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Record W4415706301 · doi:10.1016/j.actbio.2025.10.061

Pathways of neutrophil enzymatic degradation of resin-based composites and adhesives

2025· article· en· W4415706301 on OpenAlexafffund
Yuval Peled, Aya Ragheai, Zach Gouveia, Cameron A. Stewart, Sina Zargaran, Omnia Elebyary, Chunxiang Sun, Michael Glogauer, Yoav Finer

Bibliographic record

VenueActa Biomaterialia · 2025
Typearticle
Languageen
FieldDentistry
TopicDental materials and restorations
Canadian institutionsPrincess Margaret Cancer CentreUniversity of Toronto
FundersOntario Ministry of Research and InnovationCanadian Institutes of Health ResearchCanada Foundation for InnovationOntario Research Foundation
KeywordsMethacrylateAdhesiveFlow cytometryDegradation (telecommunications)Methyl methacrylateInnate immune system

Abstract

fetched live from OpenAlex

Human Neutrophils (HN), white blood cells of the innate immune system, are abundant inhabitants of the oral cavity. It was previously found that these leukocytes can degrade methacrylate resin-based composites (RC), adhesives, monomers, and demineralized dentin. This activity can compromise the tooth-restoration interface, potentially resulting in restoration failure and debonding. Nevertheless, the exact mechanism of this activity is yet to be fully determined. The objectives of this study were to measure cluster of differentiation (CD) marker expression and cell viability of HN when exposed to methacrylate resin-based monomers, degradative byproducts, RC, and adhesives, then to measure and analyze neutrophil-derived enzymes’ degradative activity towards methacrylate resin-based materials. HN’s CD marker expression in the presence of methacrylate resin-based monomers, degradative byproducts, composites, and adhesives was quantified via flow cytometry analysis using a panel of 7 CD markers. HN and neutrophil-derived enzyme degradation of methacrylate resin-based materials was analyzed using ultra performance liquid chromatography and mass spectrometry. Lastly, in silico 3D characterization of the neutrophil-derived enzymes catalytic site was conducted. Results showed increased CD66a among HN exposed to RC and universal-etch adhesive (UE), and upregulated CD11b and CD18 following exposure to UE. Whole HN and neutrophil elastase (NE) degraded 2,2-Bis [4-(2-hydroxy-3-methacryloxypropoxy) phenyl] propane (bisGMA) and urethane dimethacrylate (UDMA) monomers, and photocured RC and UE dental materials(p>0.05). In silico 3D characterization of NE’s active site revealed selective binding configurations to bisGMA and UDMA monomers. These findings suggest that neutrophil-mediated enzymatic degradation of methacrylate resin-based materials may be an important contributing factor to restoration failure and recurrent caries. Neutrophils, innate immune system cells, are found in the gingival sulcus, adjacent to the margins of methacrylate resin-based composites and adhesives. There, neutrophils can combat pathogenic oral bacteria as the body’s first line of defense. This study reveals an in-depth mechanism of the neutrophil-derived enzymatic degradation of methacrylate dental materials, with neutrophil elastase being a key contributor to this potentially harmful activity. This activity, that can occur at the tooth-restoration interface found in the margins of the restorations, can contribute to premature failure of dental restorations, a multi $B health concern. The new culprits unveiled in this study can be targeted in preventive dental treatment, as well as when developing new dental materials with improved longevity and durability. Neutrophils, innate immune system cells, are found in the gingival sulcus, adjacent to the margins of methacrylate resin-based composites and adhesives. There, neutrophils can combat pathogenic oral bacteria as the body’s first line of defense. This study reveals an in-depth mechanism of the neutrophil-derived enzymatic degradation of methacrylate dental materials, with neutrophil elastase being a key contributor to this potentially harmful activity. This activity, that can occur at the tooth-restoration interface found in the margins of the restorations, can contribute to premature failure of dental restorations, a multi $B health concern. The new culprits unveiled in this study can be targeted in preventive dental treatment, as well as when developing new dental materials with improved longevity and durability.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.094
Threshold uncertainty score0.344

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.257
Teacher spread0.241 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2025
Admission routes2
Has abstractyes

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