Human Enamel Rebuilt: Inside the Technology That Could Transform Dentistry

Leon Wirz
2 hours ago
5 min read

Published in Nature Communications (2025), University of Nottingham & International Research Partners

Introduction

Tooth enamel is the hardest material in the human body, yet paradoxically, it is also one of the most vulnerable once damaged. Unlike bone, enamel cannot regenerate. When it erodes due to acids, grinding, or daily mechanical wear, the loss is permanent. The consequences range from sensitivity and pain to cavities, infections, and, in severe cases, tooth loss. On a global scale, dental diseases represent an economic burden of more than USD 500 billion every year, reflecting both treatment costs and productivity loss.

Now, researchers from the University of Nottingham report a potential paradigm shift: a biomimetic protein gel capable of regrowing enamel-like tissue on human teeth. Published in Nature Communications (2025), the study demonstrates how a supramolecular protein matrix can recreate the microstructure and mechanical strength of natural enamel, raising the possibility of a future regenerative therapy.

The Tooth: What You Need to Know

A human tooth consists of three major layers: the enamel, the dentine, and the pulp. Enamel, the outermost layer, is composed almost entirely of tightly packed hydroxyapatite crystals. Its remarkable hardness depends on a highly organised architecture: aligned nanocrystals arranged into prisms and inter-prismatic patterns. Beneath enamel lies dentine, a collagen-rich material that is softer, contains tubules, and is sensitive when exposed.

Crucially, enamel cannot regrow. The cells that create enamel during development (ameloblasts) disappear once the tooth erupts. This is why damage to enamel must currently be treated with artificial materials like composites, ceramics, or crowns. None of these fully recreate the structure, durability, or long-term behaviour of natural enamel.

The Nottingham study aims to bridge exactly this gap: not by patching the tooth, but by restoring the natural mineral architecture itself.

The Core Discovery

The researchers developed a supramolecular protein matrix made from engineered elastin-like recombinamers (ELRs). These proteins self-assemble into fibrillar networks that imitate the enamel-forming scaffold present during early tooth development. When the matrix is applied to damaged enamel (or even completely exposed dentine) it acts as a blueprint, triggering the organised growth of apatite nanocrystals.

The key breakthrough is that the regenerated mineral layer:

grows epitaxially (i.e., crystals extend directly from the underlying native enamel),
reproduces the correct hierarchical architecture,
and restores mechanical properties close to natural enamel.

This represents a substantial improvement over previous biomimetic approaches, which typically produced disorganised mineral layers or lacked sufficient mechanical strength.

How the Study Was Conducted

The research was performed ex vivo on extracted human molars. The enamel was first eroded using phosphoric acid to mimic real-world clinical conditions. The team then applied the ELR solution, which formed a thin, uniform coating within minutes.

Samples were incubated either in mineralising solutions supersaturated with fluorapatite or in artificial saliva. Over the course of several days, the ELR matrix directed the nucleation, alignment, and growth of enamel-like crystals. The authors verified this using advanced imaging techniques such as SEM, TEM, confocal microscopy, and X-ray scattering.

To evaluate functionality, the regenerated enamel underwent mechanical testing:

indentation to measure stiffness and hardness,
friction testing to examine wear resistance,
fracture analysis,
and simulations of brushing, chewing, and acid exposure.

The researchers also tested mineralisation in natural human saliva, introducing variability that more closely reflects conditions in the mouth.

Key Findings

The study provides strong evidence that the ELR matrix is capable of restoring both structure and function of enamel across multiple anatomical regions.

Reconstruction of Enamel Architecture

The regenerated layers faithfully reproduced aprismatic enamel on the surface, the complex prism–interprism organisation of deeper enamel regions, and even enamel-like mineral on exposed dentine. High-resolution electron microscopy showed that new apatite crystals extended directly from the existing enamel or dentine structures, aligning along their natural c-axis.

Mechanical Restoration

Acid-etched enamel displayed significant loss of stiffness and hardness. After remineralisation:

Young’s modulus increased from ~37 GPa back to ~76–81 GPa,
Hardness rose to ~3.1–3.4 GPa, closely matching native enamel.

Wear resistance, fracture toughness, and coefficient of friction returned to levels comparable to (and in some tests even exceeding) natural enamel.

Robustness Under Oral-Mimicking Conditions

The regenerated enamel layer maintained integrity during simulations of extended brushing, high mechanical loads, and short- and long-term acid exposure. Importantly, mineralisation in natural human saliva produced similar structural and mechanical outcomes, suggesting resilience in biologically complex environments.

Limitations of the Study

While the findings are highly promising, several important limitations must be acknowledged:

All experiments were conducted ex vivo, outside the living oral environment.
The regenerated enamel layers were relatively thin (2–10 µm), which may limit their durability in long-term real-world use.
Oral microbiome interactions, salivary variability, and long-term degradation of the protein matrix require further investigation.
Clinical translation will depend on controlled trials, safety evaluations, and regulatory approval.

Even so, the level of structural regeneration achieved in this study has not been previously reported.

Relevance for Switzerland

Switzerland has some of the highest dental care costs in Europe, driven by limited dental insurance coverage and high out-of-pocket spending. Enamel erosion, hypersensitivity, and early-stage tooth wear are common presentations in both young and older adults.

A therapy capable of non-invasive enamel restoration could have several impacts:

reducing the need for drilling, fillings, and crowns,
lowering long-term dental expenditures for individuals,
influencing insurance products and reimbursement structures,
and creating opportunities for Swiss dental-material companies to engage in translational partnerships.

For a healthcare system that emphasises prevention and high-quality care, enamel regeneration represents a potentially disruptive innovation.

Potential Impacts of a Successful Therapy

If validated in clinical settings, the technology could shift restorative dentistry toward biological regeneration rather than mechanical repair. Patients with early enamel erosion or sensitivity could receive quick, minimally invasive treatments. Dentists might reduce reliance on artificial materials and instead stabilise natural tooth structures.

On a systemic level, insurers could benefit from lower-cost preventive interventions, potentially decreasing expenditures related to crowns, large fillings, and eventual prosthetic work. The therapy may also open the door to consumer-grade preventive products aimed at early-stage enamel wear.

Risks

Potential risks and uncertainties remain. The long-term behaviour of regenerated enamel in the complex oral environment is unknown. Individual variations in saliva composition, pH, and microbiota could affect treatment outcomes. Hypersensitivity or allergic reactions to matrix components, while unlikely, must be evaluated. Additionally, over-reliance on a new biomaterial before full clinical validation could lead to premature adoption.

Overall Assessment

This study represents a scientifically robust and methodologically rigorous step forward in enamel regeneration research. By demonstrating the ability to reproduce both the microstructure and mechanical behaviour of enamel, the Nottingham team has achieved a milestone that previous technologies fell short of. Although the findings are preclinical and require significant additional work, the translational potential is clear.

What Comes Next

Future steps include:

In vivo studies to evaluate long-term stability and performance in the living mouth,
Pilot human trials, particularly for enamel erosion and hypersensitivity,
optimisation of coating protocols for dentists,
assessment of long-term safety and biodegradation,
regulatory approval pathways,
and modelling of economic impact for insurers and healthcare systems.

Depending on clinical outcomes, this technology may form the basis of the first truly regenerative dental treatment for enamel loss.

Reference

Hasan A, Chuvilin A, Van Teijlingen A, Rouco H, Parmenter C, Venturi F, Fay M, Greco G, Pugno NM, Ruben J, Edwards-Gayle CJC, Myers B, Dreveny I, Cowieson N, Winter A, Gamea S, Walboomers XF, Hussain T, Rodríguez-Cabello JC, Rawson F, Tuttle T, Elsharkawy S, Banerjee A, Habelitz S, Mata A. Biomimetic supramolecular protein matrix restores structure and properties of human dental enamel. Nat Commun. 2025 Nov Link