Can New Remineralizing Agents Serve as Fluoride Alternatives in Caries Prevention? A Scoping Review
Abstract
1. Introduction
2. Materials and Methods
2.1. Review Objectives
2.2. Eligibility Criteria
2.2.1. Inclusion Criteria
- Population: A healthy population (no general disease) with initial stages of dental caries.
- Interventions: Studies involving interventions with definite enamel remineralizing agents: amorphous calcium phosphate (ACP), polyphosphate systems, STMP, functionalized β-tricalcium phosphate, calcium sodium phosphosilicate (CSP), casein phosphopeptide–amorphous calcium phosphate (CPP-ACP), self-assembling polypeptide, P11-4, nano-hydroxyapatite, and fluoride.
- Outcomes: Laboratory studies: definite dg criteria: remineralization of enamel-scanning electron microscopy, spectroscopy, microhardness test, light microscopy, profilometry, transverse microhardness microradiography, integrated mineral loss, light microscopy, photothermal radiometry, and microcomputed tomography (MCT); Clinical studies: RCT, CONSORT document, and trial registration.
- Study design: Randomized controlled trials (RCT, CONSORT document, trial registration), in vitro, in vivo, and in situ studies.
- Language: English only.
- Period of search: From the end of August to 28 October 2024.
- Publication type: Peer-reviewed studies only.
2.2.2. Exclusion Criteria
- Unhealthy population.
- Studies reported the effect affecting dentine.
- Studies not reporting the isolated effect of a definite enamel-remineralizing effect. Also, studies that do not use a definite enamel-remineralizing effect.
- The outcomes were measured without the use of the outcome criteria.
- Studies not published in English.
- Repetitive data.
2.3. Information Sources and Search Strategy
2.4. Study Selection, Data Extraction, and Synthesis
3. Results
The Name of the Agent | Remin/Demin | Biofilm | Adverse Effect | Commercial Product |
---|---|---|---|---|
Fluoride | Remin↑/Demin↓ A high fluoride dose results in surface-zone remineralization and only prevents fuller and homogenous remineralization of the lesion [5]. Incorporation of fluoride into the tooth surface is at a very low level with no “hardening” of the tooth [19]. Those remineralizing properties of fluorides and their mechanisms of inhibiting demineralization have not yet been fully understood [19]. | Reduces saccharolytic organisms and inhibits pathways of sugar fermentation [20,21]; also, it prevents demineralization without affecting biofilm composition and growth inhibits various bacterial enzymes that are necessary for cell growth, sugar transport, and energy metabolism (e.g., enolase, F-ATPase, sulfatase, catalase, phosphatases, and phosphoglucomutase) [21]. | Fluorosis | A wide range of commercial products available |
Amorphous calcium phosphate | Insufficiently remineralized sub-surface lesions with dental calculus depositions on teeth [7,22]. | No studies are available. | No | EnamelonTM toothpaste (https://www.enamelon.com, accessed on the 30 September 2024) |
Sodium trimetaphosphate (STMP) | Strongly binds to phosphate on enamel (which blocks the release of calcium and phosphate from the crystal) and leads to the formation of a layer on the enamel surface that limits acid ion diffusion, but calcium and phosphate diffusion is not affected; was able to minimize mineral loss even in the presence of low F concentrations [7,22]. | ↓The number of Str. mutans cells, and ↓biofilm metabolism (without F) [23]. Also, STMP+F led to the formation of a less compact biofilm [24,25]. STMP alone had a reducing effect, mainly on the metabolism and the extracellular matrix components of the biofilms [26]. | No | Oral-B Pro Expert toothpaste (https://www.oralb.co.uk; https://oralb.com/en-us, accessed on the 30 September 2024) |
Functionalized β-tricalcium phosphate (f β-TCP) | Boost F-ion activity on the tooth surface, with remineralization driven mostly by salivary Ca2+ and PO43− ions [7,22]. f-TCP creates barriers to prevent interactions between fluoride and calcium, delivering minerals and fluoride to the teeth’ surface [21]. The minerals produced by the combination of fluoride and fTCP have greater acid resistance potential than F, β-TCP, and f-TCP alone [27]. | f-TCP, in addition to AgNO3 and NaF, reduced the damage of dentine caries caused by cariogenic biofilm [28]. | No | 3M™ Clinpro™ 5000 1.1% Sodium Fluoride (https://www.solventum.com/en-us/home/f/b00005767/, accessed on the 30 September 2024) 3M™ Clinpro™ XT Varnish Durable Fluoride-Releasing Coating 3M (https://www.3m.com/3M/sl_SI/p/d/v000180763, accessed on the 30 September 2024) |
Calcium sodium phosphosilicate (Bioglass) | When it interacts with saliva, it releases Na+, Ca2+, and PO43− ions and deposits a crystalline hydroxycarbonate apatite layer like the structure of the natural tooth minerals [7,22]. Remin↑/Demine↓ [28] | It has demonstrated antimicrobial effects against various microbial genera, including S. gordonii, V. parvula, P. aeruginosa, and MRSA (methicillin-resistant, Staphylococcus aureus) [29]. | No | NovaMin toothpaste, Sensodyne (https://www.sensodyne.com/en-ca/products/repair-and-protect-original, accessed on the 30 September 2024) Oravive Revitalizing Toothpaste With Novamin, GSK (https://www.instacart.com/products/22049256-oravive-toothpaste-revitalizing-classic-regular-strength-double-mint-4-00-oz, accessed on the 30 September 2024) |
Casein phosphopeptide–amorphous calcium phosphate (CPP-ACP) | ↑Remin of subsurface lesions, supplying a high concentration of calcium and phosphate ions [28]. | ↓ The number of Str. Mutans at a higher rate than fluoride toothpaste alone [30,31,32]. | It could not be used in people with an allergy to lactose. | MI Paste cremes, Recaldent, Trident White sugar-free gum, MI Paste One toothpaste MI Varnish, GC (https://www.gc.dental/europe/en/products, accessed on the 30 September 2024) (https://www.gc.dental/america/products, accessed on the 30 September 2024) |
Self-assembling peptides P11-4 | Forms a 3D scaffold in carious lesions and promotes the new formation of hydroxyapatite crystals [33]. | The self-assembling peptide P11-4 exhibited an inhibitory influence on S. Mutans, which may lead to changes in the formation of cariogenic bacteria biofilm [34]. | No | Curodont Repair, Straumann (https://professional.vvardis.com/product/curodont-repair, accessed on the 30 September 2024) (https://professional.vvardis.us/products/#repair, accessed on the 30 September 2024) |
Nano-hydroxyapatite | It induces remineralization of initial caries lesions by filling micropores in demineralized tooth surfaces, where it acts as a crystal nucleus and promotes crystal deposition and growth by continuously attracting large amounts of calcium and phosphate ions from the surrounding remineralization solution [5]. | HAP reduces the initial plaque formation on enamel surfaces [19]. It acts as an acid buffer and reservoir for calcium and phosphate ions in plaque, leading to significant reduction and inhibition of plaque formation without killing bacteria [19]. The high potential of HAP to adsorb to bacterial cell walls facilitates an antibiofilm effect by inducing coaggregation of bacteria within the HAP particles, aiding biofilm removal from the tooth surfaces, and hindering oral biofilm formation [5]. | No | Pro-Mineralizer Toothpaste, Great Oral Health; Kinder Karex Zahnpasta, Dr. Kurt Wolff GmbH and Co. KG, Bielefeld (https://www.karex.com/en-de/products/kinder-karex-toothpaste, accessed on the 30 September 2024) APAGARD® M-plus toothpaste (https://www.sangi-eu.com/en/apagard-m-plus/mpc125n, accessed on the 30 September 2024) (https://www.sangi-co.com/en/products/apagard_mplus/index.html, accessed on the 30 September 2024) Desensin® oral rinse, DENTAID technologies (https://www.dentaid.com/en/countries, accessed on the 30 September 2024) |
4. Discussion
4.1. Amorphous Calcium Phosphate
4.2. Polyphosphate Systems (Sodium Trimetaphosphate, Calcium Glycerophosphate, Sodium Hexametaphosphate)
4.3. Functionalized β-Tricalcium Phosphate
4.4. Calcium Sodium Phosphosilicate
4.5. Casein Phosphopeptide–Amorphous Calcium Phosphate (CPP-ACP)
4.6. Self-Assembling Polypeptide
4.7. Nano-Hydroxyapatite (nHA, Crystalline)
4.8. Main Findings and Limitations
4.8.1. Main Findings
4.8.2. Limitations of Evidence Included
Study Design and Sample Size
Methodology
Lack of Standardized Outcomes
Bias and Confounding Factors
4.8.3. Limitations of the Review Processes
4.8.4. Future Directions
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Gudkina, J.; Amaechi, B.T.; Abrams, S.H.; Brinkmane, A. Can New Remineralizing Agents Serve as Fluoride Alternatives in Caries Prevention? A Scoping Review. Oral 2025, 5, 47. https://doi.org/10.3390/oral5030047
Gudkina J, Amaechi BT, Abrams SH, Brinkmane A. Can New Remineralizing Agents Serve as Fluoride Alternatives in Caries Prevention? A Scoping Review. Oral. 2025; 5(3):47. https://doi.org/10.3390/oral5030047
Chicago/Turabian StyleGudkina, Jekaterina, Bennett T. Amaechi, Stephen H. Abrams, and Anda Brinkmane. 2025. "Can New Remineralizing Agents Serve as Fluoride Alternatives in Caries Prevention? A Scoping Review" Oral 5, no. 3: 47. https://doi.org/10.3390/oral5030047
APA StyleGudkina, J., Amaechi, B. T., Abrams, S. H., & Brinkmane, A. (2025). Can New Remineralizing Agents Serve as Fluoride Alternatives in Caries Prevention? A Scoping Review. Oral, 5(3), 47. https://doi.org/10.3390/oral5030047