Biocompatibility and Cytotoxicity of Universal Dental Adhesives on Human Dental Pulp Cells: A Systematic Review of in Vitro Studies

Background: Unpolymerized monomers released from resin-based universal dental adhesives may diffuse through dentinal tubules towards the pulp, and cell-culture studies suggest that some monomers can impair pulp-cell function. Previous systematic reviews have addressed resin composites or dental adhesives in general, often with mixed cell types; to our knowledge none has restricted its question to human dental pulp cells exposed to universal adhesives. How the in vitro effects of universal adhesives on human pulp cells compare between products and experimental conditions therefore remains unclear. Objective: To systematically review in vitro studies reporting the effects of universal dental adhesives on human dental pulp cells, compared with untreated controls or other adhesives, on cell viability/metabolic activity, cell death and inflammatory mediators, and to describe how these outcomes varied with the experimental conditions reported. Methods: PubMed, ScienceDirect and Google Scholar were last searched on for in vitro studies published between 1 January 2020 and 23rd April 2026. English-language, full-text studies using human dental pulp cells and universal adhesives were eligible. Two reviewers independently screened studies and extracted data. Methodological quality and completeness of reporting were appraised with an author-developed six-domain checklist adapted from CONSORT items (not a validated risk-of-bias tool). We synthesized findings narratively; we did not conduct a meta-analysis or formal certainty-of-evidence grading. The review was reported according to PRISMA 2020. This review was not registered in PROSPERO or any other registry Results: Seven in vitro studies were included (five used human dental pulp stem cells; two used human pulp cells). Viability or metabolic activity was assessed by MTT (five studies), WST-1 (one), trypan blue (one) and Live/Dead staining (one); flow cytometry was used in two. Exposure ranged from 24 hours to 7 days, and three studies assessed more than one time point. Three studies measured inflammatory mediators (ELISA, MAGPIX or qPCR). Results differed markedly between products and between studies. At 24 hours, metabolic activity was close to control for Single Bond Universal and Clearfil Universal Bond Quick but markedly reduced for OptiBond Universal, ZipBond Universal, Bond Force II and Futurabond DC. Cytokine changes were reported after ZipBond Universal (IL-1?, IL-6, TNF-? and IL-10 increased) and Single Bond Universal (IL-8 increased). Findings for isolated monomers depended on concentration and could not be generalized to commercial adhesives. Conclusion: Across seven heterogeneous in vitro studies, universal adhesives affected human pulp cells differently by product, concentration, assay, and exposure time. These data do not identify compositional determinants of biocompatibility, do not allow products to be ranked, and are not evidence of clinical pulpal safety or harm. Standardized protocols and clinical studies are needed.