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International Journal of Bioprinting                                dECM bioink for in vitro disease modeling




            ECM composition exhibits tissue specificity.  The dECM   2.2.1. Extracellular matrix in central nervous system
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            provides a tissue-specific microenvironment containing   The nervous system is a sophisticated network of neurons
            various receptors and growth factors.  Moreover, tissue-  and glia cells.  ECM is an important constituent of the
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                                          15
            specific dECMs directly transmit special chemical signals,   network,  accounting  for 10–20%  of  the  volume of  the
            such as cytokines and growth factors, to surrounding   nervous system. For the central nervous system (CNS),
            cells, inducing cell growth and tissue-specific cellular   the main components are the basement membrane
            responses. 38                                      and perineural nets, including the neural interstitial
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               The differences in properties between the dECMs   matrix.  The basement membrane is a thin membrane
            of different organs affect the spatial distribution of   and an interface that separates astrocytic attachment
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            cell  surface  receptors  that regulate  cell morphology   and perivascular mesenchymal tissue.  It provides a
            and behavior.  Furthermore, dECMs regulate organ-  barrier,  which  is  called  the  blood–brain  barrier  (BBB),
                       39
            specific cell proliferation, migration, and behavior by   setting apart the neural tissues and the vascular structure
            participating in tissue polarization and transmission of   to protect the neural tissue from external pathogen.
            mechanical forces, and serve as a structural support for   In  addition,  the  basement  membrane  is  essential  for
            cells.  Additionally, specific components of the dECM   neural cell attachment and differentiation during the
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            are involved in organ development and maturation.  For   developmental process. The basement membrane
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            example, laminin promotes cell adhesion and migration,   consists of laminin, nidogen, collagens, fibronectin,
            and  fibronectin  is  essential  for heart, lung, and  kidney   and glycans, which are essential for the maintenance of
            formation and maturation. 41,42  The tissue specificity of the   barrier integrity. The perineuronal net is composed of
            dECM can be applied to 3D-bioprinted organ mimicry   various chondroitin sulfate proteoglycans (CSPGs), such
            and development of disease models that recapitulate actual   as neurocan, veriscan, brevican, and aggrecan,  which
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            pathophysiology.  The pathological dysfunction in ECM   primarily regulate neural plasticity of the perineuronal
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            induces disorder in various tissues, such as brain, liver,   nets. For example, CSPGs in the nets regulate excitatory
            and lung. Here, we briefly review the ECM composition   and inhibitory signal balance. Among these CSPGs,
            in  the  tissues  of  central  nervous  system,  cardiac  tissues,   brevicans interact with tenascin-R and regulate synaptic
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            liver tissues, and tissues of respiratory system, as well as   plasticity.   Another  feature  of  the  CNS  is  the  neural
            the role of ECM proteins. The main tissue-specific ECM   interstitial matrix, which is located between neurons and
            compositions are summarized in Table 1.            glial cells. 49



            Table 1. Main composition and role of tissue-specific extracellular matrix
             Tissue         Main components of ECM  Role of each ECM
             Central nervous   Laminin/Nidogen     Basement membrane, neural cell attachment, regulation of neural differentiation
             system         Fibronectin            Perineuronal nets, structural support, oligodendrocyte differentiation
                            Type IV collagen       Perineuronal nets, structural support, neural cell migration support
                            CSPGs                  Perineuronal nets, regulation of signal balance between excitatory and inhibitory signals
             Cardiac tissue  Fibronectin           Regulation of cardiac cellular polarity
                            Type IV collagen       Mechanical support to cardiac cells
                            Proteoglycans          Regulation of cardiac cellular differentiation
             Liver          Types I and III collagen  Maintenance of structure
                            Fibrillin              Regulation of elasticity and flexibility
                            Hyaluronic acid        Filling gaps in tissue
                            Proteoglycans          Regulation of gas exchange between cells
             Respiratory system  Types I, III, and IV collagen  Maintenance of organelle formation
                            Glycosaminoglycans     Responsible for gas exchange
                            Hyaluronic acid        Filling gaps in tissue
                            Proteoglycans          Formation of gel state in tissue
                            Elastin                Providing elasticity and flexibility
            Abbreviations: CSPGs, chondroitin sulfate proteoglycans; ECM, extracellular matrix.


            Volume 10 Issue 2 (2024)                       135                                doi: 10.36922/ijb.1970
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