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The interplay between these diverse cell populations is pivotal for dental pulp tissue homeostasis and regeneration after carious infections and traumatic tooth lesions. Despite the great clinical need, comprehensive in vitro models that accurately recapitulate the complexity of the dental pulp are still missing, hampering the development of novel, faster, and more effective therapies. In this study, an innovative \u201ctooth\u2010on\u2010chip\u201d microfluidic device is presented to emulate the composition and three\u2010dimensional structure of the dental pulp tissue in vitro. Co\u2010culture of human dental pulp stem cells, odontoblast\u2010like cells, endothelial cells, and trigeminal neurones in this miniaturized system successfully reproduced the structural organization and physiology of the dental pulp. The microfluidic device integrated various compartments that allowed the generation of complex vascular and neuronal networks, the formation of stem cell perivascular niches, and the formation of an odontoblast\/dentine interface. The \u201ctooth\u2010on\u2010chip\u201d device represents a conceptual leap in replicating dental pulp physiology in vitro, offering a state\u2010of\u2010the\u2010art platform to study dental pulp physiology and pathology and serving as a benchmark to create more advanced tooth simulation systems.<\/jats:p>","DOI":"10.1002\/adhm.202502080","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T10:41:27Z","timestamp":1755772887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["An Innovative \u201cTooth\u2010On\u2010Chip\u201d Microfluidic Device Emulating the Structure and Physiology of the Dental Pulp Tissue"],"prefix":"10.1002","volume":"15","author":[{"given":"Alessandro","family":"Cordiale","sequence":"first","affiliation":[{"name":"Institute of Oral Biology Centre of Dental Medicine Medical Faculty University of Zurich  Zurich 8032 Switzerland"},{"name":"Department of Electronics Information and Bioengineering Politecnico di Milano  Milano 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Stanco","sequence":"additional","affiliation":[{"name":"Institute of Oral Biology Centre of Dental Medicine Medical Faculty University of Zurich  Zurich 8032 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Visone","sequence":"additional","affiliation":[{"name":"Department of Electronics Information and Bioengineering Politecnico di Milano  Milano 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Stadlinger","sequence":"additional","affiliation":[{"name":"Clinic of Cranio\u2010Maxillofacial and Oral Surgery Centre of Dental Medicine Medical Faculty University of Zurich  Zurich 8032 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierfrancesco","family":"Pagella","sequence":"additional","affiliation":[{"name":"Institute of Oral Biology Centre of Dental Medicine Medical Faculty University of Zurich  Zurich 8032 Switzerland"},{"name":"Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics Chemistry and Biology (IFM) Link\u00f6ping University  Link\u00f6ping 58183 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Rasponi","sequence":"additional","affiliation":[{"name":"Department of Electronics Information and Bioengineering Politecnico di Milano  Milano 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-9982","authenticated-orcid":false,"given":"Thimios A.","family":"Mitsiadis","sequence":"additional","affiliation":[{"name":"Institute of Oral Biology Centre of Dental Medicine Medical Faculty University of Zurich  Zurich 8032 Switzerland"},{"name":"Foundation for Research and Technology-Hellas (FORTH) University of Crete  Heraklion 70013 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23116356"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2022.01.002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.21-0086"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102405"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v029a16"},{"key":"e_1_2_9_6_1","first-page":"6356","volume":"11","author":"Lai C. 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