneration; peripheral nerve.

SCHEME 1

Schematic diagram of additive manufacturing techniques for nerve guide conduit. (A) Microextrusion bioprinter. (B) Stereolithography. (C) Inkjet bioprinter. Reproduced with permission from Malda et al. (2013).

FIGURE 1

Microextrusion printing rat complex structure sciatic nerve conduit. (A) Photographs of sciatic nerve including both of sensory and motor nerve branches and (B) corresponding sciatic nerve defect. (C) Scans for 3D reconstruction from various perspectives by structured light scanning system. (D) The process of three-dimensional reconstruction of data. (E) Image after 3D reconstruction of the scan data of the sciatic nerve. (F) Image of the microextrusion printed sciatic nerve conduit. Reproduced with permission from Johnson et al. (2015).

FIGURE 2

Schematic diagram of tissue engineered NGCs by indirect bioprinting, and computer models and photographs of complex structured NGCs. (A) Schematic diagram of tissue engineered nerve conduits. (B) Computer models and photographs of (a) 4-channel, (b) bifurcating. (c) MRI scan of the human sciatic nerve and the photograph of the corresponding nerve conduit. Reproduced with permission from Hu et al. (2016).

FIGURE 3

Rapid continuous 3D printing. (A) Schematic diagram of the rapid continuous 3D printing (Zhu et al., 2018). (B) SEM images of complex structured NGCs transverse sections of hollow (a), 4-multichannel (b), aligned cryomatrix-filled NGC (c,d), random cryomatrix-filled (e), Micro-CT image of aligned cryomatrix-filled NGC (f) (Singh et al., 2018). (A) Reproduced with permission from Zhu et al. (2018) and (B) Reproduced with permission from Singh et al. (2018).

FIGURE 4

Schematic diagram of the 3D fabrication of the Col/NC/PCL NGCs, transmission electron micrograph of a sciatic nerve after surgery and the antioxidant properties of Col/NC/PCL NGCs (Qian et al., 2019). (A) The Col/NC/PCL NGC was printed in three layers from the outside to the inside, the Col layer, PCL layer, and NC/PCL layer. The inner layer was suitable for SC adhesion, and the outer layer could prevent fibroblasts from entering the conduit. (B) SEM of the Col/NC/PCL NGCs; (C) Western blot results of in vitro antioxidant and anti-inflammatory indicators; (D) Transmission electron micrograph of the sciatic nerve 18 weeks after surgery; (E) Reverse transcription-polymerase chain reaction (RT-PCR) results and the HO-1 and nuclear factor-like 2 (Nrf2) levels Reproduced with permission from Qian et al. (2019).