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      The Application of Organs-on-a-Chip in Dental, Oral, and Craniofacial Research

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          Abstract

          The current development of microfluidics-based microphysiological systems (MPSs) will rapidly lead to a paradigm shift from traditional static 2-dimensional cell cultivation towards organized tissue culture within a dynamic cellular milieu. Especially organs-on-a-chip (OoCs) can very precisely re-create the mechanical and unique anatomical structures of the oral environment. This review provides an introduction to such technology, from commonly used chip materials and fabrication methods to the application of OoC in in vitro culture. OoCs are advantageous because of their small-scaled culture environment, the highly controlled dynamic experimental conditions, and the likeness to the in vivo structure. We specifically focus on current chip designs in dental, oral, and craniofacial (DOC) research. Also, future perspectives are discussed, like model standardization and the development of integrated platforms with advanced read-out functionality. By doing so, it will be possible for OoCs to serve as an alternative for animal testing and to develop highly predictive human models for clinical experiments and even personalized medicine.

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          Most cited references59

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          Modeling Development and Disease with Organoids.

          Recent advances in 3D culture technology allow embryonic and adult mammalian stem cells to exhibit their remarkable self-organizing properties, and the resulting organoids reflect key structural and functional properties of organs such as kidney, lung, gut, brain and retina. Organoid technology can therefore be used to model human organ development and various human pathologies 'in a dish." Additionally, patient-derived organoids hold promise to predict drug response in a personalized fashion. Organoids open up new avenues for regenerative medicine and, in combination with editing technology, for gene therapy. The many potential applications of this technology are only beginning to be explored.
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            The origins and the future of microfluidics.

            The manipulation of fluids in channels with dimensions of tens of micrometres--microfluidics--has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.
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              Reconstituting organ-level lung functions on a chip.

              Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.
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                Author and article information

                Journal
                J Dent Res
                J Dent Res
                JDR
                spjdr
                Journal of Dental Research
                SAGE Publications (Sage CA: Los Angeles, CA )
                0022-0345
                1544-0591
                1 February 2023
                April 2023
                : 102
                : 4
                : 364-375
                Affiliations
                [1 ]Department of Dentistry–Regenerative Biomaterials, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands
                [2 ]The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China
                [3 ]Department of Biochemistry, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands
                [4 ]Department of Implantology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
                Author notes
                [*]X.F. Walboomers, Department of Dentistry–Regenerative Biomaterials, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Ph van Leijdenlaan 25, Nijmegen, 6525 EX, The Netherlands. Email: Frank.Walboomers@ 123456radboudumc.nl
                [*]W. Ji, Department of Implantology, School & Hospital of Stomatology, Wuhan University, Luoyu Road 237, Wuhan, Hubei 430079, China. Email: wei.ji@ 123456whu.edu.cn
                Author information
                https://orcid.org/0000-0002-4022-7643
                https://orcid.org/0000-0002-1473-5222
                Article
                10.1177_00220345221145555
                10.1177/00220345221145555
                10031637
                36726271
                84625e4c-3ceb-4009-922b-f66b3ff7ccb5
                © International Association for Dental Research and American Association for Dental, Oral, and Craniofacial Research 2023

                This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Funding
                Funded by: National Natural Science Foundation of China, FundRef https://doi.org/10.13039/501100001809;
                Award ID: No.82170931
                Funded by: China Scholarship Council, FundRef https://doi.org/10.13039/501100004543;
                Award ID: No.202106270158
                Categories
                Reviews
                Critical Reviews in Oral Biology & Medicine
                Custom metadata
                ts1

                pulp biology,mucosal immunity,biofilm(s),dentin,mineralized tissue/development,odontoblast(s)

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