{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:52:27Z","timestamp":1787014347206,"version":"build-2736575974"},"reference-count":67,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pulp responds to disease and trauma through inflammation which modulates the tooth's ability to instigate healing mechanisms. In\u00a0vitro human dental pulp cell (HDPC) culture models are widely used to study the tooth's response to pro\u2010inflammatory stimuli.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The purpose of this review is to generate a structured appraisal of in\u00a0vitro research methodologies to study HDPC cultures in a state of inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>In this narrative review the Scopus, PubMed and Google Scholar databases were searched to identify studies reporting the use of HDPC cultures in\u00a0vitro in inflammation\u2010associated research until December 2024. The dataset initially identified 642 publications, which were manually screened to identify 246 relevant studies for inclusion and methodologically mined for information on: (i) study purpose, (ii) source and characterisation of cells, (iii) pro\u2010inflammatory stimuli used and (iv) assays and markers used to characterise the inflammatory response. The collected data underpinned this review.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Most published studies aimed to characterise HDPC responses to a range of pro\u2010inflammatory stimulants which included bacterial components (lipopolysaccharides [LPS] and lipoteichoic acids [LTA]), cytokines and biomaterials. These stimulations were studied: to characterise their effect in the development of new scaffolds and dental (bio)materials and to mimic the in\u00a0vivo environment. Various tooth sources were used to establish HDPC cultures, and predominantly, cells were isolated using the pulp tissue explant technique. The most frequently used stimulant and concentrations were LPS at 1 and 10\u2009\u03bcg\/mL. The time for cell stimulation prior to inflammatory response assay varied from 15\u2009min to 10\u2009days. Inflammatory assessments were performed using quantitative polymerase chain reaction (qPCR), Western Blotting, enzyme\u2010linked immunosorbent assay (ELISA) and high\u2010throughput assays targeting archetypical cytokines and dentinogenic and mineralisation\u2010associated molecules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This review highlights the broad range of experimental conditions used to study HDPC inflammatory responses in\u00a0vitro and combines these data to identify a framework for a consensus and a more uniform experimental approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Standardisation of in\u00a0vitro experimental conditions to evaluate the pulps response to inflammatory stimuli would enhance research rigour and improve clinical translation to ultimately inform patient treatment and outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70004","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T12:04:02Z","timestamp":1753445042000},"page":"1670-1680","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Critical Review of In\u00a0Vitro Methodologies for Studying Inflammatory Responses in Human Dental Pulp Cell Cultures"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1277-6194","authenticated-orcid":false,"given":"Shelly","family":"Arora","sequence":"first","affiliation":[{"name":"School of Dentistry IMU University  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn","family":"Gilroy","sequence":"additional","affiliation":[{"name":"Sir John Walsh Research Institute, Faculty of Dentistry University of Otago  Dunedin 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