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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
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