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International Journal of Bioprinting                              Bioprinted tissue-on-a-chip in drug screening




            hepatocytes and gelatin containing human umbilical vein   the crosstalk between epithelium and endothelium. The
            endothelial  cells  (HUVECs)  were  printed  at  the  bottom   administration and subsequent withdrawal of dapagliflozin
            of the channel, accomplishing the one-step construction   reduced and restored the rate at which glucose was
            without additional bonding and adhesion (Figure 6A). In   reabsorbed in the kidney tubule model. In addition,
            this study, 3D bioprinting is employed in the fabrication   the state of the constructed model could be regulated
            of the whole tissue model, including microfluidic channels   through applying different perfusable materials. In the
            and tissue-culture chambers, which allowed higher liver   hyperglycemic state, this model with notable changes in
            activity than static culture. Furthermore, the biliary system   cell morphology and drug effects offered a solid basis for
            excreting the bile acids that were toxic to the hepatocytes   further pathological and drug research.
            was incorporated into the novel model developed by Lee    Park et al.  utilized PCL to assemble three communicating
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            et  al.,   which  contained  two  chambers  separated  by   chambers,  containing bioink with endothelial cells as
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            a porous membrane. The upper chamber supported     the  central  chamber  and  the  bioink  with  pulmonary
            culture cells and was perfused by fluids while metabolic
            waste leaked into the bottom chamber. The expression   fibrocytes as chambers on both sides. The two chambers
            of specific proteins to biliary duct demonstrated the   were separated from the central chamber to ensure media
            successful construction of liver model with the biliary   flow.  The capillary network was  generated  in  the  central
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            duct. The physiological and structural characteristics of   chamber. Marino et al.  fabricated blood–brain barrier-
                                                               on-a-chip (BBB-on-a-chip) with two-photolithography.
            hepatobiliary  interdependence  were  embodied  in  the
            model. This dual-channel system embodying two-organ   The bioprinted vessels with well-distributed micropores
            features also provided the potential for integration into   were arranged in parallel, mimicking the microcapillaries in
            multi-organ chips.                                 BBB for brain tumor and lesions research. Similarly, Mandt
                                                               et al.  designed the x-shaped microfluidic chamber with
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               Heart tissues, with structural complexity and   wave-shaped  condensates  and  printed  it  on  the  interface
            physiological importance, attract significant interest   via  two-photolithography.  It  reproduced  the  placental
            from many investigators. Zhang et al.  utilized coaxial   barrier to investigate the permeability of glucose molecules
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            bioprinting with nozzles that are designed in a concentric   (Figure 6B).
            circle shape. The inner nozzle was filled with a crosslinked
            solution, and a blend of GelMA and alginate was printed in   Pulmonary alveoli directly exposed to the environment
            the outer nozzle as shells. This structure that was printed   are used for gas exchange between inhaled air and blood.
            on PDMS carried myocardial endothelial cells, which   The epithelium and the endothelium in blood–air barrier
            were guided into the bioprinted filament surface to form   are  located on  each  side  of  the  basement  membrane.
            a tubular cavity. A cardiomyocyte suspension was then   This micron-thick structure with three-layered cells was
            perfused for cell inoculation in this construct. The resulting   constructed by drop-on-demand piezoelectric bioprinting.
            endothelialized cardiac model facilitated cell growth aligned   The printer with multi-jet nozzles was utilized to fabricate
            along the long axis to replicate the cardiomyocyte bundle   mold containing four cylinders for supporting tissue-
            architecture in vivo. The drug azithromycin exhibited dose-  embedded inserts. The upper layer of the 3D structure was
            dependent effects and significantly reduced the beat rate   obtained by casting the PDMS into the printed mold and
            of cardiomyocytes, indicating the reliable potential of the   then assembled with a flattened PDMS layer. Subsequently,
            cardiac model for drug screening. Nevertheless, it should   the inserts were transplanted into cylindrical holes of
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            be noted that this model, which could be perfused, has no   the PDMS model (Figure 6C).  The chip was able to
            hollow tubular structures.                         replicate physiological microenvironments to investigate
                                                               influenza viruses and respiratory diseases. Furthermore,
               Proximal renal tubules, the chief reabsorbing structures,   this chip with flexible insert could conveniently integrate
            reabsorb most glucose and protein back into the blood. Lin   cultured cells from various organs. These chip models
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            et al.  introduced vasculature into renal tubules in their   would be composed of repeated building blocks with high
            model, which  was  used  to study  the  crosstalk  between   uniformity and resolution.
            epithelium and endothelium. Original sacrificial ink added
            with high-molecular-weight poly (ethylene oxide) (PEO)   4.2. 3D-bioprinted disease-on-a-chip
            was printed between the two modified ECM casting layers.   The OOCs and disease-on-a-chip (DOCs) are distinguished
            The vascular templates were removed at a low temperature,   by cell sources, and the latter accommodates lesion cells
            and then the cultured cells were inoculated by perfusion. At   instead of organ cells. DOCs allow for the reconstruction of
            the junction of the two tubes, the adhesion and increased   TME or lesion organs in the laboratory setting.  The liver
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            expression of transport proteins were observed, indicating   disease model was further developed based on previous


            Volume 10 Issue 3 (2024)                       186                                doi: 10.36922/ijb.1951
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