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Lookup NU author(s): Widad AL-Omairi, Daniel Wood, Dr Andreas Werner, Dr Matthew GermanORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
To reduce secondary caries-related restoration failure, ion-releasing fillers are being incorporated into resin-based composites (RBCs). 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 d 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–). 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 mM, 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.
Author(s): Al-Omairi W, Altaie A, Wood DJ, Werner A, German MJ
Publication type: Article
Publication status: Published
Journal: Journal of Dental Research
Year: 2026
Pages: Epub ahead of print
Online publication date: 11/08/2026
Acceptance date: 29/05/2026
Date deposited: 23/06/2026
ISSN (print): 0022-0345
ISSN (electronic): 1544-0591
Publisher: Sage Publications
URL: https://doi.org/10.1177/00220345261460387
DOI: 10.1177/00220345261460387
Data Access Statement: The data presented in this study will be made available in a public repository (10.25405/data.ncl.32347719) upon acceptance. Raw RNA-sequencing data (FASTQ files) have been deposited in the NCBI Sequence Read Archive (SRA) under BioProject accession number PRJNA1472904 and are publicly available at https:// www.ncbi.nlm.nih.gov/bioproject/PRJNA1472904.
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