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International Journal of Bioprinting 3D printing technology in neurotrauma

the differentiation of stem cells into neurons rather than channel conduits could effectively guide the proximal
glial cells. 122 ends to regenerate directionally along the microchannel
to connect with the distal ends in a mouse nerve defect
3.2.2. Electric stimulation model. The functional and histological assessments
Electrical stimulation can regulate stem cell migration indicate that this conduit can promote axon regeneration
and differentiation through its polarity characteristics. and functional recovery. Meanwhile, Qian et al. prepared
Previous studies have found that pulsed DC stimulation porous conduits using microneedles to generate
of 1 V/cm effectively enhances the differentiation of multiple aligned macropores (50 μm) on the wall of the
NSCs into neurons. Many studies have demonstrated conduit, 109,134 to promote nutrient exchange during the
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regulating the electrical stimulation through conductive regeneration process. Moreover, longitudinal topography
materials can promote the proliferation, differentiation, of the inner wall of the conduit has also been reported
and neurite elongation of NSCs. 124,125 The effect of electrical to be beneficial for nerve regeneration. For example,
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stimulation is more significant in a 3D culture environment, through laser-based micro SLA, Pateman et al. developed
specifically reflected in higher expression levels of neuron- PEG-DA hydrogel conduits with inner microgroove
related genes, and more stem cells differentiate into structures (50 μm). This conduit could promote the dorsal
nerve cells under electrical stimulation. 126,127 Heo et al. root ganglion to proliferate, differentiate, and orientate in
combined dorsal root ganglion (DRG) cells and GelMA vitro and support nerve re-connection through a 3 mm
with a conductive structure (crystallized PEDOT: PSS) to defect. When the PNI involves the loss of a branch point,
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create a 3D conductive scaffold, which can promote the the branch structure should be designed to match the
differentiation of encapsulated DRG cells into neurons anatomical structure. Johnson et al. fabricated a Y-shape
under electrical stimulation. In a similar way, Song conduit through an extrusion printing process based on
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et al. prepared conductive scaffolds loaded with NSCs the 3D models, designed by 3D scanning patients’ nerve
through 3D bioprinting and confirmed the differentiation anatomies. They also demonstrated that the bifurcating
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of NSCs on the scaffolds into neurons. The scaffolds conduits with customized geometries and growth factor
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can reduce glial scar formation when implanted in SCI gradients could guide the injured stumps to regenerate
rats. Vijayavenkataraman et al. combined synthetic across a complex nerve defect (10 mm, bifurcated) and
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polymer PCL and conductive polymers (polypyrrole, poly result in improved functional recovery. Meanwhile, Zhu
(acrylic acid)) to fabricate conductive conduits through et al. also constructed a life-size triple-branched conduit
inkjet 3D printing. They found that the conductive based on the complex structure of the human facial
conduits can promote neuronal cell proliferation and nerve, demonstrating the great potential of 3D printing
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differentiation. 130-133 In addition, carbon-based conductive for different nervous system injuries.
materials, such as graphene, also have the potential to be
integrated into conduits for PNI. Qian et al. fabricated 3.3. Bioactive substances
RGD and polydopamine (PDA)-coated PCL/GO 3.3.1. Small-molecule compounds
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conduits through an integrated 3D printing method. Small-molecule compounds have unique advantages
The electrically conductive and cell-adhesive conduits such as high cell permeability, good reversibility, and easy
could promote neural expression, axon regeneration, and control of cell fate. Combining them with 3D-printed
remyelination for PNI in vivo. constructs such as microneedle arrays, conduits, scaffolds,
3.2.3. Biomimic structures etc. has become a new strategy for regulating cell fate in
For neurotrauma, the biomimetic structure is nervous system injuries.
important for providing physical cues to build a In the treatment of CNS injury, Huang et al. encapsulated
favorable microenvironment for axon regeneration and the traditional anti-inflammatory drug dexamethasone
remyelination. Generally, the structure design of conduits (Dexa) in a polypyrrole-coated microneedle array using the
involves the specific architectures of the lumen, the wall, TPP method to achieve electronically controlled release of
and the branch of conduits, which were biomimetic to dexamethasone. This high-precision microneedle array
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the anatomical structures and properties of the natural can be placed under the dura mater to achieve electronically
nerves. 3D printing technology has provided an advanced controlled sustained release of Dexa, thereby reducing the
tool for fabricating conduits with customized and complex inflammatory response mediated by microglia. Some new
structures. To mimic the structure of nerve fascicles and anti-inflammatory drugs are also applied in 3D-printed
reduce the axon mismatch, Zhu et al. fabricated multi- scaffolds for CNS injury. Oxymatrine (OMT) is the main
channel conduits through a rapid continuous DLP bioactive component of traditional Chinese medicine
printing process. They demonstrated that the multi- Sophora flavescent Ait. It has been proven to have anti-
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Volume 10 Issue 3 (2024) 73 doi: 10.36922/ijb.2311