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International Journal of Bioprinting 3D printing technology in neurotrauma

for the long-term nerve regeneration and significantly nerve injury, neural stem cell transplantation can reduce
improved peripheral nerve recovery in vivo. the inflammatory response, prevent cell apoptosis, inhibit
the formation of glial scars, and shrink the injury cavity,
3.3.3. Exosomes thereby promoting the recovery of electrophysiological
Exosomes originate from endosomes and are extracellular activities and sensorimotor functions after injury. 160,161
vesicles with a diameter of 40–160 nm and an average However, transplanting NSCs directly into damaged
diameter of 100 nm. The multivesicular bodies can fuse areas has limited therapeutic effect, which may be due
with the cell membrane and release the vesicles from the to the difficulty of stem cells surviving and uncontrolled
cell to the ECM, so exosomes often contain substances differentiation. 3D-printed constructs can provide a
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such as lipids, proteins, DNA, RNA, and microRNAs. conducive microenvironment for stem cells survival,
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The function of exosomes depends on their cell or tissue proliferation, and differentiation in the injured areas.
source and can participate in multiple pathophysiological Koffler et al. printed a precision-tailored 3D scaffold via
processes, such as immune response, antigen presentation, a microscale continuous projection printing technology
programmed cell death, angiogenesis, inflammation, (μCPP) ladened with NPCs. In rat SCI model, the
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and coagulation. Liu et al. prepared low-temperature scaffold promoted axons extension into the 3D scaffold
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3D-printed collagen/chitosan scaffolds loaded with and regeneration to caudal side of the injured spinal cord,
exosomes derived from NSCs pretreated with insulin 163
growth factor-1. Their strategy of 3D printing scaffold and significantly improved the functional outcomes. Liu
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combined with exosomes can improve the neurological et al. fabricated NSC-laden scaffolds by 3D bioprinting.
function of TBI rats by recruiting stem cells, reducing The 3D biomimetic scaffold is beneficial to the survival
inflammation, promoting angiogenesis, etc. Besides, and differentiation of NSCs cells into neurons because
they also designed a hypoxia-pretreated EMSC-derived it simulates the natural environment of the spinal cord,
exosomes-loaded bioprinting scaffold. In TBI beagle dogs, promoting nerve regeneration and motor function
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this exosomes-loaded scaffold plays an important role in recovery. Besides, Yang et al. created NSCs-laden
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anti-inflammation, promoting nerve regeneration and scaffolds via extrusion-based 3D bioprinting. NSCs were
improving the motor ability. 155 wrapped in an ECM-like hydrogel to form a 3D nerve
fiber-like structure. The NCSs in the scaffold survived and
3.4. Cell transplantation improved the microenvironment in the injured site, and
3.4.1. Stem cells subsequently promoted nerve regeneration, the formation
Stem cells are multipotent cells with the ability to self- of nerve relay, and effective motor function recovery
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replicate, differentiate, and repair damaged tissue. Stem in rats. As for PNI, Li et al. prepared a bionic scaffold
cells have been incorporated in neurotrauma treatment with longitudinal fibers by a 3D printing technology and
because they release neurotrophic factors and promote combined the scaffold with neural crest stem cells (NSCs)-
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neurovascular unit reconstruction in neural tissue derived Schwann cell progenitors. They found that the
repair. The combination of 3D printing technology and cell-loading scaffold could promote directional cell growth
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stem cell transplantation can more effectively improve and axonal myelination in vitro, and facilitate nerve
the function outcome after neurotrauma. 3D printing regeneration and functional recovery in vivo.
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combined with stem cell transplantation increases cell 3.4.1.2. Mesenchymal stem cells
proliferation and neural differentiation. Besides, it reduces Mesenchymal stem cells (MSCs) originate from mesoderm
inflammatory response and shrinks the cavities after and ectoderm in the early stages of development and
neurotrauma. Stem cells such as neural stem/progenitor have various types, including bone (BMSCs), amniotic
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cells, induced pluripotent stem cells, and mesenchymal membrane (hAMSCs), adipose (ADSCs), and dental
stem cells have been combined with 3D printing for pulp (DP-MSCs). MSCs are also pluripotent stem cells
neurotrauma treatment.
and can replicate and differentiate themselves. 167,168 In
3.4.1.1. Neural stem cells/neural progenitor cells addition, MSCs can secrete cytokines such as nerve
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Neural stem cells (NSCs)/neural progenitor cells (NPCs) growth factors. MSCs have shown great potential in
are multipotent stem cells with the ability to self-renew. the field of tissue repair and regeneration due to their
They can differentiate into neurons, astrocytes, and high availability, pleiotropic effects, immunomodulation,
oligodendrocytes, and can pass through the blood–brain self-regeneration, easy isolation, and culture in damaged
barrier, thereby replacing damaged cells at the injury site. tissues. Li et al. and Chen et al. fabricated EMSCs-
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Moreover, they can secrete a variety of chemokines and loaded sodium alginate-Matrigel (SAMA) hydrogel and
neurotrophic factors to benefit nerve regeneration. After collagen/silk fibroin by 3D bioprinting, respectively. 72,171
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Volume 10 Issue 3 (2024) 75 doi: 10.36922/ijb.2311