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International Journal of Bioprinting 3D bioprinting of nerve guidance conduits

Table 2. Nerve guidance conduit structures and their advantages and disadvantages
Structure Structural characteristic Advantages Disadvantages Application
Hollow nerve Single hollow, no internal Simple structure, easy to Lack of morphological and Shorter nerve defects,
conduit filling manufacture, facilitates the biochemical cues; limited typically less than 5 mm;
migration of various cells and the regeneration efficiency early damage
accumulation of neurotrophic
growth factors
Multi-channel Multiple longitudinal Provides a larger surface for cell Complex structure, difficult to Medium length nerve
nerve conduit channels, simulated nerve attachment, facilitates migration of manufacture, and susceptible to defects, 5–8 mm; advanced
bundle Schwann cells, and reduces axonal permeability and degradation injuries
dispersion
Porous nerve Porosity in the conduit Allows infiltration of cells, nutrients, Excessive pore size leads to Medium length nerve
conduit wall and molecular signals, as well as deposition of fibroblasts and defects, 5–8 mm; advanced
excretion of metabolic wastes hinders axonal growth; pore injuries
distribution is often uneven
Micropatterned Microstructure with Promotes cell-directed migration High manufacturing precision; 5–10 mm; potential to
nerve conduit microgrooves, ridges, etc., and axonal alignment difficulty in fabricating repair longer nerve defects
on the inner surface and advanced injuries
Bifurcated nerve Y-shaped or multi-branch Suitable for complex nerve branch Difficult to manufacture; Bifurcated and multi-path
conduit structure repair; prevents neuroma formation requires personalized design nerves

good biocompatibility and bioactivity, and (iii) suitable good processability and easy degradation in animals.
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physicochemical properties, such as mechanical strength It has been used as an NGC material by controlling its
and structural stability. The materials for 3D-printed degradation time without the need for secondary surgical
NGCs can be categorized into natural or synthetic removal. Pure chitosan has a tensile modulus of about
polymers based on the type of embedded cells. These 20–50 MPa and a modulus of elasticity of 0.5–1.5 GPa. 73
biomaterials and representative NGC examples (Table 3) Despite the many advantages, its low strength, the absence
are discussed further. of temperature sensitivity, and its shear-thinning behavior
limit its applications in the field of biofabrication. Therefore,
3.1. Natural polymers chitosan is often used in combination with other materials
Natural polymers are macromolecular compounds present to enhance its mechanical properties and provide a more
in living organisms and have re-emerged in the last few stable conduit structure. By crosslinking chitosan with
decades as major bioactive substances due to the presence high-performance synthetic polymers such as PLA or PCL,
of biofunctionalized and bioactive molecules with the mechanical properties can be significantly enhanced.
biomimetic properties and natural recombination. Most The resulting composites typically have a tensile strength
natural materials are biocompatible and can be rapidly of 100–150 MPa and a modulus of elasticity of more than
degraded in vivo, 68–70 promoting cell adhesion, migration, 3–4 GPa, making them more suitable for application in
growth, and proliferation while avoiding the toxic effects scenarios that require high mechanical properties, such as
caused by synthetic materials. Excellent biocompatibility, nerve conduits and bone tissue engineering. For instance,
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minimal immunogenicity, and the ability to support cell Nawrotek et al. prepared chitosan/PCL conduits doped
growth make them excellent candidates for the fabrication with bioactive agent microspheres using electrodeposition
of NGCs. Chitosan, silk fibroin (SF), gelatin, and collagen combined with extrusion printing. The structural properties
are natural polymers commonly used for the 3D printing of the conduits did not change significantly during
of nerve conduits. incubation at 37°C in phosphate buffer solution (pH 7.4)
for up to 28 days, demonstrating good structural stability.
3.1.1. Chitosan Bianchini et al. prepared porous 3D-printed chitosan/
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Chitosan (and derivatives) is a biodegradable linear PCL using genipin cross-linking to improve the conduits’
polysaccharide, obtained from shrimp shells or crustaceans, physicochemical properties. The results demonstrated that
with excellent biocompatibility and antimicrobial compared to chitosan conduits, the hydration rate of the
properties. The presence of groups such as amines/aminos genipin-cross-linked conduits was significantly reduced,
and hydroxides on its molecular chain allows cells to better with the equilibrium constant of 470.3 ± 29.7%, which is
adhere and grow on its surface. In addition, chitosan has much smaller than that of the chitosan conduits (642.3

Volume 11 Issue 4 (2025) 41 doi: 10.36922/IJB025140120