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The tooth on-a-chip: a microphysiologic model system mimicking the biologic interface of the tooth with biomaterials.

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 the dentin matrix and several thousands of dentinal tubules (?2 ?m in diameter). 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 and enable 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 microfluidic device that 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 cells from the apical papilla (SCAPs) were cultured in odontogenic medium and seeded onto the dentin surface, and observed using live-cell microscopy. Next, to evaluate the tooth-on-a-chip as a platform for materials testing, 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 gelatinolytic activity in a model hybrid layer (HL) formed in the microdevice, which suggests that dental pulp cells may contribute to the proteolytic activity in the HL more than endogenous proteases. 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.

SUBMITTER: Franca CM

PROVIDER: S-EPMC7395925 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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The tooth on-a-chip: a microphysiologic model system mimicking the biologic interface of the tooth with biomaterials.

França Cristiane Miranda CM Tahayeri Anthony A Rodrigues Nara Sousa NS Ferdosian Shirin S Puppin Rontani Regina Maria RM Sereda Grigoriy G Ferracane Jack L JL Bertassoni Luiz E LE

Lab on a chip 20191219 2

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 the dentin matrix and several thousands of dentinal tubules (∼2 μm in diameter). 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 and enable an improved ...[more]

PMID: 31854401

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Project description:Functional loads on an organ induce tissue adaptations by converting mechanical energy into chemical energy at a cell-level. The transducing capacity of cells alters physico-chemical properties of tissues, developing a positive feedback commonly recognized as the form-function relationship. In this study, organ and tissue adaptations were mapped in the bone-tooth complex by identifying and correlating biomolecular expressions to physico-chemical properties in rats from 1.5 to 15 months. However, future research using hard and soft chow over relevant age groups would decouple the function related effects from aging affects. Progressive curvature in the distal root with increased root resorption was observed using micro X-ray computed tomography. Resorption was correlated to the increased activity of multinucleated osteoclasts on the distal side of the molars until 6 months using tartrate resistant acid phosphatase (TRAP). Interestingly, mononucleated TRAP positive cells within PDL vasculature were observed in older rats. Higher levels of glycosaminoglycans were identified at PDL-bone and PDL-cementum entheses using alcian blue stain. Decreasing biochemical gradients from coronal to apical zones, specifically biomolecules that can induce osteogenic (biglycan) and fibrogenic (fibromodulin, decorin) phenotypes, and PDL-specific negative regulator of mineralization (asporin) were observed using immunohistochemistry. Heterogeneous distribution of Ca and P in alveolar bone, and relatively lower contents at the entheses, were observed using energy dispersive X-ray analysis. No correlation between age and microhardness of alveolar bone (0.7 ± 0.1 to 0.9 ± 0.2 GPa) and cementum (0.6 ± 0.1 to 0.8 ± 0.3 GPa) was observed using a microindenter. However, hardness of cementum and alveolar bone at any given age were significantly different (P<0.05). These observations should be taken into account as baseline parameters, during development (1.5 to 4 months), growth (4 to 10 months), followed by a senescent phase (10 to 15 months), from which deviations due to experimentally induced perturbations can be effectively investigated.

Dataset Information

The tooth on-a-chip: a microphysiologic model system mimicking the biologic interface of the tooth with biomaterials.

Publications

The tooth on-a-chip: a microphysiologic model system mimicking the biologic interface of the tooth with biomaterials.

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