3D Printing and Bioprinting Nerve Conduits for Neural Tissue Engineering

Abstract

Fabrication of nerve conduits for perfectly repairing or replacing damaged peripheral nerve is an urgent demand worldwide, but it is also a formidable clinical challenge. In the last decade, with the rapid development of manufacture technologies, 3D printing and bioprinting have been becoming remarkable stars in the field of neural engineering. In this review, we explore that the biomaterial inks (hydrogels, thermoplastic, and thermoset polyesters and composite) and bioinks have been selected for 3D printing and bioprinting of peripheral nerve conduits. This review covers 3D manufacturing technologies, including extrusion printing, inkjet printing, stereolithography, and bioprinting with inclusion of cells, bioactive molecules, and drugs. Finally, an outlook on the future directions of 3D printing and 4D printing in customizable nerve therapies is presented.

Protein-Based 3D Biofabrication of Biomaterials

“…It exists in the layers of the perineurium and endoneurium as fibrils with type III and V collagen. It can be easily transformed into tubular and fibrillar structures thanks to its high extrudability [ 106 ]; Schwann cells can also adhere to it, promoting the formation of myelin [ 107 ]. Since the protein-based material of gelatin dissolves at normal human body temperature, the GelMA (gelatin modified by methacrylic acid) scaffold is considered more useful in neural tissue engineering applications [ 107 ].…”

“…It can be easily transformed into tubular and fibrillar structures thanks to its high extrudability [ 106 ]; Schwann cells can also adhere to it, promoting the formation of myelin [ 107 ]. Since the protein-based material of gelatin dissolves at normal human body temperature, the GelMA (gelatin modified by methacrylic acid) scaffold is considered more useful in neural tissue engineering applications [ 107 ]. The primary carboxyl groups of gelatin can bind amine groups of bioactive molecules, thus allowing the attachment of neurotrophic factors (NTF) which can then be gradually released during gelatin degradation [ 106 ].…”

Anisotropic scaffolds for peripheral nerve and spinal cord regeneration

“…It is nontoxic, nonimmunogenic, and FDA-approved [ 169 ]. Silk fibroin, together with many other biomaterials, has attracted a great deal of attention in the area of 3D printing nerve scaffolds [ 170 ]. However, a potential disadvantage of physically crosslinked silk fibroin hydrogels is that they are brittle, which makes them unable to undergo long range displacements and deformations [ 171 ].…”

Electrospinning Fabrication and Cytocompatibility Investigation of Nanodiamond Particles-Gelatin Fibrous Tubular Scaffolds for Nerve Regeneration

“…Ideally, NGCs should provide an equilibrium between degradation and healing rates, allow the exchange of nutrients and oxygen, while preventing the infiltration of scar tissue, and may provide guidance cues for axonal growth [ 3 ]. Micro- or nanostructured morphology, intraluminal presence of longitudinally oriented elements, or the controlled release of growth factors represent advanced strategies that may improve NGCs performances [ 4 , 5 , 6 ]. Various polymers have been investigated as scaffolds for neuronal regeneration [ 7 ], including natural polymers, such as collagen [ 8 ], gelatin [ 9 ], fibroin [ 10 ], chitosan [ 11 ], synthetic polymers, e.g., polycaprolactone [ 12 , 13 ], or hybrid blends, e.g., poly(ethylene glycol)- poly(3-caprolactone) nanoparticles, dispersed in a gelatin-methacryloyl hydrogel [ 14 ], and silk sericin/silicon [ 15 ].…”

“…Various polymers have been investigated as scaffolds for neuronal regeneration [ 7 ], including natural polymers, such as collagen [ 8 ], gelatin [ 9 ], fibroin [ 10 ], chitosan [ 11 ], synthetic polymers, e.g., polycaprolactone [ 12 , 13 ], or hybrid blends, e.g., poly(ethylene glycol)- poly(3-caprolactone) nanoparticles, dispersed in a gelatin-methacryloyl hydrogel [ 14 ], and silk sericin/silicon [ 15 ]. The strategies to fabricate NGCs range from conventional dip coating [ 9 ], and injection molding [ 8 ], up to 3D printing [ 5 , 12 , 14 ] or combined techniques, such as rolled electrospun mesh [ 10 ], and electrospun tubular scaffold filled with cryogel [ 16 ].…”