Tooth-On-A-Chip Models: Advances in Simulating Dental Pulp and Dentin Physiology Publisher



Jafari N ; Nejati O ; Darbouy M ; Derakhshani A ; Madani G ; Nejati A ; Zarepour A ; Khosravi A ; Zarrabi A
Source: TrAC - Trends in Analytical Chemistry Published:2026

Abstract

Tooth-on-a-chip (ToC) platforms are emerging in vitro models that simulate the complex structure and function of the dentin–pulp interface using microfluidic technologies. By integrating primary or stem cell-derived odontoblast-like cells, natural or synthetic scaffolds (e.g., dentin slices, collagen, gelatine methacrylate), and dynamic perfusion systems, these platforms provide a physiologically relevant environment for studying dental material interactions, inflammatory signaling, and regenerative processes. Unlike static 2D cultures or non-human in vivo models, ToC devices enable spatiotemporal control over biochemical gradients, shear stress, nutrient delivery, and real-time monitoring of cellular responses through integrated biosensors. These features make them uniquely suited for assessing cytotoxicity, bioactivity, and long-term effects of dental biomaterials and therapeutic compounds with high translational potential. Moreover, recent advances in multiplexed biosensing, 3D bioprinting, and organ-level integration (e.g., immune–vascular co-cultures) have extended the utility of ToC systems for modeling pathological conditions such as pulpitis, caries progression, and microbial-host interactions in a highly controlled manner. Despite ongoing challenges such as limited immune mimicry, lack of innervation, and standardization across platforms, ToC devices are rapidly emerging as next-generation alternatives for preclinical evaluation, biomaterials screening, and personalized endodontic medicine. This study explores advancements in ToC technology specifically aimed at modeling the environment of the dentin-pulp complex in teeth, highlighting recent design innovations and applications in dental tissue research and regenerative dentistry. Unlike broader organ-on-chip reviews, this review focuses on dental-specific ToC platforms, their translational potential, and key challenges for personalized endodontic applications. © 2026 Elsevier B.V.