The teeth are vertebrate-specific and highly specialized organs performing fundamental functions of mastication and speech, the maintenance of which is crucial for orofacial homeostasis and is further linked to systemic health and human psychosocial well-being. However, with limited ability of self-repair, the teeth can often be impaired by traumatic, inflammatory and progressive insults, leading to high prevalence of tooth loss and defects worldwide. Regenerative medicine holds the promise to achieve physiological restoration of lost or damaged organs, and particularly an evolving framework of developmental engineering has pioneered for functional tooth regeneration by harnessing the odontogenic program. As a key event of tooth morphogenesis, mesenchymal condensation dictates dental tissue formation and patterning through cellular self-organization and signaling interaction with the epithelium, which provides a representative to decipher organogenetic mechanisms and can be leveraged for regenerative purposes. In this Review, we summarize how mesenchymal condensation spatiotemporally assembles from dental stem cells (DSCs) and sequentially mediates tooth development. We highlight condensation-mimetic engineering efforts and mechanisms based on ex vivo aggregation of DSCs, which have fulfilled functionally robust and physiologically relevant tooth regeneration after implantation in animals and in human. The discussion in this aspect will add to the knowledge of development-inspired tissue engineering strategies and will offer benefits to propel clinical organ regeneration.

中文翻译：

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牙齿发育和再生中的间充质凝聚：关注器官发生的转化方面

牙齿是脊椎动物特有的高度专业化的器官，执行咀嚼和言语的基本功能，其维护对于口面部稳态至关重要，并进一步与全身健康和人类社会心理健康相关。然而，由于自我修复能力有限，牙齿经常会因外伤、炎症和进行性损伤而受损，导致全球牙齿脱落和缺陷的发生率很高。再生医学有望实现丢失或受损器官的生理修复，特别是不断发展的发育工程框架通过利用牙源性程序开创了功能性牙齿再生的先河。作为牙齿形态发生的关键事件，间充质凝集通过细胞自组织和与上皮细胞的信号相互作用决定牙齿组织的形成和图案化，这为破译器官发生机制提供了代表，并可用于再生目的。在本综述中，我们总结了间充质凝集如何从牙科干细胞 (DSC) 时空组装并依次介导牙齿发育。我们重点介绍了基于 DSC 离体聚集的凝缩模拟工程工作和机制，它们在动物和人类植入后实现了功能强大和生理相关的牙齿再生。这方面的讨论将增加受发展启发的组织工程策略的知识，并将为推动临床器官再生提供益处。