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International Journal of Bioprinting                                3D bioprinting of nerve guidance conduits




            best performance in facilitating directed axonal extension   PCL.  Ouyang et al.  developed a seamless axial NGC
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            and SC migration in vitro due to the combined effects of the   consisting of biocomposite collagen/PLGA nanofibers by
            topological cues provided by the aligned nanofibers and   electrospinning  and  evaluated  the  ability  of  the  conduit
            the biochemical cues retained in the porcine decellularized   to support SC proliferation and axonal growth both  in
            nerve matrix hydrogel. Consistent results were obtained in   vitro  and  in vivo. The aligned NSCs were significantly
            animal experiments with the fabricated NGCs, confirming   superior to those composed of randomly aligned collagen/
            that PLA is generally a promising approach for NTE and   PLGA fibers in facilitating regeneration and functional
            the treatment and diagnosis of PNI.                restoration and were nearly as effective as autologous grafts.
                                                               Moreover, the collagen/PLGA conduits were mechanically
            3.2.2. Polycaprolactone                            strong enough to suture severed nerve endings and resist
            PCL is a biodegradable aliphatic polyester characterized by   collapse in vivo, remaining structurally intact for at least
            a low melting point, ease of processing, high mechanical   3 months postoperatively. Namhongsa et al.  deposited
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            strength, good biodegradability, and miscibility with   polypyridine particles on 3D-printed poly(l-lactic acid-
            various  other  polymers.   However,  due to its  high   co-ε-caprolactone)/PLGA conduits to change the electrical
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            plasticity,  the  physical,  chemical,  mechanical,  and   conductivity of the conduit  surface. Studies  have shown
            biological properties of PCL can be improved by modifying   that PLGA-based conduits degrade faster and are more
            functional groups or combining it with other materials   suitable for short-gap nerve injuries, and vice versa. By
            (e.g., synthetic polymers, metallic materials, etc.).  PCL-  optimizing the structural and surface modifications of the
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            based NGCs support the adhesion and proliferation of SCs   conduits, these materials can provide a favorable option
            and olfactory sheath cells without causing severe swelling   for enhancing cellular biocompatibility. The controlled
            that may locally compress the nerve. Zhu et al.  employed   degradation properties of PLGA are also a valuable factor
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            electrospinning techniques to fabricate a PCL-based NGC   for achieving multi-phase release of neurotrophic factors.
            featuring directionally aligned fibers complemented by a   For instance, Lackington et al.  developed a PLGA
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            concentration-gradient NGF coating on its surface. This   microparticle with encapsulated NGF and glial-derived
            innovative design facilitated the directional guidance of   neurotrophic factor. The factors are sequentially released
            DRG neurons toward the high NGF-concentrated region   into the nerve regeneration microenvironment over 28
            and successfully repaired a 15 mm sciatic nerve defect   days, promoting nerve repair. However, PLGA generally
            in rats. Chen et al.  tested the mechanical properties   exhibits poor hydrophilicity, and its degradation products
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            of 3D-printed PCL conduits with maximum tensile    create an acidic microenvironment, often resulting in
            strength and modulus of elasticity of 21.2 and 142.5 MPa,   limited bioactivity.
            respectively—values significantly higher than those of
            native nerves. This enhanced strength offers greater ease   3.2.4. Polyethylene glycol
            of handling and suturing during surgical procedures. Qian    PEG is a linear polyether compound with strong mechanical
            et al.  innovatively invented an LBL casting method   and degradation properties that can encapsulate cells, good
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            for the fabrication of NGCs, utilizing either single-layer   hydrophilicity, and water absorption. However, due to its
            graphene  or  multi-layer graphene  with PCL.  Results   biological inertness and poor oxidative stability, it may
            showed that the higher the number of layers of graphene,   cause cell death during ultraviolet cross-linking. Therefore,
            the lower the conductivity achieved (8.92 × 10  S/cm for   it is typically combined with other biomaterials to improve
                                                 −3
            a single-layer graphene/PCL conduit, 6.37 × 10  S/cm   its performance.
                                                    −3
            for a multi-layer graphene/PCL conduit). All the above-           114
            mentioned studies demonstrate that NGCs made from     Berkovitch et al.  sought to evaluate hydrogel assemblies
            PCL have great potential for future research and clinical   PEG-fibrinogen (Fib) in different formulations for NGCs.
            applications.  In  addition  to  this,  even  with  synthetic   Three PEG-Fib hydrogels were prepared and tested:
            polymers, hybridization with other materials is still an   compliant PEG-Fib, rigid PEG-Fib, and micropatterned
            essential way to enhance the performance of conduits.  PEG-Fib with microchannels. All three compositions were
                                                               implanted into 8 and 12 mm rat sciatic nerve defect models
            3.2.3. Poly(lactic-co-glycolic acid)               to verify their effectiveness in repairing PNI. Rigid PEG-
            PLGA is a functional polymeric organic compound formed   Fib constructs containing 40 mg/mL of PEG diacrylate
            by the random polymerization of two monomers, lactic acid   (PEGDA) were shown to be better at promoting complete
            and hydroxyacetic acid, with a controlled biodegradation   bridging at the injury site compared to fibronectin/
            rate  and good cell adhesion. Although the degradation   PEGDA. The semi-synthetic compositions were superior
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            rate of PLGA reduces with increasing lactic acid content,   to fibronectin and fibronectin/PE-DA in bridging nerve
            it remains significantly higher than that of PLA and   injuries. In addition, PEG conduits promoted homeostasis


            Volume 11 Issue 4 (2025)                        46                            doi: 10.36922/IJB025140120
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