A Biomimetic Microfluidic Triple-compartment Periodontium-on-chip for Investigation of Inflammatory Responses in Periodontitis

We present an advanced periodontium model that recapitulates the structural and functional complexity of native periodontal tissue using a triple-compartment interlocking microfluidic chip. The model's functionality is enhanced by deposition of aligned gelatin nanofibers in the periodontium ligament channel, replicating Sharpey's fibers within the periodontal milieu, and lithium calcium silicate-infused gelatin nanofibers were deposited on the bone and cementum channels, replicating mineralization across cementoblast, periodontal ligament, and osteoblast layers. The osteogenic and cementogenic differentiation from human mesenchymal stem cells was performed and validated by RNA sequencing analysis, lineage-specific gene expression profiling, protein expression (osteopontin, vimentin, and cementum protein-1), and immunocytochemistry. To create a periodontitis model, lipopolysaccharide was induced, and the inflammation was evaluated by THP-1 monocyte cell adhesion assay and measuring ROS generation. We further explored and confirmed the therapeutic efficacy through a rescue experiment, using potent anti-inflammatory drugs such as metformin and curcumin, which suggests its potential for drug testing. Therefore, our platform can identify the appropriate drug regimens and aid in the development of medications with minimal adverse effects, thereby facilitating personalized therapy.