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Tooth-on-a-chip to engineer early dental epithelial-mesenchymal interaction
C Huang1,2, F Sanaei1, W Zhang3
1Department of Dentistry - Regenerative Biomaterials, Research Institute for Medical Innovation, Radboud University Medical Center, Philips van Leijdenlaan 25, 6525 EX, Nijmegen, the Netherlands.
Materials Today. Bio
|November 10, 2025
Summary
Researchers developed a novel "tooth-on-a-chip" to mimic tooth development. This micro-engineered device enables controlled interaction between dental epithelial (DE) and dental mesenchymal (DM) cells, advancing enamel regeneration strategies.
Area of Science:
- Biomaterials Engineering
- Developmental Biology
- Regenerative Medicine
Background:
- Tooth enamel regeneration is hindered by the loss of enamel-forming ameloblasts before tooth eruption.
- Existing in-vitro models lack precise control over dental epithelial (DE) and dental mesenchymal (DM) cell interactions and media conditions.
- Effective enamel regeneration requires recapitulating DE-DM interactions crucial for tooth morphogenesis.
Purpose of the Study:
- To develop a micro-engineered "tooth-on-a-chip" platform for controlled DE-DM interaction.
- To create a dual-medium microenvironment that independently perfuses lineage-specific media.
- To establish a model for studying early odontogenesis and amelogenesis for improved enamel regeneration.
Main Methods:
- Fabrication of a three-channel polydimethylsiloxane (PDMS) device using 3-D printing and soft lithography.
- Seeding dental mesenchymal (DM) cells within a fibrin hydrogel, followed by sequential seeding of dental epithelial (DE) cells.
- Utilizing quantitative PCR (qPCR), immunofluorescence, Alizarin Red staining, calcium assays, and SEM for analysis.
Main Results:
- DM cells formed a papilla-like core and secreted collagen, creating a niche for DE cells.
- Progressive up-regulation of odontogenic markers in DM cells and ameloblast differentiation in DE cells (AMELX expression) were observed.
- Spatially confined mineralization was confirmed at the engineered DE-DM interface.
Conclusions:
- The "tooth-on-a-chip" platform successfully recapitulates key aspects of early odontogenesis and amelogenesis.
- This controllable, dual-medium microenvironment offers a versatile tool for dissecting tooth development.
- The platform provides a foundation for accelerating true enamel-regeneration strategies.
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