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International Journal of Bioprinting 3D printing technology in neurotrauma
regeneration of the whole tissue. In addition, the arginine- 3.1.1.3. Chitosan
glycine-aspartic acid (RGD) sequence in collagen is able Chitosan is a natural polysaccharide extracted from the
to influence stem cells, and the collagen scaffold could exoskeleton of crustaceans, squid cartilage, or fungal cell
promote cell adhesion, proliferation, and differentiation. walls. It has good mechanical strength and can carry bioactive
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However, the scaffolds made of collagen alone face several substances to treat neurotrauma. In the field of peripheral
problems, such as insufficient mechanical strength and nerve regeneration, it has been proven that chitosan can
too rapid degradation. Chen et al. crosslinked collagen be used for nerve regeneration and reduction of fibrous
and heparin sulfate, a kind of linear polysaccharide of the scar tissue. 95,96 Chitosan may be beneficial to neurotrauma
glycosaminoglycan family, and produced a 3D-collagen/ because its degradation product chitooligosaccharides can
heparin sulfate by extrusion printing. They found that promote the migration of macrophages to the injured site
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implanting this scaffold into SCI rats could increase the and reshape the microenvironment of the injured nerve.
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number of neurofilament-positive cells, reduce cavities, Sun et al. designed a chitosan-containing scaffold to repair
and restore motor function. Similarly, Jiang et al. applied SCI by a 3D extrusion printing method. Histologically,
a collagen scaffold made by extrusion bioprinting into this scaffold reduced glial scar and promoted axonal
beagle TBI models. The scaffold exhibited good physical regeneration. Functionally, it promoted the recovery of
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properties and biocompatibility and promoted structural motor function in rats. 98
and functional reconstruction after brain injury in
beagles. Wang et al. constructed a multichannel collagen 3.1.1.4. Gelatin
scaffold with a multi-nozzle 3D printing technology Gelatin is obtained from collagen and converted into
and found that the mechanical properties of the conduit gelatin through high temperature, chemical denaturation,
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could vary with the concentration of collagen. They or enzymatic treatment. Gelatin is a biocompatible and
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reported that 5% collagen was optimal for nerve scaffold degradable polymer that is easily soluble in water and can
fabrication based on the mechanical properties and form hydrogels with heat-sensitive retention properties.
printing performances. Raising the temperature can turn it into a liquid by
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weakening hydrogen bonds. Therefore, the gelatin material
3.1.1.2. Silk fibroin can be formed into various shapes suitable for nervous
Silk fibroin (SF) is a natural macromolecular protein system. Tran et al. synthesized gelatin methacrylate
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polymer with inherent advantages, such as good (GelMA) by adding methacrylic anhydride to gelatin
mechanical properties, biocompatibility, biodegradability, in a carbonate/bicarbonate buffer. Next, they used an
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and low immunogenicity when forming different improved digital light processing (DLP) technique to
materials. 89,90 SF has the characteristics of high mechanical prepare GelMA scaffolds with heterogeneous mechanical
strength, good elasticity, and good environmental properties, and simulate the gray and white matter
stability, which can improve the shortcomings of collagen. structures of the spinal cord for SCI repair. Regarding
Li et al. used the extrusion bioprinting method to make peripheral nerve injuries, Tao et al. used GelMA to
a biomaterial scaffold made of SF and collagen, which fabricate hydrogel conduits in a continuous DLP printing
combines the advantages of high mechanical strength and process. They found that the GelMA hydrogel conduits
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SF stability, simulating white matter tracts in the spinal were compatible with HUVECs and Schwann cells.
cord. Moreover, the biomimetic scaffold containing SF
can guide nerve regeneration and reconstruct neural 3.1.1.5. Decellularized extracellular matrix
functional networks in SCI rats. Kim et al. synthesized Decellularized extracellular matrix is derived from natural
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silk fibroin glycidyl methacrylate (SF-MA) able to form tissue and is prepared by removing cells from the tissue
hydrogels through DLP printing, which is promising while retaining functional ECM components. It has a good
for fabricating hydrogel conduits with good mechanical function of promoting cell adhesion and is easy to form a
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properties. However, the Bombyx mori SF lacks cell- hydrogel by thermal crosslinking. These characteristics
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adhesive motifs and is not beneficial for the adhesion make it particularly suitable for preparing constructs by
and proliferation of Schwann cells. Meanwhile, Zhang 3D printing to treat neurotrauma. For example, Bae et
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et al. reported a bioink based on Antheraea pernyi silk al. prepared brain dECM to carry NSCs and fabricated
fibroin (ASF) which contains cell-attachable sequence scaffolds through 3D printing for implantation in TBI
RGD for DLP printing. The developed ASF hydrogel rats. The results showed that NSCs proliferated and
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displayed good mechanical properties and positive effects differentiated well in dECM, and the scaffold was helpful
on Schwann cell’s adhesion, proliferation, and migration, in reducing neuroinflammation in TBI rats. Similarly,
and holds potential for application in PNI treatment. Kong et al. used porcine CNS tissue to prepare dECM
Volume 10 Issue 3 (2024) 71 doi: 10.36922/ijb.2311

