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International Journal of Bioprinting                                     Applications of 3D printing in aging



            physiological pressure of normal blood vessel. Lee et al. [147]    diseases. Cardiovascular structure restoration is made
            3D-printed biodegradable PLA stents using polymer   possible by the careful sorting and placement of cells or
            electrolyte  membrane  (PEM),  and  used  polydopamine   tissue blocks in a complex 3D microenvironment with
            (PDA), polyethyleneimine (PEI), and heparin (Hep)   bioprinting technology. Although bioprinting techniques,
            to prevent restenosis and thrombosis by improving   bioink materials, and post-bioprinting processing are still
            anticoagulation and hemocompatibility. Alonzo  et al. [148]    in their infancy in this area, reproducing heart structures
            3D-printed annular  hydrogel (gelatin-alginate) scaffolds   including the myocardium, blood arteries, and heart valves
            with microvascular endothelial cells using DIW. These   via 3D bioprinting has shown great promises. New bioinks
            3D heart-like scaffolds supported long-term cell survival,   and printers with the ability to manufacture objects with
            function, and maintenance of cell phenotype throughout   high resolution will advance the science and eventually
            the entire culture period because they were structurally   accomplish the ultimate goal of total organ engineering.
            and mechanically stable with highly interconnected pores.
            The model supported paracrine signaling in addition to   3.4. Digestive system
            heterogeneous cellular contact between endothelial cells   3.4.1. Application of 3D printing in oral cavity
            and cardiac fibroblasts, cardiomyocytes, and both [148] . Jia   diseases
            et al.  used a multilayer coaxial extrusion technique to   The tooth loss among the elderly people is mostly caused
                [19]
            3D-print a cell-responsive bioink made of GelMA, sodium   by periodontal and dental caries. While the gums are aging
            alginate, and 4-arm poly(ethylene glycol)-tetraacrylate   and shrinking, the exposed area of the cervical root is
            (PEGTA) to enable direct 3D bioprinting for one-step   increased, thereby elevating the risk for caries [150] . Aging also
            production of perfusable vascular systems with highly   causes severe resorption of alveolar bone, in which case, the
            organized  structures.  This  hybrid  bioink  encapsulated   supporting structure of teeth is destroyed, causing instability
            stem cell and endothelium in bioprinted structures and   in teeth. Long-term caries and periodontal diseases activate
            supported their growth, producing biologically relevant,   the oxidative damage by free radicals and weaken the
            highly structured, and perfusable vasculature. Lee et al. [149]      repairing ability of the oral cavity, causing tooth loss in the
            proposed free-form reversible encapsulation with   elderly. In summary, tooth loss in the elderly is a systemic
            suspended hydrogels (FRESH) to directly write collagen   process caused by many factors associated with aging [151-154] .
            into  bioconstructs  of  various  scales,  ranging  from
            capillaries to whole organs. At 20-µm filament resolution,   Tooth loss adversely affects the life quality and brings
            porous microstructures were capable of cellular infiltration   great harm  to the elderly  both  physically  and  mentally.
            and microvascularization. The mechanical strength   Dental regeneration faces a significant difficulty in
            adequate for the production and perfusion of multi-scale   replicating the structural complexity and multicellular
            vascular systems and trilobular valves were enabled via   interactions that  resemble their  natural 3D  counterpart.
            pH-driven gelation control. The results showed that the   Due to improvements in 3D printing technology, which
            3D-bioprinted heart accurately reproduced the patient-  enables the creation of structures with patient-specific
            specific anatomy determined by micro-CT (Figure 4D).   characteristics, efforts to construct teeth and dental support
            Human cardiomyocyte imprinting resulted in coordinated   devices, such as periodontal ligament, alveolar bone, and
            contraction, directed action potential propagation, and   dental ossicles, have made some progress [155,156] . Although
            wall thickening of up to 14% at peak contraction in the   some dental applications of 3D printing are not targeted at
            ventricular tissues.                               the aging population, we focus on the potential applications
                                                               of these cases in the elderly population, such as 3D-printed
               The application of 3D printing in cardiovascular diseases   crowns and dental implant scaffolds for dental implants in the
            mainly involves cardiovascular phantoms fabricated by   elderly. It is becoming more apparent that a single material
            material jetting, cardiovascular stents fabricated by material   is difficult to meet all the requirements; therefore, the search
            extrusion, and heart patches for treatment fabricated by   for more suitable hybrid materials has also become one of the
            material extrusion. Materials for bioink mainly include   focuses of tissue engineering development [157] . Jeong et al. [158]
            biopolymers such as GelMA and ECM. Live and functional   used PEM to 3D-print PCL mixed with HA/β-tricalcium
            cells are frequently encapsulated and printed together   phosphate (β-TCP) into novel scaffolds. It combined bone
            with the biopolymers to simulate certain functions of the   grafting and implant fixation devices to simplify alveolar
            cardiovascular system in vitro. However, 3D printing of the   bone regeneration and dental implant procedures. The
            entire organ remains difficult. Cardiovascular system is a   new scaffold had high porosity and good microstructural
            complex anatomical structure. Therefore, to replicate its   interoperability. Cell proliferation and alkaline phosphatase
            internal structure and reproduce its function is the greatest   assay results were significantly better than those of control
            challenge in the research and treatment of cardiovascular   scaffolds. The emergence of new hybrid materials is often


            Volume 9 Issue 4 (2023)                        246                         https://doi.org/10.18063/ijb.732
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