3D Bioprinting for Spinal Cord Injury Repair

Abstract

Spinal cord injury (SCI) is considered to be one of the most challenging central nervous system injuries. The poor regeneration of nerve cells and the formation of scar tissue after injury make it difficult to recover the function of the nervous system. With the development of tissue engineering, three-dimensional (3D) bioprinting has attracted extensive attention because it can accurately print complex structures. At the same time, the technology of blending and printing cells and related cytokines has gradually been matured. Using this technology, complex biological scaffolds with accurate cell localization can be manufactured. Therefore, this technology has a certain potential in the repair of the nervous system, especially the spinal cord. So far, this review focuses on the progress of tissue engineering of the spinal cord, landmark 3D bioprinting methods, and landmark 3D bioprinting applications of the spinal cord in recent years.

Keywords: 3D bioprinting; hydrogels; neural system tissue engineering; scaffolds; spinal cord injury repair.

FIGURE 1

Schematic diagrams demonstrating bioprinting methods. (A) Thermal and piezoelectric inkjet-based bioprinting. (B) Extrusion-based bioprinting (pneumatic pressure, piston, and screw). (C) Laser-assisted bioprinting. (D) SLA bioprinting and DLP bioprinting.

FIGURE 2

(A) PEGDA/GELMA hydrogel-based spinal cord scaffolds are printed, the gray matter is printed as a solid. The scaffold mimics the linear organization of white matter. Channels are precisely printed in 3D space. (B) Schematic diagram explaining the axonal alignment and guidance hypothesis. Channels in the scaffold provide linear guidance of rostral–caudal planes, so that grafted cells and host cells can be connected linearly. The host original axons regenerate in the scaffold and form synaptic connections with the neurons in the scaffold. The axons in the scaffold continue to extend to the lesion and form a functional connection at the caudal side of the host lesion. (C) Channels are filled with GFP-expressing NPCs. (D) Implanted GFP-expressing NSCs extend linear axons within the scaffold. Rostral is to the left and caudal is to the right. (E) Rostral entrance to the channel is penetrated by labeled NF host axons. Reproduced with permission from Koffler et al. (2019).

FIGURE 3

(A) Live/dead staining of NSCs within the 3D bioprinted NSC-laden HBC/HA/MA scaffold cultured for 0 days (left) and 7 days (right), respectively. High cell viability can be observed. (B) Proliferation of NSCs in the 3D bioprinted scaffold after culture for 1, 3, and 7 days (C) General diagram of the 3D bioprinted scaffold and the implantation of the scaffold into the gap of SCI lesion. (D) BBB score after the implantation of the scaffold for different weeks. Reproduced with permission from Liu et al. (2021).