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International Journal of Bioprinting Applications of 3D printing in aging
neural differentiation and neuronal regeneration is an released from the 3D-printed scaffolds in a controlled
effective approach. Gu et al. constructed a 3D neural fashion for 2 weeks with good biocompatibility. Systems for
[79]
mini-tissue construct (nMTC) by 3D-printing human implanted drugs provide an alternative to treating chronic
neural stem cells (hNSCs) using DIW. hNSCs differentiated illnesses like neurodegenerative disorders. Renishaw used
into functional neurons in situ and supported glial cells selective laser melting (SLM) to assemble a 3D-printed
(Figure 2B). Zhou et al. fabricated gelatin methacryloyl titanium catheter into an internal drug delivery device
[80]
(GelMA)-dopamine(DA) hierarchical neural scaffolds that delivered cerebral dopamine neurotrophic factor
with NSCs using a customized stereolithography (SLA) 3D (CDNF) for the treatment of PD . Preliminary results
[84]
printer. The GelMA-DA scaffold had a 3D environment were encouraging, showing that the internal drug delivery
that was extremely porous and connected, which boosted device could be placed accurately with predictable efficacy.
the gene expression of the neuronal markers, namely TUJ1 This 3D-printed drug delivery device contributed to
and MAP2, supported NSC proliferation, and promoted improved efficacy and safety of CDNF, suggesting that
neural differentiation, which all point to the potential of future development of this technology would help alleviate
the scaffold for brain repair and regeneration. the distress of PD patients suffering from progressive
At the same time, 3D printing plays a huge role in neurological disease.
disease treatment due to its unique and personalized 3D printing also demonstrates important applications
structural customization. For instance, Dong et al. in assistive devices for aging care with neurological
[81]
prepared helical microcones of photocurable GelMA- disorders. In response to the tremor or trembling
based hydrogels by two-photon polymerization (2PP). symptoms of PD, Western University in Canada developed
Following that, composite multiferroic nanoparticles a 3D-printed wearable glove that suppressed tremors or
were added to the helices. The microcones therefore other muscle contractions caused by PD, allowing PD
displayed magnetoelectric characteristics (MENP) and patients to exhibit better motor control . Parizi et al.
[85]
[86]
became multifunctional soft helical microcones with 3D printed a smart ring called AuraRing, which tested the
high level of functional integration, capable of targeted onset of PD by tracking silent hand tremors. Diseases such
delivery of nerve cells, on-demand local wireless neuronal as ALS cause respiratory muscle weakness and require
electrical stimulation, and enzymatic digestion after a noninvasive ventilator with bi-level positive airway
delivery (Figure 2C). MENPs were incorporated into the pressure/continuous positive airway pressure (BiPAP/
microcones as part of a magnetic manipulation strategy, CPAP). Wu et al. used SLA technology combined with
[87]
acting as magnetically actuated components in low- MRI data to customize patient-specific masks for BiPAP/
amplitude rotating magnetic fields. The magnetic input, CPAP machines for muscle weakness caused by ALS,
which was also transformed to electrical output by these increasing patient comfort and reducing air leakage.
MENPs, were used to induce neuronal cell differentiation In general, the impact of aging on the nervous
under electrical stimulation. The microstructure provided system increases with age, and the onset of NDD greatly
a biocompatible matrix that supported the growth of cells affects the health and life of patients. 3D printing, with
and would degrade upon targeted neuronal cell delivery, its unique advantages, plays an irreplaceable role in the
which opens new avenue for targeted cell therapy for fundamental study and treatment of aging-related NDD,
trauma and disease of central nervous system .
[81]
from establishing more intuitive brain-like models for
3D printing also offers significant advantages in drug in-depth investigation of the pathogenesis of diseases, to
delivery and release for NDD. Pramipexole is used to targeted delivery and release of drugs through implantable
treat symptoms and signs of idiopathic PD in adults. The biological scaffolds, as well as to the manufacturing of
best working dose of pramipexole is patient-dependent. rehabilitation and assistive devices. Compared to traditional
However, only a limited selection of standard doses is cell models, tissue sections, and organoids, 3D printing is
available in the market. Gultekin et al. used fused able to print specific subtypes of neural cells and growth
[82]
deposition modeling (FDM) 3D printing to create dosage factors in region-specific arrangements to mimic natural
forms for pramipexole with varied release characteristics. tissue structures, which provides precisely choreographed
The results showed that 3D-printed tablets could be reconstruction of microscale neural networks and
successfully manufactured into personalized doses and connections with internal structures and physiological
that the desired drug release profile is achievable by features of the nervous system in a more 3D and more
adjusting the formulation (Figure 2D). Saylam et al. life-like manner, and hence a complete developmental
[83]
proposed the use of 3D-printed polylactic acid (PLA) and process of the nervous system. It also provides a method
chitosan (CS) neural tissue scaffolds loaded with levodopa for healing complicated nerve injuries, opening the door
for the treatment of PD and showed that levodopa was to the specialized care of several nerve injuries. In addition,
Volume 9 Issue 4 (2023) 238 https://doi.org/10.18063/ijb.732

