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20 pages, 2717 KB  
Article
Biomimetic Strategies for Subsurface Enamel Remineralization: Depth-Dependent Effects of Biomimetic Agents Compared with Fluoride
by İlknur Akay Dede and Suat Özcan
Biomimetics 2026, 11(8), 525; https://doi.org/10.3390/biomimetics11080525 - 24 Jul 2026
Viewed by 168
Abstract
This study compared the remineralization potential of three commercially available fluoride-free biomimetic formulations containing nanohydroxyapatite (nHAp), casein phosphopeptide–amorphous calcium phosphate (CPP-ACP), and bioactive glass (BAG) with a conventional 1450 ppm fluoride-containing dentifrice using cross-sectional microhardness and SEM analyses. Seventy extracted human mandibular molars [...] Read more.
This study compared the remineralization potential of three commercially available fluoride-free biomimetic formulations containing nanohydroxyapatite (nHAp), casein phosphopeptide–amorphous calcium phosphate (CPP-ACP), and bioactive glass (BAG) with a conventional 1450 ppm fluoride-containing dentifrice using cross-sectional microhardness and SEM analyses. Seventy extracted human mandibular molars were randomly allocated to five groups (n = 14). Artificial carious lesions were created by 72 h of demineralization followed by a 14-day pH-cycling regimen with twice-daily treatment applications. Cross-sectional microhardness was measured at depths of 30, 50, 100, and 150 µm, and SEM was used to evaluate morphological changes. Data were analyzed using one-way ANOVA with appropriate post hoc tests (Tukey’s HSD or Tamhane’s T2, depending on variance homogeneity) and repeated-measures ANOVA to assess depth-dependent differences among groups (α = 0.05). Demineralization significantly reduced microhardness at all depths (p < 0.05). At 30 µm, the nHAp, CPP-ACP, and fluoride formulations showed similar remineralization, whereas the BAG-containing formulation exhibited lower superficial recovery. At 100–150 µm, the nHAp formulation demonstrated the greatest recovery, followed by the CPP-ACP and BAG formulations, while the fluoride dentifrice showed progressively lower recovery. A significant depth-by-group interaction confirmed distinct depth-dependent remineralization profiles. Within the limitations of this in vitro study, all tested formulations promoted enamel remineralization but exhibited different depth-dependent recovery patterns. Full article
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17 pages, 19305 KB  
Article
Remineralization of Artificial Caries-like Lesions in Permanent Enamel by MI Paste One: Comparative Physicochemical Outcomes and In Vitro Resistance to Secondary Demineralization
by Najla F. Alsayari, Sarah S. Al-Angari, Latifa A. Alhowaish, Abdulaziz S. Alangari, Raman Bedi, Ayman M. Sulimany and Maha A. Alsarheed
J. Funct. Biomater. 2026, 17(7), 333; https://doi.org/10.3390/jfb17070333 - 9 Jul 2026
Viewed by 585
Abstract
Background: Patients with White spot lesions (WSLs) are seeking minimally invasive remineralizing treatment. While fluoride is the gold standard of non-invasive caries therapy, its remineralizing impact is predominantly superficial. MI Paste One (MIP-1) combines casein phosphopeptide–amorphous calcium phosphate (CPP–ACP) with 1100 ppm fluoride. [...] Read more.
Background: Patients with White spot lesions (WSLs) are seeking minimally invasive remineralizing treatment. While fluoride is the gold standard of non-invasive caries therapy, its remineralizing impact is predominantly superficial. MI Paste One (MIP-1) combines casein phosphopeptide–amorphous calcium phosphate (CPP–ACP) with 1100 ppm fluoride. This in vitro study aimed to assess the effect of MIP-1 compared with other agents. Methods: Enamel slabs were demineralized to create a caries-like lesion and randomized into five groups (n = 10): G1, WSL/artificial saliva (AS) (negative control); G2, deionized water brushing; G3, fluoridated toothpaste brushing; G4, MIP-1 brushing; G5, topical MI Paste application. Color change (ΔE), gloss (GU), microhardness (VHN), roughness (Ra), and surface topography (SEM) were assessed at four time points: baseline, first demineralization, treatment, and second demineralization. Results: All active agents improved microhardness after treatment. After secondary demineralization, G4 achieved the highest hardness, significantly superior to G3 (p = 0.016). G5 occupied a statistically intermediate position. CPP–ACP-containing agents (G4, G5) achieved color improvement that was significantly superior to controls. Conclusions: MIP-1 outperformed fluoride toothpaste in resisting secondary demineralization of permanent enamel WSLs. CPP–ACP made a measurable independent contribution to demineralization resistance in permanent enamel. These findings highlight the need for further clinical investigation of MIP-1. Full article
(This article belongs to the Section Dental Biomaterials)
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24 pages, 3895 KB  
Review
Enamel Remineralizing Agents: State of the Art
by Elizabeta Gjorgievska, Marija Stevanovic, Aleksandar Dimkov and John W. Nicholson
Materials 2026, 19(12), 2550; https://doi.org/10.3390/ma19122550 - 12 Jun 2026
Viewed by 564
Abstract
Dental caries remains the most prevalent chronic disease worldwide, yet early enamel lesions are reversible if managed with appropriate remineralizing agents. This narrative review synthesizes current evidence on remineralizing agents, their mechanisms of action, and clinical applications, with a focus on dental materials [...] Read more.
Dental caries remains the most prevalent chronic disease worldwide, yet early enamel lesions are reversible if managed with appropriate remineralizing agents. This narrative review synthesizes current evidence on remineralizing agents, their mechanisms of action, and clinical applications, with a focus on dental materials used in preventive and minimally invasive dentistry. Traditional fluoride-based approaches enhance remineralization through fluorapatite formation; however, their effectiveness is limited when calcium and phosphate bioavailability is insufficient. Biomimetic agents, including casein phosphopeptide–amorphous calcium phosphate (CPP-ACP), bioactive glasses, tricalcium phosphate, and nano-hydroxyapatite, provide these bioavailable ions and demonstrate superior performance under challenging clinical conditions. Emerging therapies such as probiotics, photodynamic therapy, and laser-assisted mineralization show promise but require further clinical validation. Based on the primary mechanism of action, an original classification of remineralizing agents is proposed, grouping them into fluoride-based agents, calcium-phosphate systems, nanotechnology-based systems, biofilm modifiers, biomimetic and emerging systems, and adjunctive antimicrobial therapies. The review concludes that bioavailable calcium represents a critical limiting factor in remineralization under certain conditions, and that combination protocols incorporating multiple remineralizing agents, tailored to individual patient risk profiles, achieve superior outcomes compared to single-agent approaches. Clinicians are encouraged to adopt minimally invasive, patient-tailored remineralization strategies that arrest lesions before cavitation, preserving natural tooth structure and reducing the lifelong restorative burden. Full article
(This article belongs to the Special Issue Recent Research in Restorative Dental Materials (2nd Edition))
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13 pages, 688 KB  
Article
Acidic pH of Commercial Energy Gels, Potential Dental Risk, and the Neutralizing Effect of Casein Phosphopeptide–Amorphous Calcium Phosphate
by María Mónica Beti, Lautaro Alaniz, Matías Alaniz, Verónica García-Sanz, Juan Ignacio Aura-Tormos, Ismael Galancho, Andrea Bono and Vanessa Paredes-Gallardo
Appl. Sci. 2026, 16(8), 3790; https://doi.org/10.3390/app16083790 - 13 Apr 2026
Viewed by 703
Abstract
Energy gels are widely used by athletes to maintain performance during endurance activities; however, their acidic composition may pose a risk to dental health. This study aimed to evaluate the pH of four commercial energy gels at different dilutions with artificial saliva and [...] Read more.
Energy gels are widely used by athletes to maintain performance during endurance activities; however, their acidic composition may pose a risk to dental health. This study aimed to evaluate the pH of four commercial energy gels at different dilutions with artificial saliva and to assess the potential neutralizing effect of casein phosphopeptide–amorphous calcium phosphate (CPP–ACP). An in vitro experimental design was conducted using four commercial gels (FullGas Hydrogel, ENA Energy Gel, UltraTech Gel, and Maverick Race Gel). Serial dilutions with artificial saliva (1:2, 1:5, 1:7, and 1:10) were prepared, and pH was measured using indicator strips at 0, 15, and 30 min at 37 °C. The effect of CPP-ACP was evaluated in the 1:2 dilution. Undiluted gels showed highly acidic pH values ranging from 2.0 to 3.0. Dilutions of 1:2 and 1:5 remained significantly more acidic than artificial saliva (p < 0.001). From 1:7 dilution onward, pH values increased and approached salivary levels (approximately 7.0), with no significant differences compared with artificial saliva. The addition of CPP-ACP significantly increased pH in the 1:2 dilution (p < 0.05), although the effect was limited in more diluted conditions. These findings suggest that commercial energy gels may represent a source of acidic exposure under in vitro conditions, which could be relevant for dental health. Adequate dilution, particularly ≥1:7, was associated with a reduction in acidity under the experimental conditions tested, although its clinical relevance cannot be directly inferred, while CPP-ACP may provide a limited buffering effect under concentrated exposure conditions. Full article
(This article belongs to the Special Issue Food Security, Nutrition, and Public Health)
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22 pages, 646 KB  
Review
Non-Operative, Micro- and Minimally Invasive Methods for Caries Treatment—A Narrative Review
by Veselina Todorova
J. Clin. Med. 2026, 15(4), 1534; https://doi.org/10.3390/jcm15041534 - 15 Feb 2026
Cited by 2 | Viewed by 2992
Abstract
The management of dental caries has evolved from the traditional mechanical approach of “extension for prevention” to a biologically oriented philosophy centered on preserving natural tooth structures. Minimally invasive dentistry (MID) emphasizes early detection, risk assessment, prevention, and conservative intervention based on the [...] Read more.
The management of dental caries has evolved from the traditional mechanical approach of “extension for prevention” to a biologically oriented philosophy centered on preserving natural tooth structures. Minimally invasive dentistry (MID) emphasizes early detection, risk assessment, prevention, and conservative intervention based on the lesion’s activity and depth. This review outlines current evidence on non-operative, micro-invasive, and minimally invasive strategies, including fluoride therapy, remineralizing agents such as casein phosphopeptide–amorphous calcium phosphate (CPP-ACP), self-assembling peptides that promote biomimetic enamel repair, sealants, and resin infiltration. Minimally invasive operative methods employ advanced technologies for selective tissue removal—chemomechanical systems (Carisolv, Papacarie, Brix3000), sono-and airabrasion, and new-generation polymeric and ceramic burs (SmartBur, Cerabur) designed to preserve sound dentin. Laser photoablation, particularly with erbium lasers (Er:YAG, Er,Cr:YSGG), enables precise cavity preparation with minimal thermal and mechanical stress. These approaches enhance patient comfort, reduce anesthesia requirements, and maintain tooth vitality. Despite limitations related to cost, equipment, and operator sensitivity, MID represents not only a set of refined clinical techniques but also a comprehensive, evidence-based treatment philosophy founded on biological principles, structural preservation, and the promotion of long-term oral health. Full article
(This article belongs to the Special Issue Current Challenges in Clinical Dentistry: 3rd Edition)
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23 pages, 755 KB  
Review
Dental Erosion Management: From Remineralization to Emerging Regenerative Approaches—A Narrative Review
by Ruvienath Daham Weerasinghe Rajapaksa, Yu-Ching Wang, Yong Chen Chin, Kevin Jang, Abdala Abdal-hay, Sašo Ivanovski and Sandleen Feroz
Biomimetics 2026, 11(2), 107; https://doi.org/10.3390/biomimetics11020107 - 3 Feb 2026
Cited by 1 | Viewed by 3160
Abstract
Dental erosion has emerged as a significant modern oral health problem, characterized by the chemical dissolution of tooth structure resulting from frequent exposure to intrinsic or extrinsic acids. With a high global prevalence ranging from 30% to 50% in children and 20% to [...] Read more.
Dental erosion has emerged as a significant modern oral health problem, characterized by the chemical dissolution of tooth structure resulting from frequent exposure to intrinsic or extrinsic acids. With a high global prevalence ranging from 30% to 50% in children and 20% to 40% in adults, its management is a clinical priority to prevent long-term complications like dentine hypersensitivity and functional impairment. This review outlines the multifactorial etiology of erosion, encompassing dietary acids, gastroesophageal reflux, and reduced salivary flow. The historical context of oral care is explored, leading to a discussion on contemporary management strategies centered on remineralization. Fluoride ions play a crucial role by inhibiting demineralization, facilitating the formation of acid-resistant fluorapatite, and exerting antibacterial effects. A major focus is placed on advanced biomimetic, calcium phosphate-based topical agents such as Casein Phosphopeptide–Amorphous Calcium Phosphate (CPP-ACP), functionalized Tricalcium Phosphate (fTCP), and Hydroxyapatite (HAP), which effectively replenish lost minerals. The review further explores innovative methods, such as laser-assisted and electrically enhanced remineralization. Finally, it outlines next-generation regenerative strategies, including self-assembling peptides (P11-4), stem cell therapies, 3D bioprinting, and gene-editing (CRISPR) technologies, which aim to biologically regenerate lost enamel and dentine. The field is rapidly evolving from a preventive to a restorative paradigm, with future directions focusing on biologically based, minimally invasive therapies to fully restore tooth structure and function. Full article
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17 pages, 16432 KB  
Article
Enamel Remineralization Potential of Conventional and Biomimetic Toothpaste Formulations: A Comparative In Vitro Study
by Cristina-Angela Ghiorghe, Ionuţ Tărăboanţă, Sorin Andrian, Galina Pancu, Corneliu Munteanu, Bogdan Istrate, Fabian Cezar Lupu, Claudia Maxim and Ana Simona Barna
Dent. J. 2026, 14(2), 82; https://doi.org/10.3390/dj14020082 - 2 Feb 2026
Cited by 1 | Viewed by 1623
Abstract
Background/Objectives: Dental caries remains one of the most prevalent chronic diseases worldwide, making enamel remineralization a key objective in minimally invasive dentistry. This in vitro study compared the remineralization efficacy of five therapeutic toothpastes containing fluoride, NovaMin, CPP-ACP, nano-hydroxyapatite, arginine, and xylitol. [...] Read more.
Background/Objectives: Dental caries remains one of the most prevalent chronic diseases worldwide, making enamel remineralization a key objective in minimally invasive dentistry. This in vitro study compared the remineralization efficacy of five therapeutic toothpastes containing fluoride, NovaMin, CPP-ACP, nano-hydroxyapatite, arginine, and xylitol. Methods: Sixty enamel specimens were prepared from extracted human posterior teeth and artificially demineralized. Samples were randomly allocated into six groups (n = 10): one negative control (C1) stored in artificial saliva and five treatment groups (P1–P5). A 28-day remineralization protocol with twice-daily applications was performed. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used to assess surface morphology and elemental composition (Ca, P, F, Na, O, Ca/P ratio) at days 1, 14, and 28. Vickers microhardness testing was used to evaluate changes in mechanical properties. Statistical analysis included one-way ANOVA, repeated measures ANOVA, Tukey’s post hoc test, and Kruskal–Wallis where appropriate (α = 0.05). Results: All therapeutic toothpastes produced some increase in mineral content compared to the demineralized control. At day 28, significant intergroup differences were observed for calcium, phosphorus, and fluoride (p < 0.001). The arginine–fluoride formulation (P4) and the NovaMin-based formulation (P3) showed the most consistent increases in Ca and P, with SEM revealing the formation of a continuous, compact surface layer and marked reduction in prismatic porosities. Fluoride-containing toothpastes (P1, P3, P4) showed significant fluoride incorporation (p < 0.001 vs. control). The nano-hydroxyapatite/xylitol prototype (P5) produced a delayed but progressive increase in Ca and P, with partial filling of prismatic spaces. The CPP-ACP-based toothpaste (P2) led to limited changes, with only slight differences vs. control at day 28. Vickers microhardness values increased significantly in groups P1, P3, P4, and P5 (p < 0.05), in agreement with the higher mineral levels found in these samples. Conclusions: Under the present in vitro conditions, toothpastes containing fluoride in combination with NovaMin or arginine, as well as nano-hydroxyapatite/xylitol, demonstrated the highest remineralization potential under the present in vitro conditions, both chemically and mechanically. Xylitol-based formulations without a direct mineral supply showed limited effects. The pH and active composition of the toothpaste strongly influenced enamel remineralization outcomes. Full article
(This article belongs to the Section Preventive Dentistry)
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15 pages, 614 KB  
Review
Oral Manifestations of Sjögren’s Syndrome: Recognition, Management, and Interdisciplinary Care
by Shu-Cheng Liu, Ming-Chi Lu and Malcolm Koo
Medicina 2026, 62(1), 5; https://doi.org/10.3390/medicina62010005 - 19 Dec 2025
Cited by 2 | Viewed by 3077
Abstract
Background and Objectives: Sjögren’s syndrome (SS) causes destructive salivary gland dysfunction with substantial oral morbidity. To synthesize practical, evidence-based approaches for early recognition, initial oral management, and timely referral to dental care. Materials and Methods: Narrative review of English-language literature from [...] Read more.
Background and Objectives: Sjögren’s syndrome (SS) causes destructive salivary gland dysfunction with substantial oral morbidity. To synthesize practical, evidence-based approaches for early recognition, initial oral management, and timely referral to dental care. Materials and Methods: Narrative review of English-language literature from the Web of Science Core Collection and PubMed, prioritizing systematic reviews, randomized trials, and consensus guidelines. Results: Early oral signs include rapid multifocal root and cervical caries, burning sensations, and rising dental treatment needs. Unstimulated whole saliva ≤ 0.1 mL/min supports significant hypofunction and complements the 2016 ACR/EULAR criteria. Preventive care should combine dietary counseling, salivary stimulation, and topical remineralization. Adjuncts include high-fluoride toothpaste, biomimetic hydroxyapatite dentifrices, and casein phosphopeptide–amorphous calcium phosphate (CPP-ACP). However, evidence for fluoride varnish in SS remains mixed. Pharmacologic sialogogues require screening for contraindications. Conclusions: Embedding oral screening, simple salivary metrics, and a structured referral pathway into rheumatology visits can reduce preventable tooth loss and improve comfort, function, and treatment adherence. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases—3rd Edition)
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13 pages, 2269 KB  
Article
The Effect of Different White Spot Lesion Treatments on the Enamel Microhardness—An In Vitro Pilot Study
by Milena Milanović, Miloš Beloica, Zoran Mandinić, Jelena Juloski, Miloš Petrović, Dušan Kosanović, Miloš Todorović, Maja Dimitrijević, Aleksandar Jakovljević, Miloš Vorkapić and Dragan Stanimirović
Dent. J. 2025, 13(11), 496; https://doi.org/10.3390/dj13110496 - 27 Oct 2025
Cited by 1 | Viewed by 1996
Abstract
Background/Objectives: Dental caries, one of the most common oral diseases worldwide, represents a major public health concern. Contemporary dentistry has established several non-invasive approaches and resin infiltration, as a micro-invasive path, in the treatment of white spot lesions (WSLs). This study aimed to [...] Read more.
Background/Objectives: Dental caries, one of the most common oral diseases worldwide, represents a major public health concern. Contemporary dentistry has established several non-invasive approaches and resin infiltration, as a micro-invasive path, in the treatment of white spot lesions (WSLs). This study aimed to evaluate the effect of different WSL treatments on enamel surface microhardness. Materials and Methods: Seventy-five intact human premolars extracted upon orthodontic indication and the demineralizing solution composed of acetic acid, monopotassium phosphate and calcium chloride with pH = 4.4 and exposure time 96 h were used. The samples were randomly divided into five groups (n = 15): I—intact enamel (control group); II—artificial white spot lesion; III—artificial WSL treated with fluoride varnish; IV—artificial WSL treated with casein phosphopeptide—amorphous calcium phosphate (CPP-ACP) paste; V—resin-infiltrated artificial WSL. The surface microhardness was determined using the Oliver–Pharr method and a spherical indenter (Shimadzu Indenter, Kyoto, Japan). One-way analysis of variance (ANOVA) followed by a Post Hoc test (Bonferroni) was used with a level of significance set at p < 0.05. Results: Resin-infiltrated white spot lesions showed comparable microhardness mean value as the control group: 68.23 (±21.45) and 63.57 (±18.89), respectively (p > 0.05). Also, resin infiltration increased enamel microhardness compared to WSL values, with a statistically significant difference (p < 0.05). Fluoride varnish and CPP-ACP treatment resulted in equivalent values (50.84 ± 14.35 and 50.99 ± 15.31, respectively). Conclusions: Different WSL treatments (fluoride varnish, CPP-ACP and resin infiltration) produced comparable enamel microhardness values. Among the tested agents, resin infiltration resulted in higher microhardness values, while fluoride varnish and CPP-ACP demonstrated equivalent outcomes. Full article
(This article belongs to the Section Dental Materials)
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15 pages, 917 KB  
Article
Effect of Remineralization Products on the Microtensile Strength of Universal Dentin Bonding Systems
by Andra Claudia Tărăboanță-Gamen, Cristian Marius Toma, Vasilica Toma, Ionuț Tărăboanță, Simona Stoleriu, Veronica Serban Pintiliciuc and Sorin Andrian
Dent. J. 2025, 13(11), 493; https://doi.org/10.3390/dj13110493 - 24 Oct 2025
Cited by 3 | Viewed by 1037
Abstract
Background/Objectives: Adhesion to caries-affected dentin remains challenging due to its altered structure and composition. Remineralizing agents have been proposed to strengthen this substrate and improve bonding. This study evaluated the effect of three remineralization treatments, CPP-ACP, self-assembling peptide P11-4, and silver diamine [...] Read more.
Background/Objectives: Adhesion to caries-affected dentin remains challenging due to its altered structure and composition. Remineralizing agents have been proposed to strengthen this substrate and improve bonding. This study evaluated the effect of three remineralization treatments, CPP-ACP, self-assembling peptide P11-4, and silver diamine fluoride (SDF), on the microtensile bond strength (μTBS) of universal adhesive systems applied to caries-affected dentin, using both etch-and-rinse and self-etch strategies. Methods: Seventy human molars were sectioned and artificially demineralized to simulate caries-affected dentin. Samples were divided into ten groups: four untreated and six treated with CPP-ACP (MI Paste™), P11-4 (Curodont™ Protect), or SDF (Riva Star™). Universal adhesives were applied via etch-and-rinse or self-etch mode, followed by composite restoration. Microtensile bond strength was measured using a universal testing machine, and results were statistically analyzed with ANOVA and t-tests (p < 0.05). Results: Untreated caries-affected dentin showed significantly lower μTBS than sound dentin (C3: 18.3 ± 5.4 MPa vs. C1: 41.3 ± 2.7 MPa). Remineralization agents improved μTBS considerably. CPP-ACP achieved the highest recovery (S1: 31.8 ± 2.6 MPa; S2: 29.2 ± 4.6 MPa), nearing sound dentin levels. P11-4 yielded moderate gains (S3: 24.4 ± 6.5 MPa; S4: 24.1 ± 4.7 MPa), while SDF provided the lowest, yet significant, improvements (S5: 23.7 ± 7.5 MPa; S6: 21.3 ± 5.3 MPa). Etch-and-rinse generally produced higher μTBS than self-etch, but differences were not statistically significant (p > 0.05). Conclusions: Pre-treatment of caries-affected dentin with CPP-ACP, P11-4, or SDF enhances universal adhesive bond strength, with CPP-ACP showing the most pronounced effect. Remineralization protocols represent a valuable adjunct in restorative procedures involving compromised dentin. Full article
(This article belongs to the Section Dental Materials)
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15 pages, 3309 KB  
Article
Time-Effect Comparative Evaluation of Three Remineralizing Agents on Artificial Enamel Lesions: A SEM-EDX In Vitro Study
by Giulia Orilisi, Riccardo Monterubbianesi, Flavia Vitiello, Vincenzo Tosco, Maria Laura Gatto, Paolo Mengucci and Giovanna Orsini
J. Clin. Med. 2025, 14(20), 7389; https://doi.org/10.3390/jcm14207389 - 19 Oct 2025
Cited by 4 | Viewed by 1917
Abstract
Objective: This in vitro study quantitatively compared the time-dependent remineralization potential of three professional agents on artificially induced enamel lesions using Scanning Electron Microscopy (SEM) and energy-dispersive X-ray analysis (EDX). Methods: Sixty extracted sound molars were randomly assigned to three groups (number = [...] Read more.
Objective: This in vitro study quantitatively compared the time-dependent remineralization potential of three professional agents on artificially induced enamel lesions using Scanning Electron Microscopy (SEM) and energy-dispersive X-ray analysis (EDX). Methods: Sixty extracted sound molars were randomly assigned to three groups (number = 20): G_CPP-ACP, treated with casein phosphopeptide–amorphous calcium phosphate; G_Zn-HA, treated with zinc-hydroxyapatite; and G_F-ACP, treated with fluoridated amorphous calcium phosphate. The crown of each tooth was divided into three areas: one represented the control (CTRL, sound enamel), one underwent demineralization (DEMIN, demineralized enamel), and the third one was at first demineralized and then treated with a remineralizing agent, allowing intra-sample comparison. Artificial lesions were produced by immersion in 0.1 M lactic acid (72 h). Groups were subdivided according to remineralization time (7, 14, 21, and 28 days). Samples underwent daily treatment under a pH-cycling regimen. Surface morphology and Ca/P ratios were evaluated by SEM-EDX, and data were statistically analyzed (p < 0.05). Results: All agents promoted a progressive increase in Ca/P ratio over time, confirming a time-dependent remineralization effect. At day 7, G_Zn-HA showed higher Ca/P values, but from day 14 onward, G_F-ACP produced significantly greater mineral gain than the other groups (p < 0.05). By day 21, G_F-ACP reached Ca/P values approaching CTRL, while G_CPP-ACP and G_Zn-HA remained at lower levels, reaching a plateau respectively at 21 and 14 days. SEM observations supported these findings: G_CPP-ACP and G_Zn-HA showed partial surface recovery, whereas G_F-ACP exhibited a compact, homogeneous enamel-like structure at 28 days. Conclusions: All tested agents demonstrated time-dependent remineralization, enhanced with prolonged exposure, suggesting that the time of application represents a key factor for clinical success. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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24 pages, 1249 KB  
Systematic Review
Evaluation of Factors Affecting Fluoride Release from Fluoride Varnishes: A Systematic Review
by Maciej Dobrzyński, Agnieszka Kotela, Sylwia Klimas, Zuzanna Majchrzak, Julia Kensy, Marzena Laszczyńska, Mateusz Michalak, Zbigniew Rybak, Magdalena Fast and Jacek Matys
Materials 2025, 18(19), 4603; https://doi.org/10.3390/ma18194603 - 4 Oct 2025
Cited by 4 | Viewed by 3165
Abstract
Introduction: Fluoride varnishes are widely used in caries prevention, but the rate and duration of fluoride ion release differ depending on material composition and environmental factors. Objectives: This systematic review synthesized evidence from in vitro studies on human teeth to identify key factors [...] Read more.
Introduction: Fluoride varnishes are widely used in caries prevention, but the rate and duration of fluoride ion release differ depending on material composition and environmental factors. Objectives: This systematic review synthesized evidence from in vitro studies on human teeth to identify key factors influencing fluoride release. Methods: A systematic literature search was conducted in July 2025 in PubMed, Scopus, Web of Science, Embase, and the Cochrane Library using the terms “fluoride release” AND “varnish” in titles and abstracts. Study selection followed PRISMA 2020 guidelines, predefined eligibility criteria, and was structured according to the PICO framework. Of 484 retrieved records, 15 studies met the inclusion criteria and were analyzed qualitatively. Results: The primary outcome was the magnitude and duration of fluoride release from varnishes. Most studies reported peak release within the first 24 h, followed by a marked decline, although some formulations (e.g., Clinpro XT and Duraphat) maintained more stable long-term release. Substantial methodological heterogeneity was observed across studies, including differences in sample type, storage medium, pH, temperature, and measurement protocols, which influenced fluoride release dynamics. Reported secondary outcomes included enamel remineralization, changes in surface properties, and antibacterial activity, with bioactive additives such as CPP–ACP and TCP enhancing preventive effects. Acidic conditions consistently increased fluoride release. Conclusions: The magnitude and persistence of fluoride release from varnishes depend on both intrinsic material properties and external environmental conditions. Bioactive additives may prolong fluoride availability and provide additional preventive benefits. Full article
(This article belongs to the Special Issue Advanced Dental Materials: From Design to Application, Third Edition)
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13 pages, 516 KB  
Systematic Review
The Role of Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) in White Spot Lesion Remineralization—A Systematic Review
by Valentina Baccolini, Lígia Pereira da Silva, Liliana Teixeira, Raquel Teixeira de Sousa and Patrícia Manarte-Monteiro
J. Funct. Biomater. 2025, 16(8), 272; https://doi.org/10.3390/jfb16080272 - 25 Jul 2025
Cited by 12 | Viewed by 10989
Abstract
Amorphous calcium phosphate (ACP) is a well-established bioceramic material known to promote the remineralization of dental hard tissues. White spot lesions (WSLs) represent the initial stage of enamel demineralization and are frequently observed in patients with fixed orthodontic appliances or inadequate oral hygiene. [...] Read more.
Amorphous calcium phosphate (ACP) is a well-established bioceramic material known to promote the remineralization of dental hard tissues. White spot lesions (WSLs) represent the initial stage of enamel demineralization and are frequently observed in patients with fixed orthodontic appliances or inadequate oral hygiene. Although recommendations for remineralizing agents include both the prevention of lesion progression and the stimulation of tissue remineralization, the clinical efficacy of ACP-based materials remains under debate. This systematic review, registered in the PROSPERO database (CRD42024540595), aims to evaluate the clinical efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)-based products in the remineralization of WSLs and to compare these outcomes with those achieved using non-bioceramic approaches. Inclusion criteria comprised randomized clinical trials, prospective cohort studies, and pilot studies conducted on human subjects with WSLs affecting permanent teeth. Studies involving artificial WSLs or non-cariogenic enamel lesions were excluded. The quality of the included studies was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool. Fourteen articles met the inclusion criteria and were analyzed. The main findings indicate that CPP-ACP is clinically effective in promoting the remineralization of WSLs, although the results were inconsistent across studies. Comparisons with placebo and resin infiltration treatments revealed greater efficacy for CPP-ACP. The combination of CPP-ACP with fluoride appeared to further enhance the remineralizing effect on WSLs. Additional standardized clinical studies with longer follow-up periods are warranted to confirm these outcomes. Full article
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18 pages, 468 KB  
Review
Can New Remineralizing Agents Serve as Fluoride Alternatives in Caries Prevention? A Scoping Review
by Jekaterina Gudkina, Bennett T. Amaechi, Stephen H. Abrams and Anda Brinkmane
Oral 2025, 5(3), 47; https://doi.org/10.3390/oral5030047 - 2 Jul 2025
Cited by 2 | Viewed by 12427
Abstract
Background: Due to limitations of fluoride (F) treatment as a main caries preventive measure, it is important to consider the use of other dental caries preventive measures to reduce caries prevalence, especially in its early stages. Recently, new remineralizing agents appeared on the [...] Read more.
Background: Due to limitations of fluoride (F) treatment as a main caries preventive measure, it is important to consider the use of other dental caries preventive measures to reduce caries prevalence, especially in its early stages. Recently, new remineralizing agents appeared on the market, with their commercial availability in a variety of oral care products. Objectives: The purposes include providing a scoping review that represents caries remineralizing efficacies of only commercially available products and their existing adverse effects (if it is presented) and ensuring that only evidence-based approved products are included. Methods: The following databases were used in searching scientific literature on 28 October 2024: PubMed, PubMed Advanced Search, MeSH database, and PubMed Clinical Queries. The study selection criteria were as follows: for laboratory, in vitro, and/or in situ—remineralization of enamel-scanning electron microscopy, spectroscopy, microhardness test, light microscopy, profilometry, transverse microhardness microradiography, integrated mineral loss, light microscopy, photothermal radiometry; if it was a randomized controlled trial—CONSORT protocol, ICDAS system (to detect dental caries), diagnostic additional devices; antibacterial ability-colony forming units, DNA-based sequencing, scanning electron microscopy, crystal violet staining, and confocal laser scanning microscopy. Results: This review includes 98 papers: 14 of them describing the current status of caries patterns in the world, 60 studies (45 laboratory studies and 15 RCTs), and 24 systematic reviews were analyzed in order to detect whether new remineralizing agents can replace fluoride in further caries prevention. Conclusions: All reviewed new remineralization agents could be used without additives to treat early caries lesions, but the combination with F promotes better remineralization. Only HAP demonstrated its potential to serve as an alternative to fluoride in oral care products. However, further clinical studies are needed to prove its role in the remineralizing process of initial caries lesions. One also needs to ensure that both the clinical trials and in vitro lab studies use the best gold standards to validate any changes in the tooth structure, both remineralization and demineralization. Full article
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21 pages, 10272 KB  
Article
Fluoride Casein Phosphopeptide and Tri-Calcium Phosphate Treatments for Enamel Remineralization: Effects on Surface Properties and Biofilm Resistance
by Cecilia Carlota Barrera-Ortega, Sandra E. Rodil, Phaedra Silva-Bermudez, Arturo Delgado-Cardona, Argelia Almaguer-Flores and Gina Prado-Prone
Dent. J. 2025, 13(6), 246; https://doi.org/10.3390/dj13060246 - 30 May 2025
Cited by 6 | Viewed by 5215
Abstract
Objectives: This study aimed to compare in vitro the protective effect of two enamel remineralizing agents, a varnish containing β-tricalcium phosphate with sodium fluoride (β-TCP-F) and a paste containing casein phosphopeptide-amorphous calcium phosphate with sodium fluoride (CPP-ACP-F), on artificially demineralized human enamel. Methods: [...] Read more.
Objectives: This study aimed to compare in vitro the protective effect of two enamel remineralizing agents, a varnish containing β-tricalcium phosphate with sodium fluoride (β-TCP-F) and a paste containing casein phosphopeptide-amorphous calcium phosphate with sodium fluoride (CPP-ACP-F), on artificially demineralized human enamel. Methods: A total of 120 human third molar enamel specimens were randomly assigned to four groups (n = 30 each): Group I (healthy enamel, control), Group II (initially demineralized, lesioned enamel), Group III (demineralized enamel and treated with β-TCP-F), and Group IV (demineralized enamel and treated with CPP-ACP-F). Groups II–IV underwent, for 15 days, a daily pH cycling regimen consisting of 21 h of demineralization under pH 4.4, followed by 3 h of remineralization under pH 7. Groups III and IV were treated with either β-TCP-F or CPP-ACP-F, prior to each 24 h demineralization–remineralization cycle. Fluoride ion release was measured after each pH cycle. Surface hardness, roughness, wettability, and Streptococcus mutans biofilm formation were assessed on days 5, 10, and 15 after a daily pH cycle. Results: CPP-ACP-F treatment showed a larger improvement in surface hardness (515.2 ± 10.7) compared to β-TCP-F (473.6 ± 12.8). Surface roughness decreased for both treatments compared to initially lesioned enamel; however, the decrease in roughness in the β-TCP-F group only reached a value of 1.193 μm after 15 days of treatment, a significantly larger value in comparison to healthy enamel. On the other hand, the decrease in roughness in the CPP-ACP-F treatment group reached a value of 0.76 μm, similar to that of healthy enamel. Contact angle measurements indicated that wettability increased in both treatment groups (β-TCP-F: 71.01°, CPP-ACP-F: 65.24°) compared to initially lesioned samples in Group II, reaching WCA values similar to or smaller than those of healthy enamel surfaces. Conclusions: Both treatments, β-TCP-F and CPP-ACP-F, demonstrated protective effects against enamel demineralization, with CPP-ACP-F showing superior enhancement of surface hardness and smoother enamel texture under in vitro pH cycling conditions. β-TCP-F varnish and CPP-ACP-F paste treatments counteracted surface modifications produced on human healthy enamel by in vitro demineralization. Full article
(This article belongs to the Special Issue Dental Materials Design and Application)
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