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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\u2010infused 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\u2010specific gene expression profiling, protein expression (osteopontin, vimentin, and cementum protein\u20101), and immunocytochemistry. To create a periodontitis model, lipopolysaccharide was induced, and the inflammation was evaluated by THP\u20101 monocyte cell adhesion assay and measuring ROS generation. We further explored and confirmed the therapeutic efficacy through a rescue experiment, using potent anti\u2010inflammatory 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.<\/jats:p>","DOI":"10.1002\/smll.73973","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T07:21:27Z","timestamp":1780903287000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Biomimetic Microfluidic Triple\u2010compartment Periodontium\u2010on\u2010chip for Investigation of Inflammatory Responses in Periodontitis"],"prefix":"10.1002","volume":"22","author":[{"given":"Abinaya","family":"R","sequence":"first","affiliation":[{"name":"Department of Engineering Design Indian Institute of Technology Madras  India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavitha","family":"Govarthanan","sequence":"additional","affiliation":[{"name":"Department of Engineering Design Indian Institute of Technology Madras  India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2279-2339","authenticated-orcid":false,"given":"Lakshmi","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Department of Engineering Design Indian Institute of Technology Madras  India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2091-788X","authenticated-orcid":false,"given":"Ki\u2010Taek","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biosystems Engineering Kangwon National University  South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7852-7772","authenticated-orcid":false,"given":"Moeto","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Toyohashi University of Technology  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9247-6695","authenticated-orcid":false,"given":"Suresh","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Engineering Design Indian Institute of Technology Madras  India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9403-2155","authenticated-orcid":false,"given":"Tuhin Subhra","family":"Santra","sequence":"additional","affiliation":[{"name":"Department of Engineering Design Indian Institute of Technology Madras  India"},{"name":"School of Interdisciplinary Studies Indian Institute of Technology Madras  India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.23514"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368\u2010023\u201000258\u20109"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resourpol.2023.104466"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003\u20109969(60)90038\u20108"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12029"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12903\u2010022\u201002161\u2010x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46110724"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.709438"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1469414"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani13071223"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4LC00871E"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.18\u20100181"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.09.057"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA01459F"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2RA06018C"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5LC00459D"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781003014935"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-8953-4"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121247"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10404\u2010026\u201002875\u20102"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/dj12010005"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biosx.2022.100106"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/nano10122514"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dental.2025.12.003"},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","unstructured":"S.Abraham P.Gupta K.Govarthanan S.Rao andT. 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