An Innovative “Tooth‐On‐Chip” Microfluidic Device Emulating the Structure and Physiology of the Dental Pulp Tissue

Abstract The dental pulp is a highly vascularized and innervated connective tissue composed of various cell types, including fibroblasts, odontoblasts, mesenchymal stem cells, neuronal, and endothelial cells. The interplay between these diverse cell populations is pivotal for dental pulp tissue homeostasis and regeneration after carious infections and traumatic tooth lesions. Despite the great clinical need, comprehensive in vitro models that accurately recapitulate the complexity of the dental pulp are still missing, hampering the development of novel, faster, and more effective therapies. In this study, an innovative “tooth‐on‐chip” microfluidic device is presented to emulate the composition and three‐dimensional structure of the dental pulp tissue in vitro. Co‐culture of human dental pulp stem cells, odontoblast‐like cells, endothelial cells, and trigeminal neurones in this miniaturized system successfully reproduced the structural organization and physiology of the dental pulp. The microfluidic device integrated various compartments that allowed the generation of complex vascular and neuronal networks, the formation of stem cell perivascular niches, and the formation of an odontoblast/dentine interface. The “tooth‐on‐chip” device represents a conceptual leap in replicating dental pulp physiology in vitro, offering a state‐of‐the‐art platform to study dental pulp physiology and pathology and serving as a benchmark to create more advanced tooth simulation systems.