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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

