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However, a comprehensive investigation into the cytocompatibility of these materials, particularly concerning transcriptomic responses to monomer and ion release, has yet to be conducted. This study investigated model RBCs (80:20 UDMA:HEMA matrix, 62 vol% filler), including a fluorapatite (FA) containing composite (FA+, 9 vol%), to assess the effect of fluoride ion-releasing filler content on degree of conversion (DC%) and monomer release. Apparent water sorption and fluoride release were evaluated after 28\u2009d of storage in artificial saliva (pH 7 and pH 4) and distilled deionized water. Cytocompatibility was assessed using an XTT assay on human gingival fibroblasts (HGFs), and the expression of genes encoding DNA-repair and stress-response markers following composite exposure was analyzed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). RNA sequencing (RNA-seq) identified differentially expressed genes in response to FA+ and fluorapatite-free RBCs (FA\u2013). Unfilled specimens exhibited lower DC% and higher monomer release compared to the RBCs. FA+ specimens had the highest apparent water sorption, particularly after pH 7 artificial saliva storage. Fluoride release was most significant in acidic environments. UDMA reduced HGF viability compared to HEMA at all concentrations up to 5\u2009mM, but the polymerized RBCs caused no reduction compared to control HGFs. However, expression analysis by RT-qPCR of DNA-repair and stress-response markers following composite exposure revealed that UDMA reduced repair gene expression, whereas HEMA stimulated it. RNA-seq analysis revealed significant changes in gene expression profiles upon composite exposure, with enriched pathways related to ferroptosis and protein digestion. These findings highlight, for the first time, the potential for significant cellular responses even with limited composite component release from ion-releasing RBCs, underscoring the need for further research into the long-term biocompatibility of these materials.<\/jats:p>","DOI":"10.1177\/00220345261460387","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:22:25Z","timestamp":1786443745000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fluoride-Releasing Fillers Modulate the Response of Fibroblasts to Dental Composites"],"prefix":"10.1177","author":[{"given":"W.","family":"Al-Omairi","sequence":"first","affiliation":[{"name":"Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Restorative Dentistry Department, College of Dentistry, Wasit University, Al Kut, Wasit, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Altaie","sequence":"additional","affiliation":[{"name":"Restorative Dentistry Department, School of Dentistry, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8269-9123","authenticated-orcid":false,"given":"D. J.","family":"Wood","sequence":"additional","affiliation":[{"name":"Division of Oral Biology, School of Dentistry, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Werner","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3910-6377","authenticated-orcid":false,"given":"M. J.","family":"German","sequence":"additional","affiliation":[{"name":"School of Dental Sciences, Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Altaie A et al. 2020. 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