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International Journal of Bioprinting 3D bioprinting of nerve guidance conduits

of the gastrocnemius muscle showed that there was no properties. Commonly used biodegradable synthetic
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significant difference between the autograft group and polymers include PLA, PCL, PLGA, and polyethylene
the composite conduit group, confirming that the EHS glycol (PEG). Non-degradable materials are instead less
filling accelerated the repair of nerve defects. Tao et al. commonly used due to induced chronic foreign body
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3D printed hollow GelMA hydrogels with drug-loaded reaction, which inhibits the recovery of peripheral nerve
poly(ethylene glycol)-poly(3-caprolactone) nanoparticles function and requires a secondary surgical procedure to
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to obtain a physical microenvironment for axon remove them.
extension and drug release for nerve regeneration. In vitro
experiments showed that the migration of SCs increased 3.2.1. Polylactic acid
with the drug concentration. The conduit was placed into PLA is a biodegradable thermoplastic aliphatic polyester
rats, and the functional recovery of injured peripheral derived from plants and contains repeating lactic acid
units that promote the proliferation, migration, and
nerves was detected through electrophysiology. The results maturation of myelinated axons. 96,97 The Young’s modulus
showed that the efficacy of the 3D-printed conduits was (around 4.1 GPa) and tensile strength (around 62.7 MPa)
comparable to that of autografts, having a good clinical
application value. Liu et al. also repaired a bilayer of PLA are significantly higher than most synthetic conduit
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NGC using GelMA/bone marrow mesenchymal stem materials, implying that PLA-based NGCs can effectively
maintain morphology and support nerve regeneration in
cells (BMSCs)/gelatin, which resulted in a high survival complex in vivo environments. Its degradation product is
rate and extensive morphological expansion of BMSCs lactic acid, which can be rapidly metabolized by the body,
encapsulated in the inner layer. The density and value- but its poor cell adhesion and high hydrophobicity limit
added rate of PC12 cells attached to the cellularized bilayer its application. 98,99 Gerdefaramarzi et al. fabricated PLA/
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NGCs were four and nine times higher than those of the PCL/graphene nanocomposite conduits for peripheral
non-cellularized bilayer NGCs, respectively. These results NTE using a fused filament fabrication 3D printing
suggested that the 3D bioprinting of BMSCs embedded method, which showed porosity and pore sizes in the
in bilayer NGCs has great potential to promote peripheral range of 50– 86% and 300–500 µm, respectively. The elastic
nerve repair. Another example is reported by Ye et al., modulus of the scaffolds was approximately 22.36 MPa,
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which exploited photocurable GelMA to fabricate multi- which is suitable for peripheral nerve tissue applications,
channel NGCs using DLP technology. Neural crest stem and the degradation rate in phosphate buffer solution was
cells cultured on the GelMA NGC showed good survival, 0.14 mm/day, which is very close to the regeneration rate
proliferation, and migration rates. of peripheral nerve tissue. These findings suggest that PLA/
In summary, although most natural polymers PCL/graphene oxide conduits are promising for peripheral
exhibit low cytotoxicity and possess unique biological NTE. Wang et al. also prepared a composite NGC using
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advantages, such as the antibacterial activity of chitosan chitosan/PLA and used it for bridging long segments of
and the neuroregenerative potential of collagen, they peripheral nerve deficits. The results showed that 6 months
still face several challenges in practical applications. after grafting, innervation was restored to the target muscles
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Some of these challenges include poor mechanical and limb mobility was improved. Alternatively, Yue et al.
strength, uncontrollable degradation rates, and complex prepared film-based surfaces with micro-grooved NGCs
processing and purification procedures. To overcome on PCL/PLA using micro-stereolithography (SLA). Young’s
these limitations, current research should focus on modulus of PCL/PLA films (~109.6 MPa) was higher than
modifying natural polymers through chemical or physical that of PCL films (~56.7 MPa), which indicated that the
approaches to enhance mechanical properties and achieve stiffness and deformation resistance of PCL/PLA were
more controllable degradation profiles while preserving improved. PCL/PLA samples showed a higher human
inherent biocompatibility and bioactivity. This could help neuroblastoma cell proliferation than PCL and longer
in improving the applicability of natural polymers in nerve cellular lengths (~275 µm), which was higher than that of
conduits and other areas of regenerative medicine. control PCL films (~200 µm). Hence, this facile fabrication
method is promising for the fabrication of morphology-
3.2. Synthetic polymers guided cues. Zheng et al. developed a combinatorial
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Synthetic polymers are artificial polymers with adjustable NGC consisting of longitudinally aligned electrospun
chemical structures and physical properties, categorized nanofibers and porcine decellularized nerve matrix
into degradable and non-degradable materials. Degradable hydrogel. The in vivo capacity for facilitating nerve tissue
materials have been widely used due to their material’s regeneration and functional recovery was evaluated in a
inherent plasticity, wide range of sources, lower cost, rat sciatic nerve defect model. PLA-aligned/0.25% porcine
good biocompatibility, and controllable physicochemical decellularized nerve matrix hydrogel scaffold exhibited the

Volume 11 Issue 4 (2025) 45 doi: 10.36922/IJB025140120