02208nas a2200289   4500000000100000000000100001008004100002653001900043653001900062653002300081653001800104653001900122653001800141100001400159700002400173700002100197700001600218700001600234700001500250700002400265245013100289856006300420300001100483490000800494520140200502022001401904                                       d10aROS generation10aDrug screening10ainflammatory model10amicrofluidics10amineralization10aperiodontitis1 aAbinaya R1 aKavitha Govarthanan1 aLakshmi Krishnan1 aKi-Taek Lim1 aMoeto Nagai1 aSuresh Rao1 aTuhin Subhra Santra00aA Biomimetic Microfluidic Triple-compartment Periodontium-on-chip for Investigation of Inflammatory Responses in Periodontitis  uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/smll.73973  ae739730 vn/a3 aWe 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.  a1613-6829