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 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.

中文翻译：

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芯片上的牙齿：一种微生理模型系统，模仿了生物材料与牙齿的生物界面。

对于用于治疗的生物材料，牙齿具有独特的构造。牙髓内部的细胞通过钙化的可渗透膜与生物材料间接接触，该膜由牙本质基质和数千个牙本质小管（直径约2μm）形成。尽管已经对牙髓对生物材料的细胞毒性反应进行了广泛的研究，但仍缺乏模仿牙本质-牙髓界面并能够更好地理解生物材料对活牙髓的形态，代谢和功能影响的体外模型系统细胞。为了解决这一短缺问题，我们在这里开发了一种芯片上器官模型系统，该系统将直接培养在牙本质壁上的细胞整合到微流控设备中，该设备复制了牙本质与牙髓界面的某些结构和动力学。芯片上的牙齿由模制的聚二甲基硅氧烷（PDMS）制成，其设计由两个由牙本质碎片隔开的小室组成。为了表征牙髓细胞对片上牙科材料的反应，将来自根尖乳头（SCAP）的干细胞培养在牙源性培养基中，并接种到牙本质表面，并使用活细胞显微镜观察。接下来，为了评估片上牙齿作为材料测试的平台，对临床上使用的标准牙科材料（甲基丙烯酸2-羟乙酯-HEMA，磷酸-PA和Adper-Scotchbond-SB）进行了细胞毒性和细胞形态学测试以及芯片上的代谢活性，并与标准的芯片外对照进行比较。所有牙科材料在片上和片外系统中均具有以下细胞毒性作用：HEMA> SB> PA（p <0.05），而且细胞在片上的代谢活性始终高于片外（p <0.05）。此外，片上牙齿能够实时跟踪微型设备中形成的模型混合层（HL）中的明胶分解活性，这表明牙髓细胞比内源蛋白酶对HL中蛋白水解活性的贡献更大。 。总之，片上牙齿是一个新颖的平台，可复制牙髓-牙本质界面的近乎生理条件，并使活细胞成像能够研究牙髓细胞对生物材料的反应。这表明牙髓细胞比内源蛋白酶对HL中蛋白水解活性的贡献更大。总之，片上牙齿是一个新颖的平台，可复制牙髓-牙本质界面的近乎生理条件，并使活细胞成像能够研究牙髓细胞对生物材料的反应。这表明牙髓细胞比内源蛋白酶对HL中蛋白水解活性的贡献更大。总之，片上牙齿是一种新颖的平台，可复制牙髓-牙本质界面的近乎生理的条件，并使活细胞成像能够研究牙髓细胞对生物材料的反应。