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International Journal of Bioprinting 3D bioprinting of nerve guidance conduits

in vivo by providing cells with an adhesion and degradation transplanted MSCs have shown the ability to differentiate
substrate. By employing SLA, Farzan et al. used solvent- into other support cells, such as endothelium-like cells,
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free polyurethane (PU) and different contents of PEG- smooth muscle cells, or pericytes. These endothelium-
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graphene oxides (0, 0.5, 1, 3, and 5 wt%) to prepare like cells can produce various growth factors, such as
composites. Among all samples, the composites containing vascular endothelial growth factor (VEGF), which have
5 wt% PEG-graphene oxide exhibited the highest tensile been shown to have synchronous effects on angiogenesis,
stress (3.51±0.54 MPa), tensile rupture strain (~170%), and neurogenesis, and nerve regeneration, with positive effects
compressive strength, suggesting that the addition of PEG’s on in vivo nerve regeneration. 124
functional groups improved the mechanical strength of Zhang et al. isolated a unique subpopulation of MSCs
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the conduit. Similarly, Arcaute et al. used SLA-printed from human gingival tissue and found that this cell type
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multi-lumen PEG-based NGCs, demonstrating that high tends to be induced into neural progenitor cell-like cells.
PEG concentrations, especially from 20 to 30 wt%, were In a rat model of facial segmental defect, gingival MSC
more resistant to suture pullout, with a significant increase spheres were printed as the sole cellular component using
in resistance from 0.043±0.0037 to 0.064±0.0090 N/mm.
3D bioprinting. Results indicated that axon regeneration
To summarize, it has been observed that the current and target muscle recovery reached the same level as
choice of conduit materials is shifting toward the utilization autogenous nerve transplantation at 12 weeks after
of hybrid polymers. By adjusting the composition and implantation. Cui et al. attempted to bridge the 3.5 cm
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mixing ratio of these composite materials, it is possible to dog sciatic nerve defect with a longitudinally oriented
achieve a controllable regulation of the biodegradation rate collagen catheter (LOCC) loaded with human umbilical
and mechanical strength. These adjustments may be able cord mesenchymal stem cells (hUC-MSCs). 9 months after
to meet the different needs of specific types of injuries and the operation, the connective tissue of the nerve stump at
injury gaps to promote better PNI repair and regeneration. the injured site was collected for tissue chemical analysis.
Compared with the control group, the positive signal in the
3.3. Cells and biomolecules middle ganglia of the LOCC/hUC-MSCs group was more
Assisted by certain advanced technologies, living cell intense. Transmission electron microscopy analysis of the
lines and biomolecules can now be directly used as raw thickness and size of the regenerated myelin fibers showed
materials for 3D printing. The integration of living that the LOCC/hUC-MSC group had a thicker myelin
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cells with biomaterials to form bioinks not only enhances sheath on the nerve fibers regenerated at the midpoint of
the biocompatibility of the printed constructs but also the ganglia than the LOCC group.
effectively reduces immune rejection and inflammatory
responses. In particular, the incorporation of cells can 3.3.2. Schwann cells
provide structural support derived from the native ECM, SCs are non-neuronal cells but provide support and
thereby promoting the adhesion, growth, and survival protection to neurons by forming myelin sheaths,
of neural cells and ultimately improving the efficiency constituting supportive factors for maintaining
of nerve regeneration. Moreover, specific biomolecules, homeostasis within the peripheral nervous system. In
such as neurotrophic factors and growth factors, can be PNI, SCs serve as the primary glial cells promoting axonal
co-loaded with cells into the conduit structure, where regeneration. Due to rapid phenotypic changes, they
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they play a synergistic role in regulating cellular behavior form favorable growth pathways and ultimately generate
and enhancing the efficacy of nerve repair during the myelin phospholipids around axons in response to
regeneration process. PNI. Therefore, incorporating SCs in conduits is highly
encouraged for peripheral nerve repair, and controlling
3.3.1. Stem cells their orientation through 3D bioprinting is expected to
Stem cells for NTE mainly include embryonic stem cells, effectively guide the directed growth of neurites.
induced pluripotent stem cells, NSCs, and mesenchymal
stem cells (MSCs) of different tissue sources. The induction Ning et al. developed a bioprinting process to prepare
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efficiency of NSCs greatly varies due to the heterogeneity SC-coated conduits using a novel hydrogel mixture. The
of species, age, tissues from which they are derived, and observed hydrogel microstructure and cell morphology
culture conditions. Thus, many studies have focused on revealed that the coated SCs exhibited superior
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the use of MSCs. 120,121 The use of undifferentiated MSCs performance in environments with high concentrations of
for in vivo studies allows pluripotent cells to differentiate fibronectin, as it could provide sufficient micropores and
MSCs along multiple pathways by advancing axons and fibers for cell metabolism and adhesion. Although low
natural SC stimulation. This helps to create a conducive concentrations of fibronectin could provide cell-binding
environment for nerve regeneration. In addition, fibers within the hydrogel, insufficient porosity would
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Volume 11 Issue 4 (2025) 47 doi: 10.36922/IJB025140120