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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
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