{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:27:17Z","timestamp":1786512437819,"version":"build-2736575974"},"reference-count":56,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000867","name":"Robert Wood Johnson Foundation","doi-asserted-by":"publisher","award":["127275"],"award-info":[{"award-number":["127275"]}],"id":[{"id":"10.13039\/100000867","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Major advances in pulp biology, biomaterials, and tissue engineering have fuelled the development of regenerative strategies aimed at preserving or restoring pulp vitality. Despite this progress, the clinical translation of these discoveries remains limited or absent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Although there is a global agenda to reduce and replace animal use in medical research, we believe that a critical missing link in the translational pipeline of regenerative endodontics innovations is the lack of rigorously validated, clinically relevant preclinical models to use in advancing promising in vitro findings through regulatory processes to human application.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>While novel alternative methodologies (NAMs), including microfluidics, organoids, and organ\u2010on\u2010chip systems, offer human\u2010relevant in vitro models and are rapidly transforming early\u2010stage screening and mechanistic studies, they are currently insufficient to replicate the complex systemic elements provided by animal models, which are essential for demonstrating in vivo efficacy of regenerative therapies. Regulatory approval of devices, drugs, and biologics continues to require robust preclinical evidence generated in whole\u2010organism systems, particularly when complex interactions involving immunity, vascularisation, innervation, and aging are central to therapeutic success.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this perspective article, we discuss key scientific, methodological, and logistical considerations for the systematic development and validation of orthotopic animal models in regenerative endodontics research. We place particular emphasis on vital pulp treatment as a biologically and clinically relevant framework for studying pulp repair and in demonstrating the efficacy of novel therapies. We highlight the challenges that have hindered consensus in model selection and standardisation, and emphasise the need for coordinated transdisciplinary efforts to overcome these barriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We argue that prioritising standardised orthotopic vital pulp treatment models, in combination with evolving NAMs, represents a critical step to bridge the gap between mechanistic discoveries and clinical translation in regenerative endodontics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70238","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:31:52Z","timestamp":1786509112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Animal Research in Pulp Biology: A Missing Link in the Translation of Regenerative Endodontics Innovations"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4354-5162","authenticated-orcid":false,"given":"Simony H.","family":"Kataoka","sequence":"first","affiliation":[{"name":"Department of Endodontics and Periodontics School of Dental Medicine, University at Buffalo  Buffalo USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annayah","family":"Noorani","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry School of Dental Medicine, University at Buffalo  Buffalo USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3573-7945","authenticated-orcid":false,"given":"Asma Ban","family":"Owaiwid","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry School of Dental Medicine, University at Buffalo  Buffalo USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galib","family":"Ovik","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Jacobs School of Medicine, University at Buffalo  Buffalo USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-3866","authenticated-orcid":false,"given":"Huey\u2010Jiun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Jacobs School of Medicine, University at Buffalo  Buffalo USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8690-2379","authenticated-orcid":false,"given":"Henry F.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Division of Restorative Dentistry Dublin Dental University Hospital, Trinity College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3242-3433","authenticated-orcid":false,"given":"Te\u2010chung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Jacobs School of Medicine, University at Buffalo  Buffalo USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0388-5206","authenticated-orcid":false,"given":"Camila","family":"Sabatini","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry School of Dental Medicine, University at Buffalo  Buffalo USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"issue":"4","key":"e_1_2_7_2_1","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01113-18","article-title":"Moving Forward: Recent Developments for the Ferret Biomedical Research Model","volume":"9","author":"Albrecht R. 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