# Three-Dimensional-Bioprinted Liver Chips and Challenges
## 5 Concluding Remarks  
The liver is the central hub of xenobiotic metabolism, filtering, and detoxification, and is susceptible to drug- and cosmetic-induced toxicity. Microfluidic chips, as high-throughput platforms, enable the culture of multiple cells on a single chip, facilitating the study of cell-cell interactions and their reactions for applied medicine (e.g., modeling of drug absorption and immune response in an interconnected network of liver-gut-kidney [87]). Three-dimensional bioprinting can contribute to multi-cell cultures using multi-nozzle configurations to print different cells and microfluidic chips simultaneously with no need for a secondary cell-seeding process. Moreover, the advent of coaxial printing and sacrificial printing allowed the fabrication of vascularized liver-on-chip platforms, enabling the study and real-time analysis of liver-specific phenomena (e.g., zonation) [86].  
Three-dimensional bioprinting offers precision in fabrication and versatility in design, ultimately facilitating the manufacture of intricate 3D organ-mimicking cell structures on chips. Nonetheless, none of the available 3D bioprinting techniques is the best. Even though light-induced methods can produce complex 3D structures with high resolutions, scalability, limited material selection, and the high cost are still challenging. Furthermore, additional studies are necessary to determine the possible photo-induced damage to cells in the short and long term [54]. Nozzle-based bioprinters, on the other hand, are readily available and cost-effective methodologies. However, moderate resolution and shear stress (leading to cell damage and low cell viability) are their major challenges [54]. Future studies can aim to integrate multiple 3D bioprinting methods to obtain a better resolution and high throughput. In addition, the development of human-on-chip platforms can substantially increase the capability of OOC platforms to achieve a multi-aspect study of diseases and drug responses.  
Conceptualization, S.R.D. and S.T.; writing--original draft preparation, S.R.D. and B.O.; writing--review and editing, N.M. and S.T.; supervision, S.T.; project administration, S.T.; funding acquisition, S.T. All authors have read and agreed to the published version of the manuscript.  
**Funding:** This article was funded by Tubitak 2232 International Fellowship for the Outstanding Researchers Award (118C391), Alexander von Humboldt Research Fellowship for Experienced Researchers, Marie Sklodowska-Curie Individual Fellowship (101003361), and Royal Academy Newton-Katip Celebi Transforming Systems Through Partnership award (120N019).  
**Institutional Review Board Statement:** Not applicable as this article does not involve any human/animal tests.  
**Informed Consent Statement:** Not applicable as this article does not involve any human/animal tests.  
**Data Availability Statement:** Data sharing is not applicable to this article as no new data were created or analyzed in this study.  
**Acknowledgments:** S.T. acknowledges the Tubitak 2232 International Fellowship for the Outstanding Researchers Award (118C391), Alexander von Humboldt Research Fellowship for Experienced Researchers, Marie Sklodowska-Curie Individual Fellowship (101003361), and Royal Academy Newton-Katip Celebi Transforming Systems Through Partnership award (120N019) for financial support of this research. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the TUBITAK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.  
**Conflicts of Interest:** The authors declare no conflict of interest.