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International Journal of Bioprinting 3D bioprinting of nerve guidance conduits

still constrain SC diffusion and phenotype expression. and peripheral nervous systems, especially in the later
Therefore, an appropriate porosity is a necessary condition stages of nerve regeneration, and can significantly promote
for the successful preparation of NGCs encapsulating axon growth and neural network remodeling. VEGF
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SCs. Furthermore, Ning et al. researched bioprinting provides the basis for the restoration of nutrient supply to
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SC-loaded conduits using low-viscosity hydrogel the injured area, mainly by promoting neovascularization.
components such as RGD-modified alginate, hyaluronic In vitro experiments have shown that VEGF promotes
acid, and fibronectin. Experimental results indicated the proliferation of SCs by activating signaling pathways.
that bioprinting could induce the alignment of SCs. By Related in vivo studies have shown that the number of
controlling the printing speed, the elongation of SCs could regenerated nerve fibers in the VEGF-treated group is
be effectively regulated, thereby adjusting the alignment of almost double that of the hollow conduit control group. 135
DRG neurites. As the speed increased from 4 to 9 mm/s, FGF2, also known as the basic fibroblast growth factor,
the roundness of SCs increased, and the direction of is considered to be the most important molecule in
laminin expression became more apparent. Alternatively, promoting nerve regeneration among the 23 members of
in the study of Summa et al., SCs were implanted into the fibroblast growth factor family. It has been found that
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hollow fibronectin conduits and implanted into a 10 mm the use of collagen conduits co-modified with FGF2 and
rat sciatic nerve model. Compared to control hollow ciliary neurotrophic factor significantly improved nerve
conduits, conduits filled with differentiated BMSCs, or electrophysiological function and tissue remodeling in a
conduits filled with differentiated adipose-derived stem model of long segmental defects in the nerve. 137
cells, these fibronectin-SC conduits exhibited significantly In summary, the integration of neurotrophic factors
enhanced nerve regeneration capabilities. All these into nerve conduits provides an important strategy for
evidences demonstrate the effective role played by SCs in constructing a functional nerve repair microenvironment.
nerve regeneration.
By optimizing the type, dosage, release profile, and spatial
3.4. Biomolecules distribution of these factors within the conduit structure, it
In the process of peripheral nerve repair, various types is expected to achieve precise spatial-temporal regulation
of biomolecules, especially neurotrophic factors, play of the nerve regeneration process, which can significantly
an indispensable role in promoting axon guidance, enhance the regenerative quality and clinical effects of
cell migration, SC activation, and nerve regeneration. PNI treatment.
Integrating these biomolecules into NGCs not only helps
to create a microenvironment conducive to regeneration 4. Three-dimensional bioprinting technolo-
but also serves as a key strategy to enhance the biological gies for nerve conduits
activity of the conduits, providing a more precise and A significant aspect of NGC research is the optimization
efficient intervention for the treatment of nerve injury. of technological approaches to achieve high precision and
The NGF is one of the earliest neurotrophic factors superior performance in NGC fabrication. In recent years,
discovered and mainly promotes the growth of sensory and the application of 3D printing to tissue engineering has
sympathetic nerves. In vitro experiments have demonstrated revolutionized NGC manufacturing. Among the various
that NGF promotes the survival, proliferation, and NGC biofabrication techniques, 3D bioprinting has been
synapse growth of sensory and sympathetic neurons. extensively investigated. This method is often combined
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Histological and morphological studies have shown that with 3D imaging tools to develop personalized conduits
NGF treatment significantly increases the number and with micro- or nano-scaled anatomical accuracy tailored
diameter of myelinated nerve fibers and accelerates the to the patient’s injury site. In particular, 3D bioprinting
recovery of electrophysiological parameters after sciatic allows the assembly of both biological and non-biological
nerve damage. In a 14 mm rat sciatic nerve defect model, elements in a 3D organization to produce bioengineered
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researchers utilized NGF gradient immobilization within structures for regenerative medicine, pharmacokinetics,
a nanofiber conduit to significantly guide the directional and cell biology research. This technology facilitates the
growth of DRG axons and enhance the recovery of nerve positioning and localization of cells and biomolecules
morphology and function, with results comparable to within functionalized biomaterials into inks to replicate
those of autologous nerve grafts. In addition to NGF, the complex nerve ECM and accurately mimic the
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other commonly used neurotrophic factors mainly include 3D structure of neural tissue fibers. Consequently, 3D
brain-derived neurotrophic factor, VEGF, and fibroblast bioprinting can integrate a wide range of components into
growth factor 2 (FGF2). Brain-derived neurotrophic a single printed structure, making it a powerful tool in
factor has a critical role in the repair of both the central nerve regeneration research.

Volume 11 Issue 4 (2025) 48 doi: 10.36922/IJB025140120