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International Journal of Bioprinting 3D bioprinting of nerve guidance conduits

porous nerve conduits usually have a pore size of 20–50 than 56 days. In an in vitro evaluation of dorsal root
μm and a circular, polygonal, or longitudinal shape with ganglion (DRG), the released drug maintained its biological
a certain direction to accommodate cell permeation, activity and significantly promoted neurite extension
nutrient exchange, and axonal guidance. However, pore (average length up to the level of the positive control 10
morphology and distribution are usually random due to ng/mL group). These findings suggest that this structure
the limitations of the manufacturing methods, making it holds promise as a neuroprosthetic material, offering both
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difficult to achieve a customized solution. On the contrary, topological guidance and sustained drug release. Yu et al.
3D printing can effectively overcome these limitations, utilized stamping technology to inscribe longitudinally
generating highly regular and consistent pore structures distributed grooves and ridged surfaces of 4–5 μm depth
with a high degree of reproducibility. For instance, Tao and 5 μm width on porous PCL membranes loaded with
et al. developed a low-temperature gelatin porous conduit artificial peptides. The electrophysiological recovery of
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using a 3D-printed mold to promote functional recovery the regenerated nerve was significantly enhanced in a rat
of transected peripheral nerves after nerve suturing. It was model of traction sciatic nerve injury, and the compound
reported that due to its porous structure, the conduit could muscle action potential amplitude was increased by
collapse under mechanical force and return to its original more than 50% at 4 weeks postoperatively. In parallel, in
shape after absorbing saline solution. This shape memory vitro experiments showed a significant increase in both
property simplifies the conduit installation procedure, the number of SCs adhering to the membrane and their
demonstrating the potential clinical application of porous aspect ratio, validating the effectiveness of the structural–
NGCs in facilitating nerve sutures. functional integration strategy for reconstructing nerve
architecture and function.
2.4. Micropatterned nerve conduit
Micropatterns on the inner surface of nerve conduits 2.5. Bifurcated nerve conduit
are widely used to influence cell attachment, migration, Peripheral nerves are mostly interconnected, branching
orientation, and cellular processes. One of the most used structures of varying sizes, making a single tubular
surface microstructures is the microgroove, which provides structure insufficient to meet the needs of complex nerve
topological cues to guide cell orientation and migration in repair. On the contrary, bifurcated y-shaped nerve conduits
a physical model approach. Studies have shown that the in can play an important role in inhibiting the formation of
vitro nerve sheath can recognize the topological structure traumatic neuromas after PNI, which often leads to long-
of the catheter surface and extend and grow along the term functional deficits. Although traditional fabrication
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length of microgrooves on the plane substrate. 54 methods limit the complexity of NGC structures, AM
technology has enabled the fabrication of bifurcated or
As an example, Schmalenberg et al. evaluated the y-shaped nerve conduits suitable for peripheral nerve
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ability of a microgroove-printed polymer matrix to direct bifurcations. Bolleboom et al. 3D printed a customized
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the alignment of SCs. After 4 h of cultivation, more than y-shaped conduit and an autologous nerve graft to create
47% of SCs on the micro-grooved substrate were arranged a closed loop that could induce axon regeneration into
within ± 20° of the groove direction, while SCs on the the y-shaped conduit, which accurately fitted the injured
unpatterned substrate showed random arrangements proximal nerve end. This relatively simple combined
without a clear orientation. This study found that approach prevented neuroma formation and significantly
patterned polymer matrices can enhance peripheral nerve reduced the number of axons in the middle of the
regeneration by creating a highly ordered matrix of SCs to autograft, making it suitable for unilateral PNI. Zhang
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guide neurons. Rutkowski et al. used reactive ion etching et al. demonstrated for the first time that individual nerve
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to fabricate hollow conduit lumens with microgrooves (10 stumps can form complex branching neural networks
μm width, 4.3 μm depth, 10 μm spacing). Such conduits in multi-branched nerve conduits. They utilized digital
combine a microfabricated matrix that guides axons at light processing (DLP) 3D technology with gelatin-
the cellular level with SCs that produce growth factors to methacryloyl (GelMA) to construct bifurcated nerve
promote regeneration. The biodegradable microgroove conduits and evaluated their efficacy by transferring
conduit, pre-implanted with SCs, provided physical, them from the tibial nerve to the peroneal nerve in rats.
chemical, and biological guiding cues for axon regeneration Functional and histologic evaluations showed that the
and offered a better alternative to conventional conduits, bifurcation of NGC not only promoted the regeneration
especially for repairing sciatic nerve transactions. and functional recovery of the injured peroneal nerve
Davis et al. prepared PLGA films with 10/10 μm and but also preserved a part of the function of the donor’s
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30/30 μm microgroove structures by microlithography nerve conduit. Alternatively, Hu et al. used an indirect
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that sustained the release of 3 μg/cm² of FK506 for more 3D printing technique to prepare bifurcated, multi-

Volume 11 Issue 4 (2025) 39 doi: 10.36922/IJB025140120