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International Journal of Bioprinting 3D printing technology in neurotrauma

tumor, anti-fibrotic, and anti-inflammatory effects. Song et self-adhesive bandage made up of a grating inner layer
al. precisely prepared PCL scaffolds similar to spinal cord and a lamellar outer layer by DLP printing. Through click
shape by NFES technology, and loaded the ECM of rat reaction, the two layers can adhere to each other to form
spinal cord and OMT into hydrogel onto 3D scaffolds. a tube-like scaffold that could wrap the injured nerve sites.
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This scaffold exerts the anti-inflammatory and anti- The XMU-MP-1 nanoparticles were loaded in the grating
fibrotic effects of OMT, alleviates secondary SCI and glial layer, and the drug could be directionally released to the
scar formation, promotes axonal growth at the injured injured sites to promote functional recovery. 146
site, and improves the motor score of SCI rats. Certain
small-molecule cytokines can also be combined with 3D 3.3.2. Neurotrophic factors
bioprinting to treat CNS injuries. Stromal cell-derived Neurotrophic factors can promote the regeneration of
factor-1 (SDF-1), also known as chemokine CXCL12, is nerve fibers and synapses, and has been used to treat
a small-molecule cytokine belonging to the chemokine neurotrauma for better neurological recovery. There
protein family. It has been proven that SDF-1 recruits cells are many types of neurotrophic factors. For example,
to ischemic sites, reconstructs the regional blood supply, nerve growth factor (NGF) and its receptors are widely
and promotes the repair of ischemic injury. 138,139 Li et al. distributed in the nervous system. They have neurotrophic
used the DLP printing method to create a scaffold made of effects under physiological conditions and can promote the
hydrogel and SDF-1. The in vitro experiment showed that development and maturation of neurons. They also have
the SDF-1-loaded scaffold was beneficial to the survival neuroprotective effects under pathological conditions,
and proliferation of NSCs, and guided cell migration from protect neurons from damage, improve survival rate,
NSC spheroids inside microchannels. Some antibiotics and promote the regeneration and functional recovery of
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with crosslinking properties can also be used to treat CNS damaged neurons. For another example, brain-derived
damage. Genipin was shown to reduce sepsis and have neurotrophic factor (BDNF) and its receptors are widely
crosslinking properties, and therefore, was proposed to be expressed in the nervous system and act through the high-
a potential therapeutic agent for TBI. Based on this, Da affinity receptor tyrosine-protein kinase B (TrkB). BDNF
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et al. provided a protein-based interpenetrating polymer has a neuroprotective effect on a variety of neurons after
network (IPN) scaffold encapsulated with genipin for injury. This effect can extend to the cortical motor system
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treating TBI. 142 and increase the survival rate of motor neurons. Liu et al.
applied a low-temperature extrusion 3D printer to create
In terms of PNI treatment, small-molecule drugs a collagen/chitosan scaffold encapsulated with BDNF.
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have been combined with nerve guide conduit to realize In vivo experiments showed that a 3D printing scaffold
local drug delivery and conduit functionalization. combined with BDNF promoted nerve fiber regeneration,
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For example, 7,8-DHF prodrug nanoassemblies were reduced the cavity area of the injured site, and promoted
developed and encapsulated into a nerve guide conduit the recovery of motor function. Lee et al. produced a
by a DLP technology. It was found that the prodrug collagen and VEGF-releasing fibrin hydrogel scaffold by
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nanoassemblies with high drug-loading capacities within freeform fabrication (FF) technique. Subsequent in vitro
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the conduit could sustainably release the 7,8-DHF to experiments confirmed that the VEGF-loading scaffold
promote neurite elongation. Meanwhile, 3D-printed supported sustained release of the GF, and the C17.2
PCL NGCs with melatonin have also been demonstrated cells in the scaffold showed high viability. Meanwhile,
to promote Schwann cell proliferation and upregulate neurotrophic growth factors have also been introduced
neural-specific gene expression. 143,144 In addition, several into conduits to provide a beneficial microenvironment to
small-molecule drugs have also been proven to have the improve peripheral nerve regeneration after PNI. Notably,
potential to improve the functional recovery of injured Johnson et al. found that specific growth factor gradients
nerves. Tao et al. found that the Hippo pathway inhibitor and/or spatial distribution within conduits could guide
XMU-MP-1 could accelerate Schwann cell proliferation branch nerve regeneration for complex PNIs. It has also
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and migration and upregulate the gene expression of been reported that local delivery of multiple neurotrophic
neurotrophic factors. The XMU-MP-1-loaded conduits factors may display a better effect on nerve regeneration
fabricated by DLP printing exhibited improved efficacy than a single neurotrophic factor. In a recent study, Tao et
for nerve regeneration. Xu et al. also demonstrated that al. fabricated functional conduits by developing composite
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RGFP966 could promote Schwann cell remyelination bioinks of photopolymerizable polymers and platelets
through activating the PI3K-AKT-ERK signal pathway, isolated from whole blood. They found that the DLP-
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and the sustained RGFP966 release from the 3D-printed printed conduits could prolong the survival of the platelets
conduits could significantly promote functional recovery and sustainably release various neurotrophic factors. Thus,
after injury. In a recent study, Zhang et al. fabricated a the conduits provided a regenerative microenvironment
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Volume 10 Issue 3 (2024) 74 doi: 10.36922/ijb.2311