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International Journal of Bioprinting                                     Applications of 3D printing in aging



            or healthcare applications. Next, health conditions that   deposition with a focused thermal energy source (e.g., laser
            are associated with aging are closely examined according   or plasma arc). This process is now only used for metals.
            to  human  body  systems  with  a  strong  focus  on  the   Currently, the 3D printing methods that are commonly
            applications of 3D printing in these areas, including the   used in the biomedical field include material extrusion,
            creation of in vitro models, synthesis of therapeutics, and   vat photopolymerization, and material jetting, which are
            fabrication of rehabilitation and assistive devices (Figure 1).    described in detail in Table 1.
            Although 3D printing may not be directly used for
            addressing the aging issues of these human systems, it   3. Applications of 3D printing in medical
            is used to improve conditions in these systems that are   conditions associated with aging
            associated with aging. This review also includes some
            applications for general tissue engineering, but applicable   3.1. Nervous system
            for  addressing  human  aging  problems.  Some  of  the  3D   By 2040, the World Health Organization (WHO) forecast
            printing applications are not exclusively for aging-related   that due to the aging of the population, neurodevelopmental
            conditions, but also used for other purposes. In the end,   disorder (NDD) will overtake cancer as the second most
                                                                                [53]
            the opportunities, challenges, and prospects of 3D printing   deadly human disease . Aging is an important risk factor
            in the field of aging are discussed.               for NDD, such as Alzheimer’s disease (AD), Parkinson’s
                                                               disease (PD), amyotrophic lateral sclerosis (ALS), and
                                                               Huntington’s disease (HD). Frustratingly, almost all these
            2. 3D printing methods commonly                    diseases have no effective cures available today. Studies
            used in aging                                      show that the incidence of AD, PD, and ALS is significantly

            In 2009, ASTM International Technical Committee F42   positively correlated with age [54-57] . Aging causes multiple
            on AM classified AM (which is used interchangeably   unfavorable changes in the organism, which lead to a
            with 3D printing in this article) into seven processes,   progressive loss of synapses and inflammatory response in
                                                                                                      [3]
            including material extrusion, material jetting, binder   the nervous system, and finally to neuronal death . These
            jetting, vat photopolymerization, sheet lamination, powder   phenomena are observed in cells of neural tissues where
            bed fusion, and directed energy deposition . Material   degenerative lesions occur, but the sequence and intensity
                                                [24]
            extrusion is a method in which the ink is extruded from   of their occurrence vary.
            a nozzle and selectively deposited according to the desired   3.1.1. Alzheimer’s disease
            pattern. Compared with other 3D printing methods, it has   According to the latest statistics released by the Alzheimer’s
            the advantages of low printing cost, broad applicability to   Association  International,  by 2030,  75  million people
            many material systems, simple and convenient operation,   are anticipated to have dementia globally . The clinical
                                                                                                 [58]
            and fast printing speed. One of the more precise 3D printing   manifestations of AD are mainly cognitive dysfunction
            methods is material jetting, which prints by ejecting liquid   and memory impairment, and the main pathological
            droplets into desired patterns that are subsequently cured   features are the formation of senile plaques by extracellular
            by UV or other means. Vat photopolymerization is an   β-like amyloid deposition in the brain and intracellular tau
            AM method that uses photo-activated polymerization to   protein  hyperphosphorylation,  leading  to  the  formation
            selectively cure liquid photopolymer in a vat layer by layer   of intracellular fiber. There are many hypotheses about
            into 3D structures. It has the benefits of high processing   the pathogenesis of AD, such as amyloid β protein (Aβ)
            accuracy and smooth surface. Binder jetting creates 3D   toxicity, tau protein hyperphosphorylation, cholinergic
            structures by spraying adhesive onto a powder bed to   nervous system damage, gene mutation, vascular
            selectively bind powder materials into desired 3D structures.   factors, oxidative  stress,  neuroinflammatory  response,
            Postprocessing is often required to permanently set the   mitochondrial dysfunction,  autophagy disorder,  insulin
            shape of printed parts. The principle of sheet lamination is   signaling abnormalities, and intestinal flora imbalance [59-64] .
            that the material sheets are cut by laser, and then bonded
            or welded together to form a solid block. Sheet lamination   3.1.2. Parkinson’s disease
            printing technology is available in materials other than   After AD, PD is the second most prevalent
                                                                                    [65]
            sheet metal and even in almost any other material that can   neurodegenerative disease . As a result of the inability
            be curled, such as paper. Powder bed fusion does not use   to modulate motor activities, PD is characterized by
            adhesives to bind the powders together. Instead, a high-  resting  tremor, motor  bradykinesia,  stiffness,  and other
            energy beam, such as a laser beam or electron beam, is   symptoms that compromise the quality of life and finally
            directly imparted on the power bed to selectively sinter   result in severe disability. PD is primarily due to the loss of
            or melt powder primers into solid parts layer by layer. In   nigrostriatal dopaminergic neuron, resulting in a significant
            the directed energy deposition, the material melts during   decline in the dopamine levels in the striatum. Studies

            Volume 9 Issue 4 (2023)                        235                         https://doi.org/10.18063/ijb.732
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