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hiPSC-Derived Gingival Epithelium-On-Chip for Modeling Inflammation and Immune Response
Yang Zhou1, Yunshan Liu1, Xiaojie Lin1
1Department of Materials Science and Engineering, College of Engineering, University of Washington, 1400 NE Campus Parkway, Seattle, Washington 98195, United States.
ACS Applied Materials & Interfaces
|March 18, 2026
Summary
A new gingival epithelium-on-chip (GEoC) platform using stem cells enhances inflammatory signal detection. This scalable model improves the study of oral inflammation and drug screening for anti-inflammatory treatments.
Area of Science:
- Oral biology
- Biomedical engineering
- Immunology
Background:
- The gingival epithelium is crucial for oral inflammation responses.
- Existing in vitro models have limitations in scalability, donor variability, and inflammatory signal detection.
Purpose of the Study:
- To develop a scalable and controllable gingival epithelium-on-chip (GEoC) platform.
- To enhance sensitivity for detecting inflammatory signals and evaluating anti-inflammatory interventions.
Main Methods:
- Utilized human induced pluripotent stem cell (hiPSC)-derived oral keratinocytes in a microfluidic device with a spatial calcium gradient.
- Cultured cells in a three-dimensional (3D) microenvironment to promote differentiation.
- Stimulated the model with lipopolysaccharide (LPS) and assessed pro-inflammatory cytokine responses.
Main Results:
- The GEoC platform demonstrated amplified pro-inflammatory cytokine responses compared to 2D cultures.
- Achieved a substantially expanded dynamic range for inflammatory output detection.
- Successfully discriminated immunomodulatory effects of rapamycin and stannous fluoride, which were muted in 2D systems.
Conclusions:
- The GEoC platform offers enhanced sensitivity and a broader dynamic range for studying oral inflammation.
- This model supports reproducible and comparative evaluation of anti-inflammatory agents using a renewable stem cell source.
- The GEoC platform is a valuable tool for immunocompetent epithelial-immune inflammation research.

