In-vitro and in-vivo comparative studies of treatment effects on enamel demineralization during orthodontic therapy: implications for clinical early-intervention strategy.

OBJECTIVES: This study aimed to investigate if CPP-ACP / infiltrating resin was superior in treating enamel demineralization during orthodontic therapy compared with fluoride varnish, in order to provide early-intervention implications for dental professionals. MATERIALS AND METHODS: In the in-vitro study, premolars were grouped into four: remineralization with fluoride varnish / CPP-ACP, sealing with infiltrating resin, and negative control. Experimental demineralization of enamel surfaces was analyzed using techniques of QLF, SEM, EDS and micro-hardness testing. An in-vivo intervention study was conducted on patients randomly assigned into three groups. At the baseline and every-3-month follow-up, QLF parameters were compared temporally and parallelly to yield potential implications for promotion in clinical practice. RESULTS: The in-vitro study performed on 48 experimental tooth surfaces demonstrated that sealing with infiltrating resin reduced enamel surface porosity and increased surface micro-hardness significantly. In the in-vivo intervention study on 163 tooth surfaces, it was suggested that for those who meet the criteria of -10 < ΔF < -6 and - 1000 < ΔQ < -20 at the baseline, all these treatment methods could achieve acceptable outcomes; with the rising of absolute values of ΔF and ΔQ, sealing with infiltrating resin showed more evident advantages. CONCLUSION: For enamel demineralization during orthodontic therapy, all the treatment methods involved in this study showed acceptable effectiveness but had respective characteristics in treatment effects. QLF parameters could be used as indicators for clinical early-intervention strategy with regards to this clinical issue. CLINICAL RELEVANCE: With QLF parameters, clinical early-intervention strategy for enamel demineralization during orthodontic therapy could be optimized.

Effects of graphene oxide and graphene quantum dots on enhancing CPP-ACP anti-caries ability of enamel lesion in a biofilm-challenged environment.

OBJECTIVE: To investigate the anticaries effects of graphene oxide (GO) and graphene quantum dots (GQDs) combined with casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on enamel in a biofilm-challenged environment. MATERIAL AND METHODS: GO and GQDs were synthesised using citric acid. The antibiofilm and biofilm inhibition effects for Streptococcus mutans were evaluated by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and colony-forming units (CFU). Remineralisation ability was determined by assessing mineral loss, calcium-to-phosphorus ratio, and surface morphology. To create a biofilm-challenged environment, enamel blocks were immersed in S. mutans to create the lesion and then subjected to artificial saliva/biofilm cycling for 7 days. Anticaries effects of GO, GQDs, GQDs@CPP-ACP, GO@CPP-ACP, and CPP-ACP were determined by broth pH and mineral changes after 7-day pH cycling. Biocompatibility was tested using a Cell Counting Kit-8 (CCK8) assay for human gingival fibroblasts (HGF-1). RESULTS: GQDs and GO presented significant antibiofilm and biofilm inhibition effects compared to the CPP-ACP and control groups (P < 0.05). The enamel covered by GQDs and GO showed better crystal structure formation and less mineral loss (P < 0.05) than that covered by CPP-ACP alone. After 7 days in the biofilm-challenged environment, the GO@CPP-ACP group showed less lesion depth than the CPP-ACP and control groups (P < 0.05). GO and GQDs showed good biocompatibility compared to the control group by CCK8 (P > 0.05) within 3 days. CONCLUSION: GO and GQDs could improve the anti-caries effects of CPP-ACP, and CPP-ACP agents with GO or GQDs could be a potential option for enamel lesion management. CLINICAL SIGNIFICANCE: GO and GQDs have demonstrated the potential to significantly enhance the anticaries effects of CPP-ACP. Incorporating these nanomaterials into CPP-ACP formulations could provide innovative and effective options for the management of enamel lesions, offering improved preventive and therapeutic strategies in dental care.

Assessment of the Additive Effect of Remineralizing Agents in Combination With Fluoride Releasing Adhesives in the Prevention of Enamel Decalcification in Orthodontic Patients: An In Vitro Study.

Introduction Incorporation of remineralizing agents with fluoride-releasing bracket adhesives may prevent the development of white spot lesions (WSL) or reverse the established WSL in patients undergoing fixed orthodontic treatment. We aimed to find out how effectively casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and fluoride varnish (FV) can remineralize teeth when mixed with fluoride-releasing orthodontic adhesive. Materials and methods We randomly assigned a total of 60 premolar teeth, therapeutically extracted for orthodontic purposes, into two equal groups. Group I (n = 30) utilized fluoride-releasing adhesive (FR), and Group II (n = 30) bonded with non-fluoride adhesive (NFR). Based on the applied remineralizing agent, we further divided each of the two groups into three equal subgroups of 10: Group IA (FR+FV), Group IB (FR+CPP-ACP), Group IC (control-only FR), Group IIA (NFR+FV), Group IIB (NFR+CPP-ACP), and Group IIC (control-only NFR). Following bonding procedures, all the samples underwent pH cycling for 28 days, where the enamel samples were immersed in 20 ml of demineralizing solution for three hours, followed by immersion in 30 ml of remineralizing solution for 17 hours. The samples were analyzed for shear bond strength (SBS) on a universal testing machine and hardness values (HV) by the Vickers microhardness test (VMT) using the indentation method. We also evaluated the adhesive remnant index (ARI) scores to determine the site of bracket failure. Statistical analysis The shear bond strength (SBS) and hardness value (HV) were expressed as the mean, standard deviation (SD), and median for each subgroup. We used the non-parametric Kruskal-Wallis test to analyze the SBS and HV, followed by the Dunn-Bonferroni test for intra-pair differences. The ARI score was expressed as the frequency of the percentage distribution, and the difference in the distribution of ARI scores between the groups was assessed by the Cochran chi-square test. The probability (p) value equal to or less than 0.05 was considered statistically significant. Results The results show that Group IB, bonded with a fluoride-releasing adhesive and a CPP-ACP remineralizing agent surface treatment, has the highest HV of 300.23 units. Group IIC (only NFR) has the lowest hardness of 153.3 units, which is statistically significant (p < 0.001). However, the ARI scores are not statistically significant between the groups tested. Conclusion The bond strength of the adhesive and the surface hardness of the enamel increased with the addition of fluoride varnish and CPP-ACP to both the fluoride-releasing and non-fluoride-releasing adhesives.

Remineralization efficiency of three different agents on artificially produced enamel lesions: A micro-CT study.

OBJECTIVE: This study aimed to assess the remineralization efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), silver diamine fluoride/potassium iodide (SDF/KI), and sodium fluoride with functionalized tricalcium phosphate (NaF/fTCP) on artificial early enamel lesion using laser fluorescence and micro-CT analysis. METHODOLOGY: On extracted impacted third molars, artificial enamel lesions were prepared. Twenty-eight specimens were randomly assigned to four groups (n = 7 per group): a control group (artificial saliva), CPP-ACP (GC Tooth Mousse), SDF/KI (Riva Star), and NaF/fTCP (Clinpro White varnish). Following the manufacturer's instructions, the remineralization agents were applied to demineralized surfaces. Laser fluorescence and micro-CT were used to evaluate the remineralization efficacy of the agents and analyzes were performed during four stages: before demineralization, after demineralization, 1st day of remineralization and 30th day of remineralization. Shapiro-Wilk test, repeated measures two-way ANOVA, and Spearman correlation tests were used for statistical analysis. A significant level of p < 0.05 was established. RESULTS: SDF/KI significantly reduced the lesion area and lesion volume on the demineralized enamel surface after 30 days of remineralization. In the T3 period, SDF/KI increased the mineral density statistically significantly compared to the T1 period. The laser fluorescence values for all three remineralizing agents exhibited a linear decrease. A significant correlation between the fluorescence values and the mineral density was found (p = 0.01). CONCLUSION: All three investigated agents were showed positive remineralization efficacy on artificial enamel lesion. However, SDF/KI, containing silver diamine fluoride and potassium iodide exhibited superior than other agents in promoting remineralization. CLINICAL SIGNIFICANCE: Although all three remineralization agents showed positive remineralization efficacy on artificial enamel lesions, SDF had higher remineralization performance over the other two agents. SDF has potential to prevent progression of demineralization in treating children with high caries risk in the long-term.

Comparative Evaluation of Remineralizing Potential of Topical Cream Containing Casein Phosphopeptide-Amorphous Calcium Phosphate and Casein Phosphopeptide-Amorphous Calcium Phosphate with Fluoride: An In Vitro Study.

The requirement for clinically effective treatments to remineralize early enamel caries lesions is dictated by the principles of minimally invasive dentistry. Numerous studies outlined the significance of treating early carious lesions with different remineralizing agents. This study aimed to evaluate and compare the remineralization potential of topical cream containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and CPP-ACP with fluoride in remineralizing artificial carious lesions on enamel. Forty-five freshly extracted human premolar teeth were selected as samples. These samples were divided into three groups: Group I-regular toothpaste without specific remineralizing agent; Group II-topical cream containing CPP-ACP and Group III topical cream containing CPP-ACP with fluoride. All the samples were viewed under scanning electron microscope (SEM) to assess the topographical pictures of the enamel surface and also subjected to energy dispersing X-ray analysis (EDX) for quantitative estimation of minerals, calcium (Ca), and phosphorous (P). In the result of the study, Group I does not show any increase in the Ca and P after applying toothpaste without any remineralizing agent but Group II and Group III showed a net increase in Ca and P- values after applying concerned remineralizing agents. Intergroup comparison showed Group III yielded higher net Ca and P- values than Group II. Two remineralizing agents showed remineralization potential on samples. Descriptive statistics were used to calculate the mean and standard deviation. Mann-Whitney test was used. The level of significance was set at 0.05. CPP-ACP containing fluoride showed better remineralizing potential than CPP-ACP. Hence, CPP-ACP containing fluoride can be considered the material of choice in remineralizing early enamel carious lesions.

Layer-by-layer self-assembly of PLL/CPP-ACP multilayer on SLA titanium surface: Enhancing osseointegration and antibacterial activity in vitro and in vivo.

Dental Implants are expected to possess both excellent osteointegration and antibacterial activity because poor osseointegration and infection are two major causes of titanium implant failure. In this study, we constructed layer-by-layer self-assembly films consisting of anionic casein phosphopeptides-amorphous calcium phosphate (CPP-ACP) and cationic poly (L-lysine) (PLL) on sandblasted and acid etched (SLA) titanium surfaces and evaluated their osseointegration and antibacterial performance in vitro and in vivo. The surface properties were examined, including microstructure, elemental composition, wettability, and Ca2+ ion release. The impact the surfaces had on the adhesion, proliferation and differentiation abilities of MC3T3-E1 cells were investigated, as well as the material's antibacterial performance after exposure to the oral microorganisms such as Porphyromonas gingivalis (P. g) and Actinobacillus actinomycetemcomitans (A. a). For the in vivo studies, SLA and Ti (PLL/CA-3.0)10 implants were inserted into the extraction socket immediately after extracting the rabbit mandibular anterior teeth with or without exposure to mixed bacteria solution (P. g & A. a). Three rabbits in each group were sacrificed to collect samples at 2, 4, and 6 weeks of post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the implant osseointegration. The modified titanium surfaces were successfully prepared and appeared as a compact nano-structure with high hydrophilicity. In particular, the Ti (PLL/CA-3.0)10 surface was able to continuously release Ca2+ ions. From the in vitro and in vivo studies, the modified titanium surfaces expressed enhanced osteogenic and antibacterial properties. Hence, the PLL/CPP-ACP multilayer coating on titanium surfaces was constructed via a layer-by-layer self-assembly technology, possibly improving the biofunctionalization of Ti-based dental implants.

Effect of Casein Phosphopeptide-Amorphous Calcium Phosphate, Proanthocyanidin, Carbon Dioxide Laser Remineralization on the Bond Integrity of Composite Restoration Bonded to Caries-Affected Dentin.

Objective: Assessment of different remineralizing pretreatment casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), proanthocyanidin (PA), carbon dioxide laser (CO2), eggshell solution (ES) on the shear bond strength (SBS) of resin composite bonded to remineralized carious-affected dentin (CAD). Materials and methods: Eighty human molars were collected with occlusal caries that extended about halfway into the dentin. Using a water-cooled, low-speed cutting saw, a flat, mid-coronal dentin surface was exposed. CAD was differentiated from healthy dentin. Based on the remineralizing agent used on the CAD surface, the teeth were arbitrarily allocated into five groups (n = 10). Group 1: no remineralizing agent, Group 2: CPP-ACP, Group 3: 6.5% PA solution, Group 4: CO2 laser, and Group 5: ES solution. All samples were bonded to composite and light cured and thermocycled. SBS and failure mode analysis were performed using universal testing and stereomicroscope 40 × . Using SPSS, SBS, and failure mode data were analyzed using analysis of variance and Tukey's honesty significant difference (HSD) test Results: Group 3 (6.5% PA solution; 15.59 ± 1.44 MPa) samples established the maximum bond integrity. Nevertheless, Group 1 (No remineralizing agent; 11.19 ± 1.21 MPa) exhibited the minimum outcome of bond strength. Intergroup comparison analysis showed that Group 1 (No remineralizing agent), Group 2 (CPP-ACP), and Group 4 (CO2 laser) established comparable values of bond strength (p > 0.05). Likewise, Group 3 (6.5% PA solution) and Group 5 (EA solution) also revealed equivalent bond integrity (p > 0.05). Conclusions: PA and ES are considered potential remineralizing agents used for caries-affected dentin surfaces in improving bond integrity to composite resin. However, further studies are advocated to extrapolate the findings of this study.

Remineralisation of enamel and dentine with stabilised stannous fluoride dentifrices in a randomised cross-over in situ trial.

OBJECTIVES: To compare the remineralisation efficacy and ion bioavailability of two novel SnF2-containing dentifrices in a blinded, cross-over, randomised in situ clinical study. METHODS: Six participants wore removal palatal appliances holding human enamel and dentine blocks with subsurface lesions. Appliances were worn for two treatment periods of 14 consecutive days each, with a one-week washout period in-between. Participants were randomly allocated to rinse with a 1:5 diluted coded slurry of one of two dentifrices containing either 5 % casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) +1100 ppm F as SnF2 [MIPOP], or 1100 ppm F as SnF2 [CT], for 1 min, four times a day. Saliva was collected post-treatment and analysed for tin, calcium, inorganic phosphate and fluoride ions using atomic absorption spectrophotometry and ion chromatography. Enamel and dentine lesions were analysed for percent remineralisation (%R) using transverse microradiography and percent surface microhardness recovery (%SMHR). RESULTS: MIPOP released significantly higher F (3.00 ± 0.27 mM), Ca (15.23 ± 3.23 mM) and Sn (1.18 ± 0.13 mM) into saliva whereas CT released 2.89 ± 0.32 mM F and only 0.84 ± 0.11 mM Ca and 0.28 ± 0.10 mM Sn. MIPOP produced significantly higher %R than CT: 25.6 ± 1.5 % compared to 15.2 ± 0.7 % in enamel, and 33.6 ± 3.1 % compared to 20.6 ± 1.1 % in dentine. Additionally, MIPOP produced significantly higher %SMHR (18.2 ± 7.9 %) compared to CT (4.1 ± 0.6 %). CONCLUSIONS: Both dentifrices promoted remineralisation, but the MIPOP dentifrice with added CPP-ACP and the ion-stabilising effects of CPP released higher amounts of bioavailable tin and produced significantly higher remineralisation and surface microhardness recovery. CLINICAL SIGNIFICANCE: Modern dentifrices contain SnF2 for a range of oral health benefits. Challenges associated with stability of these formulations can affect ion bioavailability, reducing efficacy. Two dentifrices with SnF2 promoted remineralisation in situ, however the dentifrice with the added saliva biomimetic CPP-ACP was superior and therefore may produce greater health benefits.

Effect of Two Remineralizing Agents on Dentin Microhardness of Non-Caries Lesions.

Statement of the Problem: The prevalence of non-carious dentin lesions is on the rise mainly due to improved life expectancy. Successful management of these lesions is often challenging, and given that dentin can be remineralized, adverse consequences due to progression of these lesions can be prevented or minimized as such. Purpose: This study aimed to assess the effect of casein phosphopeptide amorphous calcium phosphate (CPP-ACP) and Remin-Pro remineralizing agents on dentin microhardness of non-carious dentin lesions. Materials and Method: This in vitro, experimental study evaluated 36 extracted sound human premolars. The teeth were decoronated at the cementoenamel junction. Enamel was removed, and dentin was exposed at the cervical third of the buccal surface. The primary microhardness of dentin was then measured. The teeth, standardized in terms of dentin microhardness, then underwent demineralization by acid etching and were subjected to microhardness test again. They were then randomized into three groups for treatment with CPP-ACP, Remin-Pro, and artificial saliva (control), and dentin microhardness was measured for the third time after treatment. Data were analyzed using ANOVA. Results: Within group comparisons showed a significant difference in microhardness at the three time points in all three groups (p< 0.005). Between-group comparisons revealed that the microhardness of the three groups was not significantly different at baseline or after demineralization. However, the microhardness of the three groups was significantly different after the intervention (p= 0.000). Pairwise comparisons revealed significantly higher microhardness in the CPP-ACP group than the other two groups (p= 0.003). Remin-Pro and the control groups were not significantly different in this respect (p= 0.340). Conclusion: CPP-ACP can be used for remineralization of non-caries dentin lesions; however, Remin-Pro does not appear to be effective for this purpose.

Estimation of the Efficacy of Remineralizing Agents on the Microhardness of Deciduous Teeth Demineralized Using Pediatric Formulations.

AIM: This study aimed to evaluate the demineralizing effect of commonly used pediatric syrup formulations on primary teeth and the efficacy of two readily available remineralizing agents in treating this effect. MATERIALS AND METHODS: Ninety primary teeth were used for sample preparation and divided into three groups: antibiotic syrup (group A), cough syrup (group B), and control (group C) groups. These groups were further categorized into intragroups according to the treatment with remineralizing agents: groups A1, B1, and C1 received GC Tooth Mousse (casein phosphopeptide-amorphous calcium phosphate, CPP-ACP paste) and groups A2, B2, and C2 received Clinpro Tooth Crème. The samples were subjected to a series of demineralization cycles for 14 days, and remineralization cycles until 30 days were performed using two remineralizing agents, that is, GC Tooth Mousse (CPP-ACP paste) and Clinpro Tooth Crème and were evaluated using Vicker's microhardness test. RESULTS: Antibiotic syrup (group A) and cough syrup (group B) showed a significant decrease in surface microhardness compared with control (group C). All intragroups showed an increase in surface microhardness after treatment with remineralizing agents, which was significantly higher in intragroups A1, B1, and C1 treated with GC Tooth Mousse (CPP-ACP paste). CONCLUSIONS: Oral liquid medications showed definite demineralization potential. CPP-ACP paste was found to be better than Clinpro Tooth Crème for demineralized teeth. CLINICAL SIGNIFICANCE: The use of over-the-counter drugs has increased among the average Indian population, especially for the treatment of fever, cold, and cough. Unwise use of medications by the present population without proper medical guidance will lead to irreparable changes in future generations.

Comparative Evaluation on the Effect of Different Remineralizing Agents on Enamel-Bracket Shear Bond Strength: An In Vitro Study.

AIM:  This study aimed to compare the effects of applying various remineralizing agents before and after acid etching on the enamel-bracket shear bond strength (SBS) in vitro. These agents included silver diamine fluoride (SDF), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), and 5% sodium fluoride (5% NaF). MATERIALS AND METHODS: All the selected teeth were divided equally into six subgroups depending on before and after acid etching and one separate control group for the in vitro study design. Eighty-four extracted premolar teeth (12 teeth in each group x seven groups, including the control group). Before acid etching, teeth in groups A1, B1, and C1 were given SDF, CPP-ACP paste, and 5% NaF, respectively. Following acid etching, all of the teeth in Groups A2, B2, and C2 received the same preventative treatments. After that, the SBS of the bonded brackets to the enamel was evaluated. RESULTS: The CPP-ACP group, control group, and SDF group had the highest values for SBS prior to acid etching.The 5% NaF group had the weakest bonds, and the difference between the groups was statistically significant. The CPP-ACP group had the highest SBS following acid etching, followed by the 5% NaF group. The least bond strength was seen in the SDF group, and the difference between the three groups was significant. CONCLUSION: When it comes to bonding orthodontic brackets, the CPP-ACP pretreatment is superior to fluoride pretreatment in terms of effectiveness. The use of these remineralizing agents resulted in favorable values that did not have any effect on the SBS and were therefore safe to use with orthodontic brackets.

Improving Oral Health with Fluoride-Free Calcium-Phosphate-Based Biomimetic Toothpastes: An Update of the Clinical Evidence.

As the demand for clinically effective fluoride-free oral care products for consumers increases, it is important to document which types of toothpastes have been shown in clinical studies to be effective in improving oral health. In this review, we included different indications, i.e., caries prevention, improving periodontal health, reducing dentin hypersensitivity, protecting against dental erosion, and safely improving tooth whitening in defining what constitutes improvement in oral health. While there are several professional and consumer fluoride-containing formulations fortified with calcium-phosphate-based ingredients, this review focuses on fluoride-free toothpastes containing biomimetic calcium-phosphate-based molecules as the primary active ingredients. Several databases were searched, and only clinical trials in human subjects were included; in vitro and animal studies were excluded. There were 62 oral health clinical trials on biomimetic hydroxyapatite (HAP), 57 on casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), 26 on calcium sodium phosphosilicate (CSPS, or so called Bioglass), and 2 on ß-tricalcium phosphate (ß-TCP). HAP formulations were tested the most in clinical trials for benefits in preventing caries, dentin hypersensitivity, improving periodontal health, and tooth whitening. Based on the current clinical evidence to date, fluoride-free HAP toothpaste formulations are the most versatile of the calcium phosphate active ingredients in toothpastes for improving oral health.

Long term remineralizing effect of casein phosphopeptide amorphous calcium phosphate in white spot lesions: A systematic review and meta-analysis.

BACKGROUND: White spot lesions (WSLs) appear as white, opaque areas on the teeth and are caused by a demineralization of the enamel. OBJECTIVE: The purpose of this systematic review and meta-analysis was to determine whether casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has beneficial effects on WSLs and provides remineralizing benefits that are superior to those of placebo or no treatment. METHODS: Following a thorough analysis of the literature across major online sources, 103 papers - 54 of which underwent in-depth evaluation - were found. We used inclusion and exclusion criteria to choose research articles that were appropriate for our review. RESULTS: 10 papers met this review's requirements and were subsequently included. As compared to the controls, CPP-ACP demonstrated increased efficacy in treatment of WSLs in terms of remineralisation and other parameters which included microhardness tests and enamel surface roughness. The forest plots present the results of meta-analyses comparing the effect of CPP-ACP versus control/other agents on white spot lesions (WSLs). In terms of odds ratios (OR), CPP-ACP showed a small increase in the odds of WSLs compared to control/other agents. In-vitro studies showed no significant difference in relative risk (RR) between CPP-ACP and control/other agents. Randomized control trials indicated a small increase in the risk of WSLs with CPP-ACP treatment, but the overall effect was not statistically significant. CONCLUSION: There was evidence to support the use of CPP-ACP over other agents for WSL prevention or treatment, but further research is needed to confirm these findings.

Comparative evaluation of fluoride-free remineralization agents with and without Er,Cr:YSGG laser on artificial enamel remineralization.

This study aimed to evaluate the efficacy of fluoride-free remineralizing agents in initial enamel caries, with and without combined Er,Cr:YSGG laser application. The remineralization effect of various agents and their combinations on artificial initial caries was investigated using 10 experimental groups (n = 7): NC, negative control; PC, positive control; TM, calcium-phosphate compounds (CPP-ACP); TD, theobromine-containing toothpaste; RG, ROCS® remineralizing gel; L, Er,Cr:YSGG laser (2780 nm; 0.25 W; repetition rate, 20 Hz; pulse duration, 140 µs; tip diameter, 600 µm; without air/water cooling); L + fluoride toothpaste; L + TM; L + TD; and L + RG. The demineralized bovine enamel specimens were subjected to an 8-day pH cycle by daily application of the remineralizing agents and laser therapy once prior to the pH cycle and paste application. The enamel samples underwent the Vickers surface microhardness test, and one sample per group was analyzed with scanning electron microscopy. The Kruskal Wallis test was used to compare the microhardness recovery percentage (SMHR%) for each group, and multiple comparisons were made with the Dunn test. Groups L (p = 0.003), RG (p = 0.019), L + TM (p < 0.001), L + fluoride toothpaste (p = 0.001),and L + RG (p = 0.036) exhibited significant increase in SMHR%. The tested remineralizing agents exhibited no statistically significant difference in effect when used alone and in combination with Er,Cr:YSGG laser. Combined application of Er,Cr:YSGG laser and ROCS® remineralization gel effectively promoted enamel remineralization, while use of CPP-ACP and fluoride toothpaste alone was ineffective. Theobromine-containing toothpaste exhibited the least SMHR%. Long-term evaluation of these agents is recommended.

Shear bond strength of metallic brackets bonded to enamel pretreated with CPP-ACP: a systematic review and meta-analysis of in vitro studies.

BACKGROUND: Development of white spot lesions (WSLs) is common among orthodontic patients. Several measures have been introduced to prevent and remineralize the lesions. Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is used for both prevention and remineralization. The effect of its application before bonding is controversial. This systematic review was conducted to investigate the most up to date available literature regarding the effect of CPP-ACP enamel pre-treatment on shear bond strength (SBS) of metallic orthodontic brackets. METHODS: A search was conducted in electronic databases (MEDLINE (via PubMed), Scopus, Cochrane Library, Web of Science and Google scholar (grey literature)) up to March 29th, 2023. The inclusion criteria included in vitro studies comparing the SBS of metal orthodontic brackets following pre-treatment of enamel using CPP-ACP versus control. The exclusion criteria included study types other than in vitro studies, studies conducted on non-human enamel, or studies using CPP-ACP in combination with another intervention. The included studies were analysed by two reviewers, independently. The risk of bias assessment was done using a modified risk of bias tool. A Meta-analysis was performed. I2 values and Q-test were used for assessment of heterogeneity. Results were displayed in forest plots with a random-effects model. Standardized mean difference, standard error (SE) and 95% confidence intervals were calculated for all studies. RESULTS: The search resulted in 76 articles. After duplicate removal and assessment for eligibility, 15 studies were included in the review. High statistical heterogeneity was found among the included studies using I2 values and Q-Test (I2 = 95.147%; Q = 288.456; df = 14; P < 0.001). The overall effect of CPP-ACP pre-treatment on the SBS of metal orthodontic brackets was not significant (Mean difference = 1.163 MPa, SE = 0.757, 95% CI = -0.321, 2.648, p value = 0.125). The use of CPP-ACP for prevention of WSLs did not significantly affect the SBS of brackets (Standardized mean difference = 1.009, SE = 0.884, 95% CI = -0.723, 2.740, p value = 0.254). No significant change was found when CPP-ACP was used for remineralization of WSLs (Standardized mean difference = 1.501, SE = 1.087, 95% CI = -0.630, 3.632, p value = 0.167). CONCLUSIONS: Within the limitations of the study, the evidence suggests that the use of CPP-ACP for either prevention or remineralization of WSLs before bonding does not affect the SBS of metal orthodontic brackets.

Comparison of therapies of white spot lesions: a systematic review and network meta-analysis.

OBJECTIVE: White spot lesions (WSLs), the earliest evidence of enamel demineralization, are considered amenable to intervention to achieve a remineralized or arrested state of caries. The management of WSLs is quite challenging, and there is no definitive cure as yet. We performed a network meta-analysis to assess the efficacy of seven therapies for WSLs and gave a hierarchy of them. MATERIALS AND METHODS: We systematically searched the PubMed, EMBASE, Cochrane, and Web of Science databases (last search: July 2022) to identify all relevant studies. We limited our search to studies published in English. Randomized controlled designed in vitro/clinical trials related to the efficacy of the seven therapies for WSLs were included. Data extraction was performed independently by two reviewers. The risk of bias (ROB) 2.0 tool from Cochrane and a previous in vitro methodological tool will be used for the quality assessment. Variations in quantitative light-induced fluorescence (QLF), laser fluorescence (LF), and lesions area were the primary outcome measures. Standard mean difference (SMD) was used as the effect size for the Network meta-analysis (NMA). Consistency and inconsistency tests were conducted. The hierarchy of 7 treatment effects was evaluated using surface probabilities under cumulative ranking (SUCRA). Publication bias was evaluated using a bias plot. RESULTS: Forty-two articles were included in the systematic review. Thirty-one of them, with a total of 1906 participants, were included in the network meta-analysis. The studies owned a low and moderate risk of bias. This analysis does not suffer from significant inconsistency. The difference between 4 groups 'self-assembled peptide (SAP) P11-4', 'P11-4 + Fluoride Varnish (FV)', 'Resin Infiltration (RI)', 'casein phosphor peptides-amorphous calcium fluoride phosphate (CPP-ACFP)' and the 'Control' group was found to be statistically significant. Compared to the 'FV' and 'casein phosphor peptides-amorphous calcium phosphate (CPP-ACP)' groups, the 'P11-4 + FV" group and 'RI" group made a significant difference. The hierarchy was evident in the SUCRA values of 7 therapies. P11-4 + FV and RI were considered effective therapies compared to the control group or the FV group (gold standard group). CONCLUSIONS: The available evidence suggests that resin infiltration and P11-4 in combination with fluoride varnish had advantages over gold standard (FV). The effect of tricalcium phosphate-based drugs and fluoride is not very noticeable. Overall, drugs based on P11-4 and resin infiltration will be better therapies. Using more than two drugs in combination also would increase efficacy.

Assessment of the Remineralizing Potential of Biomimetic Materials on Early Artificial Caries Lesions after 28 Days: An In Vitro Study.

This study aimed to evaluate the loss of mineral content in the enamel surface in early artificial lesions and to assess the remineralizing potential of different agents by means of SEM coupled with energy-dispersive X-ray analysis (EDX). The analysis was performed on the enamel of 36 molars divided into six equal groups, in which the experimental ones (3-6) were treated using remineralizing agents for a 28-day pH cycling protocol as follows: Group 1, sound enamel; Group 2, artificially demineralized enamel; Group 3, CPP-ACP treatment; Group 4, Zn-hydroxyapatite treatment; Group 5, NaF 5% treatment; and Group 6, F-ACP treatment. Surface morphologies and alterations in Ca/P ratio were evaluated using SEM-EDX and data underwent statistical analysis (p < 0.05). Compared with the sound enamel of Group 1, the SEM images of Group 2 clearly showed loss of integrity, minerals, and interprismatic substances. Groups 3-6 showed a structural reorganization of enamel prisms, interestingly comprising almost the entire enamel surface. Group 2 revealed highly significant differences of Ca/P ratios compared with other groups, while Groups 3-6 showed no differences with Group 1. In conclusion, all tested materials demonstrated a biomimetic ability in remineralizing lesions after 28 days of treatment.

Remineralization Strategies for Teeth with Molar Incisor Hypomineralization (MIH): A Literature Review.

Molar incisor hypomineralization (MIH) is a highly prevalent dental developmental disorder with a significant health burden for patients and high treatment needs, yet no comprehensive review article on all remineralization systems as a non-invasive treatment approach for MIH has been published. Typical characteristics of MIH-affected teeth are a lower mineral density and lower hardness compared to healthy teeth leading to sensitivity and loss of function. Thus, the use of formulations with calcium phosphates to remineralize MIH-affected teeth is reasonable. This review presents an up-to-date overview of remineralization studies focusing on active ingredients investigated for remineralization of MIH, i.e., casein phosphopeptide amorphous calcium phosphate (CPP-ACP), casein phosphopeptide amorphous calcium fluoride phosphate (CPP-ACFP), hydroxyapatite, calcium glycerophosphate, self-assembling peptide, and fluoride. Overall, 19 studies (in vitro, in situ, and in vivo) were found. Furthermore, an additional search for studies focusing on using toothpaste/dentifrices for MIH management resulted in six studies, where three studies were on remineralization and three on reduction of sensitivity. Overall, the studies analyzed in this review showed that MIH-affected teeth could be remineralized using calcium phosphate-based approaches. In conclusion, calcium phosphates like CPP-ACP, calcium glycerophosphate, and hydroxyapatite can be used to remineralize MIH-affected teeth. In addition to MIH-remineralization, CPP-ACP and hydroxyapatite also offer relief from MIH-associated tooth sensitivity.

Remineralization effect of three different agents on initial caries and erosive lesions: a micro-computed tomography and scanning electron microscopy analysis.

BACKGROUND: This study aimed to investigate the remineralization efficiency of Sensodyne Promine containing Sodium flouride (NaF), GC Tooth Mousse containing CPP-ACP, and Agarta herbal toothpaste on initial caries and erosion using micro-computed tomography (CT) and scanning electron microscopy (SEM). METHODS: Forty-five third-molar teeth for micro-CT were divided into three main groups after initial scans (T1) were completed. Artificial caries lesions were created with the demineralization cycle (group 1, n = 15) and artificial erosion lesions were created with orange juice (group 2, n = 15) and Cola (group 3, n = 15), and second scans (T2) were performed. The groups were divided into three subgroups within themselves. Sensodyne Promine toothpaste (subgroup 1a, 2a, 3a), GC Tooth Mousse topical cream (subgroup 1b, 2b, 3b), and Agarta herbal toothpaste (subgroup 1c, 2c, 3c) were applied using soft-tipped brushes for 2 min, twice per day for 15 days, and then a third scan (T3) was performed. Mineral density, surface area, and lesion volume and depth were calculated using micro-CT. Changes in the surface morphology of the teeth were examined using SEM in 13 samples representing each group, subgroup, and healthy enamel. In the analysis of the data obtained from the scans performed at three different times (T1, T2, T3), one-way analysis of variance (ANOVA) with the post-hoc Tukey test, repeated measures ANOVA with the post-hoc Bonferroni test, and paired sample t-test analyses were used. RESULTS: All three agents caused a statistically significant increase in mineral density, and a decrease in surface area and lesion volume and depth (p < 0.05). There was no statistically significant difference between the groups in remineralization efficiency (p > 0.05). A statistically significant difference was found between the groups regarding the mineral density of the tissue that increased after remineralization (NaF > CPP-ACP > He; p < 0.05). CONCLUSION: The remineralization efficacy of herbal toothpaste as an alternative to NaF and CPP-ACP was found to be successful.

Comparative evaluation of prevention of demineralization of artificial enamel caries treated with two fluoride varnishes and 38% SDF in primary teeth: an in vitro study.

BACKGROUND: This study aimed to compare the effect of Clinpro™ White varnish containing 5% sodium fluoride (NaF) and functionalized tricalcium phosphate, MI varnish containing 5% NaF and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), and 38% Silver diamine fluoride (SDF) in preventing demineralization of treated white spot lesions (WSLs) in enamel of primary teeth. METHODS: Forty-eight primary molars with artificial WSLs were allocated into four groups as follows: Group 1: Clinpro white varnish, Group 2: MI varnish, Group 3: SDF, and Group 4: control (no treatment). The three surface treatments were applied for 24 h and then enamel specimens were subjected to pH cycling. Thereafter, the mineral content of specimens was evaluated by Energy Dispersive X-ray Spectrometer and the lesion depth was assessed via Polarized Light Microscope. One-way ANOVA followed by Tukey's post hoc test were used at p ≤ 0.05 to identify significant differences. RESULTS: Insignificant difference in mineral content was observed among treatment groups. Treatment groups exhibited significantly higher mineral content compared to control except for Fluoride (F). MI varnish showed the highest mean calcium (Ca) ion content (66.57 ± 0.63), and Ca/P (2.19 ± 0.11), followed by Clinpro white varnish, and SDF. MI varnish also displayed the highest phosphate (P) ion content (31.46 ± 0.56), followed by SDF (30.93 ± 1.02), and Clinpro white varnish (30.53 ± 2.19). Fluoride content was highest in SDF (0.93 ± 1.18), followed by MI (0.89 ± 0.34) and Clinpro (0.66 ± 0.68) varnishes. Significant difference in lesion depth was observed among all groups (p < 0.001). The lowest mean lesion depth (µm) was found in MI varnish (226.23 ± 44.25) which was significantly lower than Clinpro white varnish (285.43 ± 44.70), SDF (293.32 ± 46.82), and control (576.69 ± 42.66). Insignificant difference in lesion depth was found between SDF and Clinpro varnish. CONCLUSIONS: In primary teeth, WSLs treated with MI varnish displayed better resistance to demineralization compared to WSLs treated with Clinpro white varnish and SDF.