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International Journal of Bioprinting                                dECM bioink for in vitro disease modeling




            nerve bundle, the CNSdECM can support neurons more   body.  The vascular conduits and contractile tissues are
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            as they grow and secret new ECMs, as opposed to Matrigel,   interconnected with high complexity and heterogeneity. The
            which is degradable and not able to maintain the structural   vascular network delivers oxygen, nutrients, metabolites,
            integrity. Moreover, 3D bioprinting-based models have the   and blood. Arteries transport oxygen-rich blood from the
            advantage of realizing the engineered design of the tissue   heart to other organs, whereas veins deliver metabolites
            analog, which is similar to the native tissue structure.   to organs and tissues such as kidney and liver. Capillaries
            Conventional methods are limited to building 2D    are  also  involved  in  substance  transport,  mediated  by
            structures and structures naturally generated from cellular   diffusion through thin endothelia. The heart acts as a
            differentiation. The 3D bioprinting structure in adherence   pump to induce blood flow. Thus, any disruptions to the
            with the engineer’s design, which is intended to enhance   structural integrity and functions of cardiovascular tissue
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            the physiological resemblance to native tissues, is feasible.   place an obstacle to substance circulation in the body.
            However, the current nervous system models require   One of the most prominent conditions associated with
            improvement with regard to precise control of neuronal   CVDs is atherosclerosis, which occurs as a result of plaque
            direction and maturation. The technical limitations can be   formation in the arterial walls due to high cholesterol and
            overcome by applying various 3D bioprinting methods and   triglyceride  levels.  The development of  atherosclerosis is
            incorporating nervous tissue-specific dECMs and specific   also closely related to the alterations in hemodynamics,
            components of the dECM. 85,148  For example, the BBB—a   which can be affected by changes in vascular geometry.
            brain-specific vascular structure—plays an essential role in   Numerous experimental cardiac tissue models are
            the CNS as an innate barrier with selective permeability   available  for  clarifying  the  mechanisms behind cardiac
            to prevent penetration of foreign material.  Owing to the   diseases. Generally constructed on Transwell inserts,
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            tightly impregnable layer of endothelial cells in the BBB,   traditional  in vitro 2D vessel models, which belong
            most drug molecules as well as pathological factors cannot   to the category of cardiac tissue models, allow for the
            penetrate into the neural tissue. Thus, it is necessary to   observation  of  material  penetration  from  one  side  to
            develop BBB-incorporated neural tissue models (i.e.,   other side in the endothelial layer.  These models have
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            neurovascular unit models), which can be utilized in   contributed to  our  understanding  of transport  through
            studies for deciphering the penetration mechanism, and   the  endothelium.  Additionally, 2D  cardiac  models have
            to identify a proper strategy for transporting drugs to the   been used to investigate cardiac myocyte behavior in
            brain. For this, a vascular structure can be added to the in   cellular models.  However, the limited geometry of the
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            vitro neural model via 3D bioprinting. 3D bioprinting has   models  constrains  their  usefulness  in  the  delineation  of
            potential for building various tubular structures for vessels   vascular and cardiac physiology, which are related to the
            and adapting different cell types for reconstructing complex   geometry and mechanical properties of cardiac tissue.
            organ systems. Thus, 3D-bioprinted neurovascular unit   Furthermore, the hemodynamic mechanism in vessels
            models, integrating the BBB and neural tissues, should   has not been sufficiently elucidated from the viewpoint of
            be constructed to aid elucidation of the crosstalk between   biomechanical-therapeutic interplay. Thus, the mimicking
            neural cells and BBB.                              potential of conventional microfluidic vascular models is
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               Furthermore, additional bioreaction can support   limited to the recapitulation of various vascular geometries,
            the  recapitulation  of  the  complex  structure  of  central   which is not feasible for clarifying CVD mechanism. To
            nervous tissue, such as the aligned neural network. The   overcome this limitation, recapitulation of 3D geometry
            directionally controlled neural network is important for   has attracted attention. For example, Gao et al. suggested
            elucidating neural signal transduction in the CNS. In   the use of vascular tissue-derived dECM (VdECM)-based
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            addition, 3D-bioprinted neural models incorporated with   arteries in atherosclerosis modeling (Figure 3C).  The
            electrical sensors and reactors, such as microelectrode   VdECM has shown favorable effects on the angiogenesis
            arrays, can widen the applicability of in vitro models in the   and proliferation of endothelial cells by supporting the
            context of healthy and pathological signal transduction in   expression of cell–ECM attachment factors (e.g., vascular
            the CNS. 151                                       endothelial [VE]-cadherin, integrin beta-1), as reported in
                                                               various studies. By capitalizing on these vascular-related
            4.2. Cardiovascular tissue-derived decellularized   advantages, Gao et al. developed a vessel structure using
            extracellular matrix                               triple coaxial printing with VdECM.  To simulate the
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            Cardiovascular disease (CVD) is a chronic and difficult-to-  heterogeneity of the arterial structure, smooth muscles cells
            cure illness with the highest mortality rate in the world. 152,153    (SMCs) and endothelial cells (ECs) were employed in the
            The cardiovascular system consists of the heart, arteries,   triple coaxial printing. The geometry of the three-layered
            veins, and capillaries that circulate blood throughout the   artery is adjustable; modifications can give rise to regular,


            Volume 10 Issue 2 (2024)                       145                                doi: 10.36922/ijb.1970
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