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




            factors and proteins, they cannot completely replicate   4.1. 3D-bioprinted organ-on-a-chip
            drug efficiency in the human body. However, these models   3D-bioprinted organ-on-a-chip (OOC), a complex but
            have the potential to substitute for animal models in the   more physiologically related model, is based on microfluidic
            preclinical screening phase for new drugs (Figure 5). Models   technology containing perfusable microfluidics, reaction
            with physiological or pathological organ characteristics   parts, and drug delivery channels. 3D-bioprinted OOCs,
            have been used for drug metabolism analysis and drug   as an advancement in the integration of 3D bioprinting
            toxicity evaluation.                               technology with microfluidic technology, are figurative
                                                               and momentous applications of hydrogel. When combined
               Disease models are  broadly  employed  in  different   with  bioprinting,  it  enables  the  printing  of  live  cells  in
            aspects of drug screening, such as comparing drug   functional hydrogel constructs that have similar spatial
            efficiency underlying different mechanisms and at varying   distributions to physiological microenvironments.  Since
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            concentrations, as well as studying drug-drug interactions   functional cells are bioprinted and perfused, the hydrogel
            and determining the feasibility of combined administration.  constructs could express specific factors and enzymes,

               In vitro models are superior to animal experiments that   possessing features of the mimicked microenvironments,
            are pretty limited due to ethical issues. The technologies   such as the oxygen gradient, acidity, abnormal vessels, and
            in 3D-bioprinted microfluidic models complement    dynamic perfusion. Once the cells have differentiated to be
            each other, enabling in vitro cultures to be cultivated   mature, drug solutions are applied for testing efficiency.
            and stimulated artificially in miniature form accurately.   Given their organ-like properties, OOCs are used
            3D-bioprinted microfluidic models have successfully   to explore drug toxicity for the organs by evaluating cell
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            eliminated the errors and time consumption associated with   viability, metabolic activity, and biomarker expressions.
            manual labor and automatically created multiple models   Moreover, many studies have confirmed that liver injury
            with uniform structures and components. Compared   caused by hepatotoxicity from drugs is one of the factors
            to the pure cell microarrays for drug screening, these   contributing to the numerous challenges associated with
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            models offer more complex and bionic characteristics. 112,113    drug diagnosis and management.  The renal system
            3D-bioprinted  microfluidic  models  allow  for  improved   is also necessary for drug screening and metabolism.
            interactions among cells, ECM, and relevant signaling   Hepatotoxicity and nephrotoxicity slow down the drug
            pathways, enabling the replication of cell behaviors and   development from discovery to the clinic, increasing the
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            disease features  in vivo. These models in which drug   risk of failure.
            reactions are observed directly can be manufactured in an   Lee et al.  selected PCL with low protein adsorption and
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            automated and controlled manner, reducing randomness   hydrophobicity as the printed channel shells to support the
            and enhancing the reliability of drug screening results.  internal reaction regions. Collagen hydrogel encapsulated




























            Figure 5. The process of drug development from discovery to clinical experiments. The red star represents 3D-bioprinted chips discussed in this review,
            which may replace animal models and 2D cultures in preclinical drug screening.


            Volume 10 Issue 3 (2024)                       185                                doi: 10.36922/ijb.1951
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