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International Journal of Bioprinting                                  3D printing technology in neurotrauma




            and found that it was beneficial to the growth of motor   FDM method into the adult zebrafish TBI model, the
            neuron axons. 104                                  neurological function of the zebrafish was restored.

            3.1.2. Synthetic biomaterials                      3.1.3. Composite biomaterials
            Synthetic biomaterials have better physical properties and   Natural  biomaterials and  synthetic biomaterials  can  be
            controllable degradation rates than natural biomaterials   further compounded for 3D printing to treat neurotrauma.
            and have been used in many fields of biomedicine.    Composite biomaterials refer to biomaterials composed
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            Synthetic biocompatible polymers such as PCL, poly   of two or more materials with different physicochemical
            lactic acid (PLA), poly-L-lactic acid (PLLA), and poly   properties.  For example, various materials can combine
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            lactic-co-glycolic acid (PLGA) have diverse chemical   with natural biomaterials to form composite biomaterials,
            properties, controllable degradation rate, and high-water   such as microspheres, conductive polymers, and
            absorption. 106,107  Various synthetic biomaterials have been   electrospun fibers.  Wei et al. synthesized GelMA and
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            adopted for 3D printing of nervous system injury repair.   graphene  nanoplatelets  into  composite  biomaterials  and
            Kaplan et al. produced polyester scaffolds composed of   made them into 3D scaffolds through the SLA method.
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            PLGA and PLLA for nerve tissue regeneration based on   In vitro experiments have confirmed that this scaffold
            3D printing.  This customized scaffold closely simulates   benefits the survival and differentiation of NSCs and the
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            the morphology of neural tissue and is beneficial to the   repair  of  neural  tissue.   To develop biomaterials  with
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            survival and proliferation of iPSCs-derived neurons   biocompatibility and proper mechanical strength for PNI,
            and axon regeneration. Besides, Qian et al. developed   Wu  et  al.  developed  composite  hydrogels  by  combining
            PCL conduit loading with GO nanoparticles through an   GelMA and SF-MA, in which GelMA is beneficial for cell
            extrusion method.  They found that the conduit exhibited   adhesion while SF-MA can provide mechanical strength.
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            uniform nanoparticle dispersion, porous structure, strong   They found that GelMA/SF-MA with a ratio of 1:1 was
            mechanical strength, and high electrical conductivity. They   optimal for Schwann cell behaviors including cell adhesion,
            also demonstrated that the PCL/GO scaffolds positively   proliferation, spreading, and migration. In addition, they
            affect the proliferation, adhesion, and functions of Schwann   also  designed  and  prepared  photopolymerizable  plasma
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            cells, and the conduits could promote angiogenesis and   by a mild one-pot method.  This composite biomaterial
            functional recovery of a 15 mm sciatic nerve defect.  In   derived from plasma contains various proteins and growth
            addition to the polyesters introduced above, there are   factors, and the formulation of the composite biomaterial
            many synthetic hydrogel constructs that have been used   is similar to that of physiological conditions. They found
            in neurotrauma, such as PEGDA and polyurethane (PU)   that the plasma hydrogel could sustainedly release growth
            hydrogels. PEGDA is modified with polyethylene glycol   factors and promote the neurite elongation of PC12 cells,
            (PEG) terminal hydroxyl groups, and polyethylene glycol   which is promising for fabricating personalized nerve
            dimethacrylate (PEGDMA) is also formed similarly. They   guide conduits for PNI by DLP printing.
            form hydrogels through photo-crosslinking, making them
            suitable for 3D printing methods such as SLA and DLP.   3.2. Physical regulation
            For example, Pateman et al. produced PEGDA hydrogel   3.2.1. Light stimulation
            conduits, which promote the dorsal root ganglion to   The role of light stimulation after neurotrauma is to rebuild
            proliferate, differentiate, and orientate  in vitro and   lost neuronal circuits. In recent years, low-intensity light
            support  nerve  re-connection  in vivo.  Biodegradable   therapy  (LLLT)  has  gradually  become a  new  strategy  to
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            PU is an emerging synthetic biomaterial because of its   improve function through external stimulation of cells. 118,119
            biocompatibility, elasticity, mechanical properties, and   LLLT, also known as photo biomodulation, has been
            flexibility. 110,111  Polyurethane is a copolymer formed by   used to cure many clinical diseases, including promoting
            the polymerization of polyols, small-molecule chain   wound healing, reducing pain and inflammatory
            extenders, and isocyanates. Huang et al. synthesized a   responses, accelerating tissue recovery, and treating
            new biodegradable waterborne PU and mixed graphene   certain neurological diseases. 120,121  Although the precise
            with PU to produce a graphene-based composite bioink   biochemical mechanism of LLLT regulation remains to be
            for 3D bioprinting.  The rheological properties of the   elucidated, it has been shown that LLLT is implicated at the
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            bioink facilitate NSCs survival and printing. Hsieh et al.   molecular, cellular, and tissue levels.  Zhu et al. produced
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            prepared thermoresponsive water-based PU dispersions   a transparent scaffold consisting of GelMA and PEGDA
            and demonstrated that the NSCs had good proliferation   by  SLA,  which  could  combine  with  LLLT.   In  vitro
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            and differentiation capabilities in the dispersions.  After   experiments have proven that this 3D-printed scaffold,
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            implanting the scaffold made of this dispersion by the   combined with a light stimulation strategy, can promote


            Volume 10 Issue 3 (2024)                        72                                doi: 10.36922/ijb.2311
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