3D Printed Polymeric Hydrogels for Nerve Regeneration

Abstract

The human nervous system lacks an inherent ability to regenerate its components upon damage or diseased conditions. During the last decade, this has motivated the development of a number of strategies for nerve regeneration. However, most of those approaches have not been used in clinical applications till today. For instance, although biomaterial-based scaffolds have been extensively used for nerve reparation, the lack of more customized structures have hampered their use in vivo. This highlight focuses mainly on how 3D bioprinting technology, using polymeric hydrogels as bio-inks, can be used for the development of new nerve guidance channels or devices for peripheral nerve cell regeneration. In this concise contribution, some of the most recent and representative examples are highlighted to discuss the challenges involved in various aspects of 3D bioprinting for nerve cell regeneration, specifically when using polymeric hydrogels.

Keywords: 3D printing; nerve regeneration; polymeric hydrogels.

Figure 1

Schematic representation of 3D printing, (A) transection of complex nerve (B) Imaging of transected nerve (C) functionalization of the 3D printed model with physical cues, and path-specific biochemical cues. Adapted with permission from ref. [31]. Copyright 2015, Wiley-VCH.

Figure 2

(A) Schematic of implanted nerve guide showing bifurcation into sensory and motor nerve paths. (B) Photograph of an implanted 3D printed nerve guide prior to suturing. Adapted with permission from ref. [31]. Copyright 2015, Wiley-VCH.

Figure 3

(A) Bio 3D conduit was implanted into the nerve defect, and the proximal and distal nerve stumps were secured 1.5 mm into the tube to create a 5-mm interstump gap in the conduit. (B) The silicone tube with 8 mm length was implanted in the same procedure. (C) Regenerated sciatic nerve eight weeks after surgery in the bio 3D group and (D) silicone tube. Scale bar in (C,D) = 5 mm. Adapted with permission from ref. [32]. Copyright 2017, Public Library of Science.

Figure 4

Schematic presentation of the 3D engineered bio-conduit for peripheral nerve regeneration. Adapted with permission from ref. [33]. Copyright 2016, Nature Publishing Group.

Figure 5

(A) Scheme of a representative 3DNSC for peripheral nervous system applications, showing (1) PNS neurons in chamber 1, (2) Schwann cells in chamber 2, and (3) terminal cell junctions in chamber 3. The Schwann cells and the terminal cells interact with the neurons and each other solely via the axonal network. (B) Circular pattern of 3D printed silicone microchannels for axonal guidance in the center of a plastic 35 mm dish. (C) A 3DNSC showing perpendicular assembly of microchannel and tri-chamber components. Adapted with permission from ref. [34]. Copyright 2016, The Royal Society of Chemistry.