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International Journal of Bioprinting                                dECM bioink for in vitro disease modeling




            bioreactor can be minimized, allowing for generation of   substitutes. 88,231   Nonetheless,  augmenting  dECM  bioink
            results that are highly reflective of the actual situation of   with other hydrogels is considered a reasonable strategy
            respiratory system.                                for improving the printability of the bioink through the
                                                               improvement of its physical properties, and there are
            5. Conclusions and future perspectives             attractive methods for accomplishing this integration. 232,233

            To create 3D structure and to simulate pathology-specific   For example, Ali et al. improved the physical properties of
            microenvironment in a disease model, it is important to   a bioink using a methacrylated-dECM bioink and applied
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            select appropriate biomaterials and model manufacturing   it to kidney regeneration,  whereas Kim et al. developed
            methods.  From this perspective, the combination   a light-activated dECM bioink and successfully fabricated
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            of dECM as a biomaterial and 3D bioprinting as a   centimeter-scale 233  structures  using  extrusion-based
            manufacturing method is currently a promising approach   3D bioprinting.  These methods, which leverage the
            to fabricate disease models.  First, 3D bioprinting can be   advantage of dECM bioink, can be used to fabricate stable
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            used to process various cells and biomaterials that constitute   3D structures to improve their mechanical properties while
            organs into shapes suitable for creating pathophysiological   maintaining their characteristics essential for creating
            structures.  3D bioprinting can create in vitro and in vivo   tissue-specific microenvironment.
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            models that precisely mimic the structures and functions of   To maximize the utilization of the enhanced dECM
            human organs via the spatial placement of cell-containing   bioink through the previously mentioned methods in
            bioink. To maximize  the advantages  of 3D bioprinting,   various applications, the versatility of 3D bioprinting
            it is important to select an appropriate biomaterial that   technology itself is essential. To develop more diverse
            can create the microenvironment of the disease model.    disease models and to fabricate large-volume structures
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            Therefore, employing dECM as a bioink to reproduce the   for tissue regeneration, it is necessary to improve
            ECM composition specific to a given organ has considerable   fabrication technology, in terms of fabrication time and
            potential  for  simulating  the  pathophysiological  precision, using advanced dispensers and nozzles.  These
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            microenvironment of a disease.  3D-bioprinted disease   requirements can be fulfilled by adopting a combination
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            models created with dECM bioinks have demonstrated the   of existing 3D bioprinting technologies.  For example,
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            potential for pathophysiological mechanism studies, tissue   Brassard  et  al.  successfully  generated  macroscale
            regeneration, and drug screening for various diseases.    tissue blocks using a combination of extrusion-based
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            However, widespread application of 3D bioprinting using   and inkjet bioprinting techniques.  Moreover, it is
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            dECM bioinks is limited by several challenges.  Some of   difficult to accurately control the printing conditions
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            these challenges associated with dECM and 3D bioprinting   of a conventional 3D bioprinting system in real time,
            for the fabrication of various disease models are discussed   such as temperature and humidity, setting the stage for
            as follows. Approaches to overcome these problems are   problems in the precision of structure manufacturing
            also proposed. Additionally, ethical and legal issues related   using dECM.  Therefore, it is necessary to establish a
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            to 3D bioprinting and dECM bioink are briefly addressed.  printability database for dECM bioinks and to apply real-
                                                               time automatic control to printing systems.
               Biomaterials suitable for 3D bioprinting must possess
            specific physical properties to ensure mechanical stability of   Other  challenges related  to dECM  bioinks  include
            the printed structure. In the case of hydrogels, for example,   reproducibility and standardization issues.  The toxicity
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            their  restricted crosslinking  limits  their applicability  as   of agents used for decellularization and incomplete cell
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            bioinks.  Therefore, to have a high degree of freedom in 3D   removal have also emerged as additional problems.  The
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            bioprinting, it is necessary to develop advanced biomaterials   dECM is an attractive biomaterial for tissue regeneration
            with controllable physical properties through the chemical   and disease models because it can be used to create tissue-
            or physical treatment of conventional biomaterials.   specific microenvironments.  However, the dECM
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            Regarding dECM,  its  important property  is  that it  can   composition changes slightly from batch to batch, resulting
            simulate an organ-specific microenvironment.  However,   in functional differences.  To address this problem,
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            despite their biochemical superiority, dECM bioinks have   standardization of the material preparation process is
            insufficient mechanical properties to fabricate various   required.  There  is  a  method  for  decellularizing  large
                                     15
            structures with high resolution.  One possible supportive   amounts of tissue to produce large amounts of dECM at
            method that addresses this limitation is the integration   once and mixing it.  A thorough analysis of all components
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            of a hydrogel with a polymer, such as polycaprolactone   of each organ-derived dECM lays a foundation for the
            (PCL) and polyethylene-vinyl acetate (PEVA), to enhance   quantitative standardization of their composition, which is
            structural integrity; however, plastic scaffolds may limit   instrumental for the creation of a more potent and uniform
            the usage of printed analogs in the context of native tissue   biological material. Furthermore, animal-derived dECM

            Volume 10 Issue 2 (2024)                       151                                doi: 10.36922/ijb.1970
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