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The tooth on-a-chip: a microphysiologic model system mimicking the pulp-dentin interface and its interaction with biomaterials

Cristiane Miranda França, Anthony Tahayeri, Nara Sousa Rodrigues, Shirin Ferdosian, Regina Puppin-Rontani, Jack L. Ferracane, View ORCID ProfileLuiz E. Bertassoni
doi: https://doi.org/10.1101/748053
Cristiane Miranda França
1Department of Restorative Dentistry, School of Dentistry, Oregon Health & Science University, Portland, OR, USA
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Anthony Tahayeri
1Department of Restorative Dentistry, School of Dentistry, Oregon Health & Science University, Portland, OR, USA
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Nara Sousa Rodrigues
2Post-Graduation Program in Dentistry, Federal University of Ceará, Fortaleza, Ceará, Brazil
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Shirin Ferdosian
1Department of Restorative Dentistry, School of Dentistry, Oregon Health & Science University, Portland, OR, USA
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Regina Puppin-Rontani
3School of Dentistry, University of Campinas, Piracicaba, Sao Paulo, Brazil
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Jack L. Ferracane
1Department of Restorative Dentistry, School of Dentistry, Oregon Health & Science University, Portland, OR, USA
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Luiz E. Bertassoni
1Department of Restorative Dentistry, School of Dentistry, Oregon Health & Science University, Portland, OR, USA
4Center for Regenerative Medicine, School of Medicine, Oregon Health & Science University, Portland, OR, USA
5Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, Portland, OR, USA
6Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Portland, OR, USA
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  • ORCID record for Luiz E. Bertassoni
  • For correspondence: bertasso@ohsu.edu
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Abstract

The tooth has a unique configuration with respect to biomaterials that are used for its treatment. Cells inside of the dental pulp interface indirectly with biomaterials via a calcified permeable membrane, formed by a dentin barrier which is composed of several thousands of dentinal tubules (~2 µm in diameter) connecting the dental pulp tissue to the outer surface of the tooth. Although the cytotoxic response of the dental pulp to biomaterials has been extensively studied, there is a shortage of in vitro model systems that mimic the dentin-pulp interface, enabling an improved understanding of the morphologic, metabolic and functional influence of biomaterials on live dental pulp cells. To address this shortage, here we developed an organ-on-a-chip model system which integrates cells cultured directly on a dentin wall within a microdevice which replicates some of the architecture and dynamics of the dentin-pulp interface. The tooth-on-a-chip is made out of molded polydimethylsiloxane (PDMS) with a design consisting of two chambers separated by a dentin fragment. To characterize pulp cell responses to dental materials on-chip, stem cell-derived odontoblasts were seeded onto the dentin surface, and observed using live-cell microscopy. Standard dental materials used clinically (2-hydroxyethylmethacrylate - HEMA, Phosphoric Acid - PA, and Adper-Scotchbond - SB) were tested for cytotoxicity, cell morphology and metabolic activity on-chip, and compared against standardized off-chip controls. All dental materials had cytotoxic effects in both on-chip and off-chip systems in the following order: HEMA>SB>PA (p<0.05), and cells presented consistently higher metabolic activity on-chip than off-chip (p<0.05). Furthermore, the tooth-on-a-chip enabled real-time tracking of odontoblast monolayer formation, remodeling, and death in response to biomaterial treatments, and gelatinolytic activity in a model hybrid layer (HL) formed in the microdevice. In conclusion, the tooth-on-a-chip is a novel platform that replicates near-physiologic conditions of the pulp-dentin interface, and enables live-cell imaging to study dental pulp cell response to biomaterials.

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Posted August 28, 2019.
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The tooth on-a-chip: a microphysiologic model system mimicking the pulp-dentin interface and its interaction with biomaterials
Cristiane Miranda França, Anthony Tahayeri, Nara Sousa Rodrigues, Shirin Ferdosian, Regina Puppin-Rontani, Jack L. Ferracane, Luiz E. Bertassoni
bioRxiv 748053; doi: https://doi.org/10.1101/748053
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The tooth on-a-chip: a microphysiologic model system mimicking the pulp-dentin interface and its interaction with biomaterials
Cristiane Miranda França, Anthony Tahayeri, Nara Sousa Rodrigues, Shirin Ferdosian, Regina Puppin-Rontani, Jack L. Ferracane, Luiz E. Bertassoni
bioRxiv 748053; doi: https://doi.org/10.1101/748053

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