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International Journal of Bioprinting 3D bioprinting of nerve guidance conduits
± 31.6%; p < 0.01). The degradation rate of the conduit a guiding effect and bridged a 15 mm peripheral nerve
was significantly reduced, and the structural stability was defect in rats; myelinated nerve regeneration was observed
enhanced. Zhang et al. utilized chitosan/neurotrophic at 8 weeks postoperatively, showing good nerve repair.
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factor-3 for the 3D-printed topology micron track conduit Yoo et al. successfully 3D-printed a natural, unmodified
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to induce targeted growth of SCs, showing a higher growth collagen nerve conduit using a dense collagen solution
density of primary SCs on micron track conduit compared and implanted it into a rat nerve model. 6 weeks after
to commercial conduits, which effectively facilitated the implantation, the 3D-printed NGC showed a denser
functional recovery of a 15 mm gap nerve injury model and more organized pattern of regenerating axons.
in rats. Morphometric analysis of nerve sections distal to the
repair site at 12 weeks showed that myelinated axon counts
3.1.2. Silk fibroin and myelin thickness were higher in the 3D-printed group
SF is obtained from silkworm silk, which is a rich than in the control group, confirming the beneficial effects
natural source of proteins with outstanding mechanical of 3D-printed collagen on axonal regeneration, myelin
properties, biodegradability, biocompatibility, and sheath regeneration, and nerve cells’ functional recovery.
bioabsorbability. 77–79 Silk can be processed in the form of However, the main drawbacks of collagen are its high
films, gels, nets, etc., having a wide range of applications in cost, poor mechanical properties, and limited stability, as
NTE, especially using electrospinning. For instance, both it can only remain liquid at low temperatures. To address
Dinis et al. and Zhao et al. electrospun SF-based 3D this limitation, cross-linking or combining collagen with
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NGCs. SF-NGCs had an ultimate peak stress of 4.0±0.6 MPa synthetic materials is often necessary. For instance, Chen
and a corresponding elongation at failure of 156.8±46.7%, et al. fabricated porous 3D-printed collagen/SF (C/S)
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demonstrating that the SF-NGCs exhibited a mechanical conduits adsorbed with secretome (ST) derived from
behavior comparable to that of rat sciatic nerve, good human umbilical mesenchymal stem cells (3D-C/S+ST).
clinical application performance, and potential to promote After co-culture with NSC, 3D-C/S+ST showed good
nerve regeneration and functional recovery. Wang et al. cytocompatibility, and infrared spectroscopy data showed
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combined electrostatic spinning, braiding, and coating that 3D-C/S+ST had appropriate lipid-soluble and water-
techniques to prepare a composite sericin protein NGC, soluble chemical bonds suitable for neuronal cell adhesion
which was implanted into a 10 mm nerve defect in rats. and growth. From X-ray diffraction analysis, 3D-C/S+ST
There was no obvious inflammatory reaction after 8 also showed a desirable crystallinity, hence better control
weeks of implantation. Apparent axonal and myelin tissue of the rate of degradation. Therefore, the development
appeared inside the conduit group at 12 weeks and directly of collagen-based composites for NGC fabrication is a
throughout the conduit tissue, indicating successful common procedure to be considered.
regeneration of the rat sciatic nerve within the conduit.
Alternatively, Zhao et al. prepared composite polypyrrole 3.1.4. Gelatin methacrylate
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(PPy)/SF conduits cultured with SCs by combining 3D Gelatin is a natural polymer derived from collagen and
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bioprinting with electrospinning. The results showed that has excellent biocompatibility, hemostatic properties, low
SCs mainly adhered to the surface of the conduits and cytotoxicity, and antigenicity, and promotes cell attachment
maintained normal morphology (full, pike-shaped, and and growth. However, its mechanical properties and
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shiny), good interconnection, and good proliferation. This antimicrobial activity are relatively poor, with a tensile
indicated that the composite PPy/SF conduit promoted strength that is generally 0.05–0.5 MPa. 89,90 Therefore,
SC adhesion, differentiation, and proliferation. However, it often needs to be crosslinked with other polymers
obtaining SF is a complex and expensive process that to promote its mechanical performance. GelMA is a
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demands specialized methods and resources. Moreover, gelatin-based biomaterial chemically modified to promote
variations in silk sources and processing parameters can cell adhesion, growth, and degradation. GelMA has better
affect the material’s quality and consistency. mechanical tunability and structural stability than ordinary
gelatin. Its mechanical strength and degradation rate are
3.1.3. Collagen
Collagen is the most abundant protein in mammals, with dependent on many factors, such as gelatin concentration,
good biocompatibility, high stability, and the capability to degree of methacrylation, and photo-crosslinking.
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promote axonal regeneration and myelination. Collagen Gong et al. proposed a hollow porous GelMA/
types I and II are the key components of peripheral nerves. Engelbreth–Holm–Swarm (EHS) NGC with 89.8%
Several studies explored collagen and its derivatives as the porosity, 167.6 μm pore diameter, 0.489 kPa tensile
main material for the biofabrication of NGC. For instance, modulus, and 0.314 kPa compressive modulus. 16 weeks
Fujimaki et al. developed a collagen-based NGC with after implantation in rats, hematoxylin and eosin staining
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Volume 11 Issue 4 (2025) 44 doi: 10.36922/IJB025140120