Numerous approaches have been introduced to regenerate artificial dental tissues. However, conventional approaches are limited when producing a construct with three-dimensional patient-specific shapes and compositions of heterogeneous dental tissue. In this research, bioprinting technology was applied to produce a three-dimensional dentin-pulp complex with patient-specific shapes by inducing localized differentiation of human dental pulp stem cells within a single structure. A fibrin-based bio-ink was designed for bioprinting with the human dental pulp stem cells. The effects of fibrinogen concentration within the bio-ink were investigated in terms of printability, human dental pulp stem cell compatibility, and differentiation. The results show that micro-patterns with human dental pulp stem cells could be achieved with more than 88% viability. Its odontogenic differentiation was also regulated according to the fibrinogen concentration. Based on these results, a dentin-pulp complex having patient-specific shape was produced by co-printing the human dental pulp stem cell-laden bio-inks with polycaprolactone, which is a bio-thermoplastic used for producing the overall shape. After culturing with differentiation medium for 15 days, localized differentiation of human dental pulp stem cells in the outer region of the three-dimensional cellular construct was successfully achieved with localized mineralization. This result demonstrates the possibility to produce patient-specific composite tissues for tooth tissue engineering using three-dimensional bioprinting technology.

中文翻译：

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三维牙本质-牙髓复合物的生物打印与人牙髓干细胞的局部分化。


已经引入了许多方法来再生人造牙组织。然而，在生产具有三维患者特定形状和异质牙组织成分的结构时，传统方法受到限制。在这项研究中，生物打印技术被应用于通过诱导单一结构内的人类牙髓干细胞的局部分化来生产具有患者特定形状的三维牙本质-牙髓复合物。基于纤维蛋白的生物墨水被设计用于人类牙髓干细胞的生物打印。研究了生物墨水中纤维蛋白原浓度对可打印性、人牙髓干细胞相容性和分化的影响。结果表明，用人牙髓干细胞制作的微模型的存活率超过 88%。其牙源性分化也根据纤维蛋白原浓度进行调节。基于这些结果，通过将载有牙髓干细胞的生物墨水与聚己内酯（一种用于产生整体形状的生物热塑性塑料）共同打印，生产出具有患者特定形状的牙本质-牙髓复合物。用分化培养基培养15天后，三维细胞结构外部区域的人牙髓干细胞成功实现局部分化并局部矿化。这一结果证明了利用三维生物打印技术生产用于牙齿组织工程的患者特异性复合组织的可能性。