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International Journal of Bioprinting                                3D bioprinting of nerve guidance conduits




            ± 31.6%; p < 0.01).  The degradation rate of the conduit   a guiding effect and bridged a 15 mm peripheral nerve
            was significantly reduced, and the structural stability was   defect in rats; myelinated nerve regeneration was observed
            enhanced. Zhang et al.  utilized chitosan/neurotrophic   at 8 weeks postoperatively, showing good nerve repair.
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            factor-3 for the 3D-printed topology micron track conduit   Yoo et al.  successfully 3D-printed a natural, unmodified
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            to induce targeted growth of SCs, showing a higher growth   collagen nerve conduit using a dense collagen solution
            density of primary SCs on micron track conduit compared   and implanted it into a rat nerve model. 6 weeks after
            to commercial conduits, which effectively facilitated the   implantation, the 3D-printed NGC showed a denser
            functional recovery of a 15 mm gap nerve injury model   and more organized pattern of regenerating axons.
            in rats.                                           Morphometric analysis of nerve sections distal to the
                                                               repair site at 12 weeks showed that myelinated axon counts
            3.1.2. Silk fibroin                                and myelin thickness were higher in the 3D-printed group
            SF is obtained from silkworm silk, which is a rich   than in the control group, confirming the beneficial effects
            natural source of proteins with outstanding mechanical   of 3D-printed collagen on axonal regeneration, myelin
            properties,  biodegradability,  biocompatibility,  and  sheath regeneration, and nerve cells’ functional recovery.
            bioabsorbability. 77–79  Silk can be processed in the form of   However, the main drawbacks of collagen are its high
            films, gels, nets, etc., having a wide range of applications in   cost, poor mechanical properties, and limited stability, as
            NTE, especially using electrospinning. For instance, both   it can only remain liquid at low temperatures. To address
            Dinis et al.  and Zhao et al.  electrospun SF-based 3D   this limitation, cross-linking or combining collagen with
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            NGCs. SF-NGCs had an ultimate peak stress of 4.0±0.6 MPa   synthetic materials is often necessary. For instance, Chen
            and a corresponding elongation at failure of 156.8±46.7%,   et al.  fabricated porous 3D-printed collagen/SF (C/S)
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            demonstrating that the SF-NGCs exhibited a mechanical   conduits adsorbed with secretome (ST) derived from
            behavior comparable to that of rat sciatic nerve, good   human umbilical mesenchymal stem cells (3D-C/S+ST).
            clinical application performance, and potential to promote   After co-culture with NSC, 3D-C/S+ST showed good
            nerve regeneration and functional recovery. Wang et al.    cytocompatibility, and infrared spectroscopy data showed
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            combined  electrostatic  spinning,  braiding,  and  coating   that 3D-C/S+ST had appropriate lipid-soluble and water-
            techniques to prepare a composite sericin protein NGC,   soluble chemical bonds suitable for neuronal cell adhesion
            which was implanted into a 10 mm nerve defect in rats.   and growth. From X-ray diffraction analysis, 3D-C/S+ST
            There was  no obvious inflammatory  reaction  after  8   also showed a desirable crystallinity, hence better control
            weeks of implantation. Apparent axonal and myelin tissue   of the rate of degradation. Therefore, the development
            appeared inside the conduit group at 12 weeks and directly   of collagen-based composites for NGC fabrication is a
            throughout the conduit tissue, indicating successful   common procedure to be considered.
            regeneration of the rat sciatic nerve within the conduit.
            Alternatively, Zhao et al.  prepared composite polypyrrole   3.1.4. Gelatin methacrylate
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            (PPy)/SF conduits cultured with SCs by combining 3D   Gelatin is a natural polymer derived from collagen  and
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            bioprinting with electrospinning. The results showed that   has excellent biocompatibility, hemostatic properties, low
            SCs mainly adhered to the surface of the conduits and   cytotoxicity, and antigenicity, and promotes cell attachment
            maintained normal morphology (full, pike-shaped, and   and growth.  However, its  mechanical  properties  and
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            shiny), good interconnection, and good proliferation. This   antimicrobial activity are relatively poor, with a tensile
            indicated that  the  composite PPy/SF conduit  promoted   strength that is generally 0.05–0.5 MPa. 89,90  Therefore,
            SC adhesion, differentiation, and proliferation. However,   it often needs to be crosslinked with other polymers
            obtaining SF is a complex and expensive process that   to promote its mechanical performance.  GelMA is a
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            demands specialized methods and resources. Moreover,   gelatin-based biomaterial chemically modified to promote
            variations in silk sources and processing parameters can   cell adhesion, growth, and degradation. GelMA has better
            affect the material’s quality and consistency.     mechanical tunability and structural stability than ordinary
                                                               gelatin. Its mechanical strength and degradation rate are
            3.1.3. Collagen
            Collagen is the most abundant protein in mammals, with   dependent on many factors, such as gelatin concentration,
            good biocompatibility, high stability, and the capability to   degree of methacrylation, and photo-crosslinking.
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            promote  axonal  regeneration  and  myelination.  Collagen   Gong et al.  proposed a hollow porous GelMA/
            types I and II are the key components of peripheral nerves.   Engelbreth–Holm–Swarm (EHS) NGC with 89.8%
            Several studies explored collagen and its derivatives as the   porosity, 167.6 μm pore diameter, 0.489 kPa tensile
            main material for the biofabrication of NGC. For instance,   modulus, and 0.314 kPa compressive modulus. 16 weeks
            Fujimaki et al.  developed a collagen-based NGC with   after implantation in rats, hematoxylin and eosin staining
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            Volume 11 Issue 4 (2025)                        44                            doi: 10.36922/IJB025140120
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