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Given the rising therapeutic potential of Wnt\u2010targeted interventions in dental tissue engineering, elucidating these molecular interactions under pathological conditions is essential for developing\n                      <jats:italic>regenerative<\/jats:italic>\n                      therapeutics capable of simultaneously promoting reparative dentinogenesis while resolving inflammatory insults.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This perspective review aims to: (1) critically evaluate existing literature on lipopolysaccharide (LPS)\u2010mediated modulation of dental pulp stem cell (DPSC) fate, addressing inconsistencies in LPS concentrations, bacterial sources and inflammatory models; (2) identify methodological gaps in current standardisation and elucidate molecular mechanisms governing Wnt\/NF\u2010\u03baB signaling crosstalk in DPSCs under acute versus chronic inflammatory conditions; and (3) assess the therapeutic potential of GSK3\u03b2 inhibitors and exosome\u2010based interventions for dentine\u2010pulp regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>A comprehensive literature search was conducted across PubMed\/MEDLINE, Scopus and Web of Science Core Collection for publications through November 2025. Search strategies combined four thematic domains: (1) cell populations (\u201cdental pulp stem cell\u201d OR \u201cDPSC\u201d); (2) signaling pathways (\u201cWnt\u201d OR \u201c\u03b2\u2010catenin\u201d AND \u201cNF\u2010\u03baB\u201d OR \u201ccrosstalk\u201d); (3) biological processes (\u201codontogenic differentiation\u201d OR \u201cimmunomodulation\u201d OR \u201cmacrophage polarization\u201d); (4) inflammatory context (\u201cpulpitis\u201d OR \u201cinflammation\u201d OR \u201cLPS\u201d). Articles were screened for relevance to Wnt\/NF\u2010\u03baB interactions in dental pulp regeneration under inflammatory conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>Evidence demonstrates context\u2010dependent Wnt\/NF\u2010\u03baB crosstalk in DPSC fate specification. Low\u2010dose LPS (&lt;\u20091\u2009\u03bcg\/mL) stimulates reparative responses through coordinated Wnt\/NF\u2010\u03baB activation, whereas sustained high\u2010dose exposure (&gt;\u20091\u2009\u03bcg\/mL) suppresses Wnt signaling via NF\u2010\u03baB\u2010driven DKK1 upregulation, attenuating differentiation capacity. While no direct evidence links Wnt\/NF\u2010\u03baB crosstalk to DPSC self\u2010renewal, both pathways independently maintain stemness. Critically, DPSCs and macrophages exhibit reciprocal regenerative interactions: DPSC\u2010derived Wnt3a polarises macrophages toward the anti\u2010inflammatory M2 phenotype, while M2\u2010secreted Wnt7b enhances DPSC odontogenic differentiation by suppressing NF\u2010\u03baB expression. However, standardised inflammation models remain lacking, hindering comprehensive elucidation of context\u2010dependent mechanisms. Developing such models would clarify how inflammation temporally and spatially influences regenerative outcomes across clinical scenarios.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70169","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T12:37:44Z","timestamp":1777034264000},"page":"1743-1759","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inflammation\u2010Regeneration Axis of Dental Pulp Stem Cells: Wnt\/NF\u2010\u03baB Crosstalk"],"prefix":"10.1111","volume":"59","author":[{"given":"V.","family":"Rajasekar","sequence":"first","affiliation":[{"name":"Paediatric Dentistry, Faculty of Dentistry, Prince Philip Dental Hospital The University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Restorative Dental Sciences, Faculty of Dentistry The University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7642-3948","authenticated-orcid":false,"given":"M. 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