(Invited) 3D Printing and Bioprinting in Neural Tissue Engineering

Neural tissue engineering, which addresses challenges of treating disease- or injury-caused damages in the central nervous system (CNS) and peripheral nerve system (PNS) of human bodies, is advancing steadily over the past few decades. Among various innovative approaches, three-dimensional (3D) printing and bioprinting have emerged as highly promising strategies for creating customized, biomimetic scaffolds and also cell-scaffold constructs that can repair damaged nerves and promote neural tissue regeneration. Despite the impressive progress of 3D printing and bioprinting in neural tissue engineering in recent years, greater efforts are needed to develop novel and much improved neural tissue engineering products, e.g., nerve guidance conduits (NGCs), via 3D printing or bioprinting. In this paper, a comprehensive and up-to-date review of 3D printing and bioprinting in neural tissue engineering is provided. This review first introduces the structures and functions of CNS and PNS and also the injuries in these systems, as well as corresponding treatment strategies. Subsequently, advances in 3D printing and bioprinting technologies, including inkjet-based, extrusion-based, and photo-assisted bioprinting, which can be applied to neural tissue engineering, are presented and compared. Next, the biomaterials and cells as the key matrix and living components of inks and bioinks are reviewed. Afterward, the structural design of NGCs, along with topographical modifications which play key roles in guiding neural tissue regeneration, are presented and summarized. Additionally, electrically conductive scaffolds and scaffolds incorporated with biochemical cues, including neurotrophic factors such as nerve growth factor and brain-derived neurotrophic factor, which can be used to promote nerve cell differentiation and axonal extension, are also reviewed. Since ink/bioink printability and fidelity of 3D-printed structures are critical for 3D printing and bioprinting, the rheological properties and crosslinking mechanisms for bioinks are reviewed. Typical examples of applying 3D-printed/bioprinted scaffolds and constructs are shown and discussed. Our analysis, challenges and possible solutions for 3D printing and bioprinting in neural tissue engineering are systematically presented. Possible future directions, including 4D/5D printing in neural tissue engineering, in silico modeling, and in situ 3D printing, are put forward. This review helps readers to appreciate current status, understand the problems/obstacles and identify future directions of 3D printing and bioprinting in neural tissue engineering, as well as moving 3D printing and bioprinting forward toward fabricating newer and better neural tissue engineering products.