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International Journal of Bioprinting                                3D bioprinted vascularized tissue models





































            Figure 3. 3D bioprinting of vascularized kidney models. (A) Sacrificial bioprinting for creating a 3D convoluted renal proximal tubule model on customized
            perfusable chip [from ref.  licensed under Creative Commons Attribution 4.0 license]. (B) Sacrificial bioprinting for engineering a 3D vascularized proximal
                            [28]
            tubule model with co-localized vascular and proximal tubular channels  [from ref.  licensed under Creative Commons Attribution-NonCommercial-
                                                                 [53]
            NoDerivatives License 4.0 (CC BY-NC-ND)]. (C) Coaxial bioprinting of a perfusable in vitro multi-organ model resembling pathophysiological features
            of secondary hyperoxaluria. Reprinted from Yoon J, Singh NK, Jang J, et al., 2022, 3D bioprinted in vitro secondary hyperoxaluria model by mimicking
            intestinal-oxalate-malabsorption-related kidney stone disease. Appl Phys Rev, 9(4): 041408 , with the permission of AIP Publishing .
                                                                                               [55]
            model, which facilitated in the evaluation of an anti-  bloodstream,  and  these  functions significantly  rely on
            fibrogenic effect of drug combination.             the active interaction between renal tubules and vascular
                                                               networks. Most kidney models are based on micro-fluidic
               In sum, current liver in vitro models recapitulate the   chip devices that simulate fluid environment to support
            structural and functional features of hepatic lobules and   renal tubular cell growth and function [51,52] . However, their
            vascular networks to certain extent. Despite successful   anatomical structures, complexity, and functionality are
            attempts, challenges still remain in the fully reproducing   still lacking to fully model renal tissue. To recapitulate the
            the liver functions  in vitro through the 3D bioprinting   structural and functional complexity of the kidney, 3D
            of vascularized liver models. Owing to the natural   bioprinting provides an attractive strategy for developing
            heterogeneity of the liver composition and architecture,   kidney  in  vitro models with tube-like micro-fluidic
            the synchronous control of microenvironmental cues,   structures [28,53,54] . Homan et al.  developed a convoluted
                                                                                       [28]
            including signaling pathways, heterocellular organization,   renal PT model on perfusable chips (Figure 3A). The
            metabolism, ECM, and fluidics, for hepatic and vascular   sacrificial bioprinting approach was employed to prepare
            development is key to modeling a fully functional   a perfusable channel using fugitive sacrificial PF-127 and
            liver. Robust vascular systems with ample multi-scale   a gelatin-fibrin ECM hydrogel. After the removal of PF-
            vasculature also need to be addressed to ensure the long-  127, human proximal tubule epithelial cells (PTECs) were
            term investigation of bioprinted liver models.     introduced within the hollow channel to form a 3D tubule
                                                               with epithelial lining. Compared with PTEC 2D models,
            3.3. 3D bioprinting of vascularized kidney models  the perfusable 3D PT model exhibited the formation of a
            The kidney is responsible for the maintenance of body   tissue-like polarized epithelium with improved phenotypes
            fluids homeostasis and waste excretion functions.   and superior albumin uptake function. The mature
            Nephron is a complex functional unit of the kidney   epithelium was applied in testing nephrotoxicity with a
            with  the ability to filter  and reabsorb solutes  from the   known compound (i.e., cyclosporine A). Upon exposure,


            Volume 9 Issue 5 (2023)                         25                         https://doi.org/10.18063/ijb.748
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