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International Journal of Bioprinting 3D printing technology in neurotrauma
Their results showed that EMSCs-laden scaffolds can cultured Schwann cells on 3D-printed PLGA scaffold, and
continuously release BDNF and improve neurological the construct was further applied for the treatment of SCI.
function by reconstructing the neural network after SCI in The results showed that the cell-laden scaffolds relieved
rats. 72,171 Qian et al. used the DLP 3D printing technology secondary injuries, promoted axonal growth, decreased
to print dental pulp stem cells (DPSCs) in microspheres for neuronal apoptosis and demyelination, and improved
nerve tissue regeneration. They found that the DPSCs- functional neurological recovery. Wu et al. developed
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loaded microspheres were able to promote angiogenesis a conduit by bioprinting with a composite bioink of
and repair nerve tissue structurally and functionally. Qiu gelatin, sodium alginate, and Schwann cells. The printed
et al. used the DLP technique to construct human amniotic conduit was demonstrated to promote cell adhesion and
epithelial cells (hAECs)-laden hydrogel for SCI, and their upregulate the gene expression of neurotrophic factors
later in vivo experiments showed that the neural circuit when compared with 2D culture, providing a promising
and hindlimb locomotion were partly recovered in rats. candidate for 3D-bioprinted cell-laden conduits. 179
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Hu et al. prepared a cryoGelMA conduit through indirect
printing and seeded ADSCs on the scaffold to generate the 3.4.2.2. Oligodendrocytes
bioconduit. They found that the cryoGelMA conduit Oligodendrocytes also belong to glial cells, which
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with porous structures could support the adhesion, are responsible for myelin formation in the CNS.
proliferation, and viability of ADSCs and upregulate the Oligodendrocytes can myelinate axons, thereby protecting
mRNA expressions of neurotrophic factors in vitro. They neurons. In addition, oligodendrocytes can secrete
also demonstrated that the ADSCs-loading conduit could growth factors, such as BDNF, neurotrophic factor (NT-
promote axon regeneration and functional recovery in a 10 3), and NGF, which can mediate the interaction between
mm sciatic nerve defect model. oligodendrocytes and neurons, thereby promoting axon
regeneration. Silva et al. printed a tubular scaffold using
3.4.1.3. Induced pluripotent stem cells 3D bioplotting technique, and further filled it with
Induced pluripotent stem cells (iPSCs) are a kind of oligodendrocyte-like cells. The oligodendrocytes-loaded
pluripotent stem cells formed by reprogramming fully scaffold did not cause significant inflammation, reduced
differentiated somatic cells by introducing specific secondary spinal cord injuries, and promoted axonal
transcription factors, which also have the ability to regeneration and the recovery of motor function in rat
proliferate and differentiate into a variety of tissues and SCI model. 180
organs. Due to no ethical issues involved, iPSCs are
more suitable for clinical application and are expected 3.4.3. Simultaneous transplantation of multiple
to be the preferred cell types in the field of tissue repair types of cells
and regeneration. iPSCs can easily differentiate into Stem and differentiated neural cells can simultaneously
precursor cells of all neural cell types at the injured site, be loaded in 3D-printed constructs to treat neurotrauma.
such as neural precursor cells (NPCs) and oligodendrocyte For example, simultaneous loading of NSCs and
precursor cells (OPCs). 175,176 Therefore, IPSCs may have oligodendrocytes within 3D-printed scaffolds has been
great potential in repairing nervous system injury. Fan used for neurotrauma treatment from the point of view of
et al. embedded iPSC-derived NSCs in GelMA hydrogel nerve regeneration and neuron support, respectively. Liu
for SCI, and found that the scaffold inhibited glial scars et al. customized a 3D hydrogel scaffold with hyaluronic
formation and facilitated axons regeneration. Joung et al. acid and gelatin and loaded NSCs and oligodendrocytes
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prepared iPSC-derived NPCs- and OPCs-laden hydrogel onto the scaffold. After the scaffold was implanted
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by extrusion-based 3D bioprinting, which was beneficial into SCI rats, they found that neuronal degeneration and
to the survival of transplanted cells and the reconstruction demyelination were reduced, and motor function was
of the nervous system after injury. 38 significantly restored in rats. In addition, some studies
combined BMSCs and Schwann cells for facilitating neural
3.4.2. Neural cells regeneration. Wang et al. used BMSCs, Schwann cells, and
3.4.2.1. Schwan cells GelMA hydrogels as bioink to fabricate 3D constructs.
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Schwann cells belong to glial cells, which play the role They oriented the two types of cells to enable wrapping the
of structural support in the PNS and provide a favorable outer layer of BMSCs with Schwann cells. The 3D scaffold,
microenvironment for axon regeneration. There are which precisely customizes the location of cells, plays an
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various neurotrophic factors and repair-promoting important role in differentiating BMSCs into neural cells.
proteins in the extracellular stroma secreted by Schwann The scaffold with a precise combination of multi-cells acts
cells, which are beneficial to the survival of neurons as a bridge in the injury site of SCI rats and promotes the
and the regeneration of demyelinating axons. Sun et al. reconstruction of neural functional networks. Besides,
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Volume 10 Issue 3 (2024) 76 doi: 10.36922/ijb.2311

