Cavities could be prevented by a gel that restores tooth enamel

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Startup Company website:

The researchers envision the treatment being available in two forms: a daily-use toothpaste or a professional gel applied by dentists, similar to nail varnish. According to the team, keratin-based enamel repair products could be accessible to the public within two to three years.

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The open accèss research paper:

Biomimetic supramolecular protein matrix restores structure and properties of human dental enamel

Tooth enamel is characterised by an intricate hierarchical organization of apatite nanocrystals that bestows high stiffness, hardness, and fracture toughness. However, enamel does not possess the ability to regenerate, and achieving the artificial restoration of its microstructure and mechanical properties in clinical settings has proven challenging. To tackle this issue, we engineer a tuneable and resilient supramolecular matrix based on elastin-like recombinamers (ELRs) that imitates the structure and function of the enamel-developing matrix. When applied as a coating on the surface of teeth exhibiting different levels of erosion, the matrix is stable and can trigger epitaxial growth of apatite nanocrystals, recreating the microarchitecture of the different anatomical regions of enamel and restoring the mechanical properties. The study demonstrates the translational potential of our mineralising technology for treating loss of enamel in clinical settings such as the treatment of enamel erosion and dental hypersensitivity.

https://www.nature.com/articles/s41467-025-64982-y

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GPT5 Analysis of the paper:

Structured Report on: “Biomimetic supramolecular protein matrix restores structure and properties of human dental enamel” (Nature Communications, 2025)

1) Executive Summary (Study, Methods, Main Findings)

This paper reports a biomimetic coating made from elastin-like recombinamers (ELRs) formulated with Ca²⁺ and a crosslinker to emulate the β-rich fibrillar protein matrix that guides natural enamel mineralization. When drop-cast onto human teeth with varying degrees of erosion (including down to exposed dentin) ex vivo, the ELR matrix nucleates and supports epitaxial growth of apatite, recreating enamel microarchitecture (aprismatic and prismatic features) and restoring multiple mechanical properties (stiffness, hardness, fracture toughness, wear resistance, friction) toward native enamel values. Layers up to ~10 µm are reported. The approach is tested after common “insults” (prolonged brushing, simulated chewing & grinding, acid exposure) and in natural human saliva; biocompatibility is assessed on mammalian cells. Data and source files are made openly available; a peer-review file is posted.

2) Journal & Publication Quality

  • Peer review & indexing. Nature Communications is a fully open-access, peer-reviewed Nature Portfolio journal indexed in Web of Science, PubMed/PMC, Scopus, DOAJ and others.
  • Impact & reputation. 2024 Journal Impact Factor 15.7; 5-year JIF 17.2; high Eigenfactor and SJR metrics are reported on the journal’s metrics page.
  • Transparency. Nature Portfolio now provides transparent peer-review files for new articles; this paper indicates a peer-review file is available.

Assessment: High-reputation, rigorously reviewed venue with strong indexing and open data norms.

3) Study Design & Methods

  • Type. Experimental ex vivo materials/biomineralization study on extracted human teeth; not an animal or human clinical trial.
  • Specimens & ethics. Human molar teeth extracted for clinical reasons; ethics approval from University of Nottingham (FMHS 313-0721); informed consent obtained.
  • Coating formulation & application. Typical protocol: 5% (w/v) ELR in DMF/DMSO (9:1) with 1.5 mM Ca²⁺ and 0.56% v/v hexamethylene diisocyanate (HDI) drop-cast onto acid-etched enamel/dentin and dried/crosslinked for ~1.5 h at 25 °C under controlled humidity; an ethanol/water (85/15) + 1.5% glutaraldehyde alternative is also described.
  • Remineralization conditions. Subsequent exposure to solutions supersaturated for fluorapatite; additional tests include remineralization in natural human saliva from three adult donors (20–40 yrs) with a defined collection/replenishment protocol.
  • Characterization toolkit. SEM/TEM, WAXS/SAXS, FTIR, XRD, FIB-TEM (lamellae from decussated zones), AFM, nanoindentation, fracture toughness (indentation-crack method), tribology (coefficient of friction), wear (Rub&Roll apparatus), brushing abrasion, acid challenge.
  • Biocompatibility. MTS and Live/Dead assays on NIH-3T3, human MSCs, and HUVECs using ELR coatings prepared in ethanol/water with glutaraldehyde.
  • Data availability. Source data for all main and supplementary figures are open (institutional DOI) and stated as provided with the paper.
  • Preregistration. Not applicable (no clinical RCT); no preregistration indicated.

Assessment: Methods are explicit and, for a materials/biomaterials paper, sufficiently detailed to be reproducible(including solvents, concentrations, crosslinkers, times, and environments). Safety/translational steps are preliminary (ex vivo + in vitro).

4) Sample Size & Power

  • Mechanical/tribological tests report specific n’s per assay (e.g., fracture toughness n = 3, wear/height loss n = 8 enamel and n = 8 dentin; brushing and acid-attack datasets show many indents per group with multiple independent experiments). No formal power calculation is reported (typical for this domain), but effect magnitudes are large and consistent across modalities.

5) Data & Statistical Analysis

  • Accuracy/consistency. Figures present native vs eroded vs remineralized comparisons across properties; conditions are labeled; microstructural and crystallographic evidence (epitaxy, c-axis) align with mechanical trends.
  • Statistics. Mean Âą SD; two-sided one-way ANOVA with Tukey for ≥3 groups; two-tailed Student’s t-tests for pairwise comparisons; p < 0.05 threshold stated.

Assessment: Statistical approach is standard and appropriate for materials testing with multiple groups. Multiple independent experiments and site-matched measures (nanoindentation arrays) help robustness.

6) Results & Conclusions

  • Microstructure. ELR forms Ca²⁺-mediated β-rich fibrils (15–40 nm) with cross-β signatures by WAXS/FTIR; on enamel/dentin these scaffolds guide apatite nucleation and epitaxial extension along the c-axis, recreating aprismatic and prismatic architectures.
  • Mechanical restoration. After treatment, Young’s modulus, hardness, and apparent fracture toughnessapproach native enamel; performance persists after 15–60 min brushing, chewing/grinding (Rub&Roll ~806,400 cycles ≈ 3.5 years), and acid challenges (15 min to 2 days).
  • Wear & friction. Remineralized enamel/dentin show improved wear and reduced height loss vs. eroded controls; friction metrics trend toward native enamel.
  • Saliva robustness. Remineralization achieved using natural human saliva over 14 days showed restored nanoindentation properties and microstructure by SEM.
  • Cytocompatibility. ELR coatings (ethanol/water + glutaraldehyde variant) support viability of fibroblasts, MSCs, and HUVECs in vitro.

Conclusion support: Claims are well supported for ex vivo tooth specimens and in vitro cells. The authors appropriately highlight “translational potential” rather than clinical efficacy.

7) References & Author Credibility

  • References. Extensive, current citations on amelogenin-guided mineralization, enamel structure, and biomimetic approaches; balance of supportive and comparative literature.
  • Author expertise. Multidisciplinary team (biomaterials, dentistry, tribology, structural analysis) from recognized institutions; multiple enamel/mineralization experts listed. (Affiliations and contributions detailed in the paper.)
  • Conflicts/funding. Funded by ERC (PoC), EPSRC/MRC/NIHR, AO Foundation, Innovate UK, etc. Two authors (first and senior) co-founded Mintech-Bio Ltd to translate the technology; others declare no conflicts. This is a material COI relevant to translational claims.

8) Context & Knowledge Contribution

  • Position in field. Prior enamel-mimetic methods either rebuild limited architecture (aprismatic or partial prismatic) or rely on toxic reagents and long application times. This ELR system offers one-pot, short, clinically plausible application, controls fibril order and nucleation, and reconstructs both aprismatic and prismatic structures with functional property recovery.
  • How it extends knowledge. Demonstrates epitaxial growth from native crystals into a continuous, hierarchical layer with multi-property restoration and durability under realistic oral insults—an advance over peptide films or non-physiological nanocomposites.
  • Generalizability. Strong for ex vivo human teeth; however, in-mouth variables (salivary flow/chemistry, pellicle/biofilm, pH cycling, temperature, dietary acids, tongue forces, patient behavior) remain untested in vivo. Safety and practicality of solvents and crosslinkers (DMF/DMSO + HDI; ethanol/water + glutaraldehyde) require careful clinical-grade reformulation and toxicology.

9) Strengths, Weaknesses, Overall Assessment

Strengths

  • High-quality venue with open data and posted peer-review file.
  • Clear mechanistic rationale (β-rich fibrils → guided apatite epitaxy), validated by multi-scale structural methods (WAXS/FTIR/TEM/FIB).
  • Functional breadth: stiffness, hardness, toughness, friction, wear, brushing, acid resistance, and saliva mineralization—all trending toward native enamel.
  • Reproducible protocols with concentrations, times, and environments specified; data deposited.

Weaknesses / Caveats

  • No in vivo/clinical testing ; all tooth results are ex vivo .
  • Translational chemistry: DMF/DMSO and HDI crosslinker (and the glutaraldehyde variant) are not immediately clinic-ready; additional toxicology, formulation changes, or curing strategies are needed for safe chair-side use. (Methods explicitly use these reagents.)
  • Sample sizes modest in some assays (e.g., fracture toughness n=3); while effects are large, formal power analysesare not reported.
  • Conflict of interest (spin-out company by first/senior authors) requires independent replication.

Overall Reliability & Impact

Reliability: High for an ex vivo materials study—comprehensive characterization, appropriate statistics, and open data enhance trust. Translational claims are promising but preclinical.

Impact: Substantial within biomimetic enamel regeneration—restoring both architecture and functional properties with one coating is a meaningful step forward. The next critical milestones are biocompatible clinical-grade formulations, in vivo performance in animals/humans, and durability under real oral conditions (months–years).

10) Key Details & Numbers (for quick reference)

  • Layer thickness: reported up to ~10 Âľm .
  • Brushing durability: properties maintained after 15–60 min continuous brushing.
  • Wear simulation: Rub&Roll ~806,400 cycles (~3.5 years equivalent).
  • Acid challenge: 0.1 M acid for 15 min and 2 days; functional properties comparatively preserved.
  • Saliva study: 3 donors (20–40 yrs), 12 h/day saliva exposure for 14 days with replenishment schedule.
  • Biocompatibility: MTS & Live/Dead on NIH-3T3, human MSCs, HUVECs.

11) Bottom Line

A rigorous ex vivo demonstration that a biomimetic ELR matrix can epitaxially regrow enamel-like mineral on human teeth and restore multiple mechanical functions. Excellent basic and translational science; clinical translation will hinge on reformulation for safety, regulatory-grade toxicology, and controlled in vivo trials.

Sources: the article PDF and methods/results figures; Nature Communications journal information and metrics.