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




            neuroblastoma tissue on the chip. The bioink was printed on   Several issues need to be addressed to obtain predictive
            the central groove, and the above procedures were repeated   and cogent results from microarrays: (ⅰ) The appropriate
            after printing vessels with sacrificial bioink (Pluronic). In   quantity of cells required in microdroplets needs to be
            order to distribute the ECs evenly on the channel walls, an   determined. (ⅱ) Consistent culture conditions should be
            orbital oscillator was integrated to form the vascular wall.   maintained in different microdroplets. (ⅲ) Taking high
            The fully automated process eliminated the manual steps   throughput as the prerequisite, further development of
            of the traditional tumor-on-a-chip and was expected to   structural complexity is necessary.
            enable high-throughput screening (Figure 6E).
                                                               5. Prospects in precision medicine
               Zhang et al.  printed the vessel model with branches
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            in GelMA hydrogel, and inoculated erythrocytes following   The 3D-bioprinted microfluidic model can be used not
            perfusion with whole blood for a while. The coagulant was   only in preclinical stages but also in the evaluation of drug
            added in one branch to enable the thrombus formation   therapy effects on different patients. To provide effective
            to ensure perfusability of another branch. The addition   treatment options for different patients, it is important
            of thrombolytic agents and co-culture with fibroblasts   for the model to incorporate more characteristics from
            confirmed  the  potential  application  in  pathological   patient microenvironments. Drug treatment can be
                                                               tailored based on specific pathogenesis and dosage for
            models, including thrombus, thrombolysis, fibrosis, and   each person. The inaccurately predictive results of animal
            related drug studies.                              models, the gap between animal models and humans, and

               The disease-on-a-chip will no longer be limited to   the high experimental cost promote the advancement
            reproducing the lesion locations. Taking the artificial   of human-derived  in  vitro models using emerging
            tumor model as an example, the interaction between tumor   manufacturing technologies. Precision medicine utilizes
            and vessels that plays a role in tumor metastasis gives   pathological information such  as genetic  materials to
            impetus to developing a vascularized tumor-on-a-chip,   distinguish specific patients from other patients with
            which enhances physiological correlation and exhibits the   similar disease characteristics and match them with
            potential to screen drugs for inhibiting angiogenesis and   personalized treatment options. These individual-based
            tumor metastasis.                                  treatments result in lower dosages, fewer side effects,
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                                                               and less toxicity.  Personalized human-derived in vitro
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            4.3. 3D-bioprinted microfluidic arrays             models are the perfect solution for the implementation
            Microfluidic arrays with multiple reaction sites require   of personalized medicine. The research of patient-derived
            repeated manual operations. Nevertheless, inkjet-based   models, multi-organ chips, and drug therapy lays a solid
            bioprinting provides a solution that fully automates both   foundation for precision medicine.
            cell inoculation and model formation, thereby realizing   5.1. Patient-oriented models
            high-throughput analysis.
                                                               In  the fabrication of  bioprinted OOCs, ordinary
               Microarrays have ten-fold reaction sites generated by   functional  hydrogels  and  animal-derived  bioinks  are
            pre-mixed bioinks. This program realizes high-throughput   replaced by human-derived bioinks, such as dECM
            drug screening and minimal reagent consumption.    extracted from human tissues.  The quality of prepared
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            Multiple  microarrays  in which an  ejected droplet  is  a   bioink is critical for the maturation of the models. When
            reaction site are  always incorporated  with  automated   the bioink exhibits significant individual differences, it
            3D inkjet-based bioprinting. Inkjet-based bioprinting   contains individual genetic information and expresses
            is effective in printing droplets with cells, whereas   functional protein. As a result, the patient-derived models
            the resulting bioprinted constructs are simple at the    constructed from such bioink have more individual
            cellular level.                                    specificity. Consequently, optimal treatment can be
                                                               identified to achieve the goal of precision medicine.
               In this study, 400 single-cell microreactors were created   Moreover, the cultured cells could be substituted by tissues
            using inkjet bioprinting on a microfluidic chip after the   excised from each patient. Constructs from patients with
            printing parameters were optimized. However, each   the same disease are fabricated to explore the individual
            microreactor contained cancer cells with weak migration   variability according to their drug response. Although
            ability, and the reaction in each microreactor was unable to   patient-derived chips may not fully replicate genetic
            recapitulate that in organs. Ultimately, paclitaxel at varying   information, the parental tumor phenotype and the
            concentrations,  which  was found  to be dose-dependent,   heterogeneity that decide the variation of drug resistance
            was applied on this chip.                          are retained.  As a result, the models have high accuracy
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            Volume 10 Issue 3 (2024)                       188                                doi: 10.36922/ijb.1951
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