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The Journal of EVIDENCE-BASED DENTAL PRACTICE REVIEW ARTICLE EFFECT OF RESIN INFILTRATION TECHNIQUE ON IMPROVING SURFACE HARDNESS OF ENAMEL LESIONS: A SYSTEMATIC REVIEW ANDMETA-ANALYSIS MEHRNAZ ZAKIZADE, DDSa, AMIN DAVOUDI, DDSb, ALI AKHAVAN, DDS, MSc, AND FARINAZ SHIRBAN, DDS, MSd aDepartment of Orthodontics, Dental School, Isfahan University of Medical Sciences, Isfahan, Iran bDental Implants Research Center, Department of Prosthodontics, Dental School, Isfahan University of Medical Sciences, Isfahan, Iran cDental Materials Research Center, Department of Endodontics, Dental School, Isfahan University of Medical Sciences, Isfahan, Iran dDental Research Center, Department of Orthodontics, Dental School, Isfahan University of Medical Sciences, Isfahan, Iran CORRESPONDING AUTHOR: Amin Davoudi, School of Dentistry, Isfahan University of Medical Sciences, Hezarjarib St, Isfahan, Iran. E-mail: Amindvi@yahoo.com KEYWORDS Deminarilzation, Microhardness, Resin infiltration, Surface hardness, White spot lesion Conflict of Interest: The authors have no actual or potential conflicts of interest. Received 24 November 2018; revised 31 July 2019; accepted 5 November 2019 J Evid Base Dent Pract 2020: [101405] 1532-3382/$36.00 ª 2020 Elsevier Inc. All rights reserved. doi: https://doi.org/10.1016/ j.jebdp.2020.101405 ABSTRACT: Objective White spot lesion (WSL) is recognized as the first clinical sign of enamel caries; it is a very critical phase because it can be prevented from progression to frank caries by changing the surrounding destructive environment. The present study was undertaken to systematically review the effect of resin infiltration (RI) technique on surface hardness (SH) of WSL. Methods Five electronic databases were searched with proper key words. Related titles and abstracts, up to October 2018, were screened, selected, and subjected to quality assessments. After collecting data, meta-analyses were carried out to compare the effect of RI with untreated WSL and sound enamel by using the STATA software. Results A total of 4567 articles were included in the study after initial search. Finally, 10 studies were reliable enough in methodology to be included in the study. Met- adata analyses, carried out on 7 studies that compared SH of RI group with un- treated samples, showed a significant increase in SH with 3.66 mean difference (95% confidence interval 5 2.56‒4.77, Q value 5 36.07, I2 5 83.4%). However, meta-analysis on 4 studies that compared SH of RI with sound enamel showed a significant decrease in SH with 22.35 overall mean difference (95% confidence interval 5 23.91–0.98, P 5 .00, Q value 5 31.75, I2 5 90.6%). Conclusion The RI technique can enhance SH of WSL; however, regaining the SH of RI- treated WSLs similar to sound enamel is doubtful. Application of RI is more effective than other methods, including application of fluoride, enamel pro- varnish, adhesive, and colloidal silica infiltration for enhancing SH of WSLs. INTRODUCTION Dental caries is a multifactorial disease that is mostly characterized by structural mineral loss of the enamel beneath an apparently intact surface June 2020 1 http://crossmark.crossref.org/dialog/?doi=10.1016/j.jebdp.2020.101405&domain=pdf https://doi.org/10.1016/j.jebdp.2020.101405 https://doi.org/10.1016/j.jebdp.2020.101405 Table 1. Applied Medical Subject Headings and non- Medical Subject Headings keywords. Population “Teeth” OR “caries” OR “dental caries” OR “initial caries” OR “Smooth surface lesion” OR “subsurface demineralization” OR “white spot lesion” OR “incipient caries” OR “non cavitated lesion” OR “incipient lesion” OR “Developmental Defect” OR “Molar Incisor Hypomineralization” OR “Tooth demineralization” OR “enamel caries” OR “enamel Hypoplasia” OR “dental enamel Hypoplasia” OR “enamel Hypocalcification” OR “initial caries lesions” OR “artificial enamel lesions” OR “natural enamel lesion” OR “caries like lesion” Intervention “Resin Infiltration” OR “Icon Resin Infiltration” OR “Commercially Available Infiltrant” OR “Microinvasive Dentistry” OR “Minimally Invasive Dentistry” OR “Minimum Intervention Dentistry” OR “Resin Infiltrant” OR “Experimental Resin Infiltrant” OR “Synthetic Resin Infiltrant” OR “Low Viscosity Resin Infiltrant” OR “Infiltration” OR “Infiltrant” OR “Infiltrating” Comparison “Placebo” OR “Placebos” OR “Microinvasive Treatment” OR “Therapeutics” OR “Fluoride” OR “Fluorides” OR “Sodium Fluoride” OR “Tin Fluoride” OR “Stannous Fluoride” OR “Fluoride Varnish” OR “Fluoride Gel” OR “Fluoride Application” OR “Fluoride Therapy” OR “Fluoride Application” OR “Fissure Sealant” OR “Pit And Fissure Sealant” OR “Sealing” OR “Surface Sealing” OR “Control Group” OR “Control Groups” OR “Cpp-Acp” OR “Casein Phosphopeptide-Amorphous Calcium Phosphate Nanocomplex” OR “Mi Paste” OR “Mi Paste Plus” OR “Colloidal Silica” OR “Finishing” OR “Polishing” OR “Dental Polishing” OR “Microabrasion” OR “Enamel Microabrasion” OR “Preventive Dentistry” OR “Operating Dentistry” OR “Sound Enamel” OR “Adhesive System” OR “Nano Hydroxy Apatite Paste” Outcome “Surface Texture” OR “Surface Microhardness” OR “Enamel Surface Properties” OR “Mechanical Properties” OR “Surface Characteristics” OR “Surface Properties” OR “Hardness” OR “Microhardness” OR “Surface Hardness” OR “Vickers Test” OR “Knoop Test” The Journal of EVIDENCE-BASED DENTAL PRACTICE 2 layer.1 As a result, “white spot lesion” (WSL), which is the first clinical sign of enamel caries, is produced and recognized by its whitish appearance because of increased porosity of the enamel surface.2 This phase of the lesion is very important because it can be reversed from the cavitation process if favorable environmental conditions can be provided.3 Different treatment strategies have been introduced by researchers to prevent progression of WSL and reestablish the enamel structure. Chemical treatment protocols are mainly based on remineralization of the enamel with the aid of fluoride-derived agents or topical treatment with amelogenin-derived peptide and calcium-derived prod- ucts.4,5 Administration of resin-based materials is a me- chanical treatment strategy for WSL, which has attracted the attention of clinicians recently. These resin-based materials mostly consist of triethylene glycol dimethacry- late (TEGDMA), which has a viable ability to penetrate into the porous structure of the lesion body, occluding the interrod spaces of WSLs, limiting ionic diffusion, and finally slowing the progression of the WSL.6 Hence, the sealed lesion becomes resistant to cariogenic acid byproducts because the resin monomers serve as a barrier and slow down or even arrest the destruction process of enamel.7 Preservation of sound hard substance, permanent occlusion maintenance, and esthetic outcomes are some other advantages of using this treatment method.8 Evaluating surface hardness (SH) is 1 of the possible ways to assess improvements in WSL after using resin infiltration (RI) technique.9 Although this measurement technique cannot directly present the mineral content changes of the WSL during treatment with RI, it can reflect the positive improvements in the treatment of WSL.9 Neres et al.10 investigated SH of WSL after using the RI technique and reported that this technique significantly increased the SH of RI-treated WSLs, compared to untreated ones. This finding was consistent with other studies that highlighted the para- mount effects of RI in increasing the SH of WSLs.11,12 Nevertheless, there is no consensus about the effectiveness of this technique for increasing resistance to other oral environmental challenges.9,10,12 Moreover, surveying different effective aspects of using RI techniques for treatment of WSL seems to be in headlines lately.13,14 Therefore, the present study systematically reviewed the role of RI technique on SH of demineralized enamel or WSL by answering the following question: “What are the effects of using RI treatment on final SH of WSL compared to other treatmentmethods or untreated WSLs?” The null Volume 20, Number 2 hypothesis of this study was that using RI technique does not improve the SH of demineralized enamel or WSL. Figure 1. Flowchart of searching strategy. The Journal of EVIDENCE-BASED DENTAL PRACTICE MATERIALS AND METHODS This systematic review was conducted according to the guidelines of Preferred Reporting Items for Systematic Re- views and Meta-Analysis (PRISMA) statement.15 Search Strategy At the beginning, a PICO question was defined to screen the articles on enamel lesions or WSL (P, population) which are treated with RI technique (I, intervention), compared with other treatment methods, or untreated WSL, or sound enamel (C, comparison), in the improvement of SH (O, outcome). The key words were selected based on Medical Subject Headings and non-Medical Subject Headings terms in simple or multiple conjunctions (Table 1). Embase, Scopus, Cochrane, PubMed, and ProQuest databases were searched thoroughly, up to October 2018, with no applied filtering or limitations except language filter (Only studies in the English language were the targets.) (Figure 1). Moreover, a hand search was carried out to obtain the articles that were probably missed. Selection of Studies Two authors (M.Z. and A.D.) independently searched the databases using the mentioned search strategy and studied the titles and abstracts of the relevant studies based on defined inclusion and exclusion criteria (Table 2). The full texts of each study that met the inclusion criteria were obtained. June 2020 3 Table 2. Inclusion and exclusion criteria. Inclusion criteria Exclusion criteria � English-language studies that investigated the effect of resin infiltration technique on enamel lesions in improvement of surface hardness � Research on at least 5 specimens in each group � Case reports � Editorial letters � Pilot studies � Historical reviews � Studies in languages other than English � Studies qualified as “high risk” based on adopted critical appraisal tool The Journal of EVIDENCE-BASED DENTAL PRACTICE 4 Assessment of the Risk of Bias Each selected study was evaluated for inner-methodological risk of bias according to an appraisal tool adopted from a similar study,16 which analyzes the terms of selection, performance, blinding of hardness evaluator, and other sources of bias. The scoring of this scale is as follows: high risk of bias (2), moderate risk of bias (1), low risk of bias (0). Then, the final risk of bias of each article was calculated and classified into 3 categories: low risk (scored ˂4), moderate risk (scored 4‒7), and high risk (scored $8). If there was any disagreement between the 2 authors, a third author (F.S.) took part, reviewed the disagreement, and reported the final opinion. After the critical appraisal of the selected studies and excluding the high-risk studies (Figure 2), the remaining studies were selected for final data collection. The following data were collected for each study: authors, publication year, sample size, the method of demineralization, grouping, the examined tests, mean SH, and final outcomes. After gathering information, the data were sent to an in- dependent statistician and epidemiologist to prepare a metadata analysis. Two separate meta-analyses were carried out to compare SH of the resin-infiltrated WSL with that of untreated WSL (Figure 3) and sound enamel (Figure 4) by using the STATA software (StataCorp, College Station, TX). For statistical analysis, a random-effects model with a con- fidence interval of 95% and meta-analytical method of in- verse variance was used. This variability model is directly related to the sample size; the larger the sample size, the Volume 20, Number 2 lower the variability and, therefore, the greater the weight of a given study in the meta-analysis measure estimate. RESULTS AND DISCUSSION A flow diagram of the search strategy is presented in Figure 1. The initial search resulted in a total of 4567 articles (167 on Embase, 20 on Cochrane, 1492 on Scopus, 51 on MEDLINE [PubMed], and 2837 on ProQuest). After excluding 2509 duplicate studies, 95 articles were included in the abstract analysis phase. Then, 20 articles remained for full-text screening, of which 8 studies were excluded as they did not conform to PICO13,17–23 (Table 3). No systematic review or a meta-analysis of this subject area was found. After assessing the bias risk of the remaining articles, 2 ar- ticles were excluded as they were considered high risk (Table 4).31,32 Finally, 10 articles9–12,25–30 were selected for quantitative analysis of data and preparation of an evidence table (Figure 1). The correlation coefficients between the two authors in the full-text levels were 0.91. All the articles were in moderate risk state (Figure 2). The descriptive results and recorded parameters of each study are presented in Table 5. All the reviewed articles were in vitro, describing a total of 473 specimens. In 5 articles, artificial WSLs were made on human enamel specimens and in 5 articles on bovine enamel specimens. All the articles used Vickers SH test except 2,9,10 which used Knoop test for measuring the SH. The applied load for measurement was different between the studies. Three studies used a 25-g load9,10,27; 2 studies used a 50-g load12,30; 2 studies applied a 100-g load25,26; and the 3 remaining ones used 200-g11,28 and 300-g29 loads. All the studies used a 10-s dwell time for applying force except for 4 studies,11,25,28,29 which applied a 15-s dwell time for measuring the SH. In most studies, the initial WSL was produced by a demineralizing solution, but 1 study28 used demineralize- remineralize cycling to create WSLs; another 19 used 3 different methods (demineralize/remineralize cycling, methylcellulose gel, and methyl-ethyl diphosphonate so- lution). There were some varieties in the RI technique between the studies. All the studies used HCl as a pre- treatment technique except for 127 that used phosphoric acid gel, which has a weaker acidic pH. One of the studies11 tried an additional pretreatment procedure before applying RI by staining the specimens with 0.1% ethanolic solution of tetramethyl rhodamine isothiocyanate dye (for 12 hours) after etching with HCl and drying with ethanol. The forest plots of meta-analysis results of 7 studies11,12, 25–28,30 (comparing RI samples with untreated samples) Figure 2. Bias risk of included articles. The Journal of EVIDENCE-BASED DENTAL PRACTICE and 4 studies11,25–27 (comparing RI samples with sound enamel) are shown in Figures 3 and 4, respectively. To decrease the heterogeneity of the collected data as much as possible, only studies that used Vickers hardness test were included in metadata analysis. Also, 1 study that reported only median and interquartile ranges was Figure 3. Forest plot of studies that compared resin-infiltrat SMD, standardized mean difference. excluded as the estimation of mean and standard deviation did not seem to be precise enough.29 The accompanying Forest plots and the weight of each study are also shown. There is no statistically significant difference in the outcome of each study (ie, no effect) when its horizontal line, representing the 95% confidence ed samples with untreated ones. CI, confidence interval; June 2020 5 Figure 4. Forest plot of studies that compared resin-infiltrated samples with sound enamel. CI, confidence interval; SMD, standardized mean difference Table 3. Excluded studies at full-text level with reason. Study Reason for exclusion Crombie et al. 201418 Using hypomineralized enamel Kumar et al. 201624 Using hypomineralized enamel Elhiny et al. 201623 Treating resin-infiltrated samples with low-pH solution before measuring surface hardness Paris et al. 201320 Measuring transverse microhardness Tostes et al. 201422 Using nanoindenter Andrade Neto et al. 201619 Measuring transverse microhardness Taher et al. 201221 Not on enamel lesion Peng et al. 201617 Not on enamel lesion The Journal of EVIDENCE-BASEDDENTAL PRACTICE Volume 20, Number 26 interval, touches the zero (vertical) line. There is also no significant difference when a horizontal vertex of the diamond, which represents the 95% confidence interval of the overall mean of difference, touches the zero line. In spite of significant heterogeneity of the included studies (Q value 5 36.07, I2 5 83.4%), the overall mean difference was 3.66 (95% confidence intervals: 2.56 and 4.77), showing a significant increase in SH of RI treatment compared with untreated samples (P 5 .00) (Figure 3). Also, the overall mean difference of the RI treatment compared to sound enamel was 22.35 (95% confidence interval: 23.91 and 20.98), showing a significant decrease in SH (P 5 .00, Q value 5 31.75, I2 5 90.6%) (Figure 4). Five studies measured SH of RI-treated lesions after exposing them to some environmental challenges to see whether they became resistant or not.9,10,12,29,27 Results on the resistance of RI-treated WSLs to acid challenges are controversial.10,12 Five studies compared the RI technique with other methods of treating lesions.11,12,28–30 Three studies used a light- curing, fluoride-releasing, single-component total-etch adhesive (ExciTE F; Ivoclar Vivadent) for their interven- tion.28–30 Moreover, some studies used enamel pro- Table 4. Critical appraisal of the included studies. Author Teeth free of caries or restoration Teeth randomization Sample size calculation Materials used according to manufacturers’ instructions Intervention performed by a single operator Blinding of the hardness evaluators Risk Neres et al.10 0 1 1 0 1 2 Moderate Gurdogan et al.25 0 0 1 0 1 2 Moderate Prajapati et al.26 0 2 1 0 1 2 Moderate Zhoa and Ren27 1 0 1 1 1 2 Moderate Arslan et al.28 0 1 1 0 1 2 Moderate Mandava et al.11 0 0 1 2 1 2 Moderate Torres et al.12 0 2 1 0 1 2 Moderate Yazkan and Ermis29 1 0 1 0 1 2 Moderate Freitas et al.9 1 0 1 0 1 2 Moderate El- Zankalouny et al.30 0 0 1 0 1 2 Moderate Aziznezhad et al.31 0 1 2 1 2 2 High Pancu et al.32 0 2 2 0 2 2 High The Journal of EVIDENCE-BASED DENTAL PRACTICE varnish,28 colloidal silica infiltration,11 fluoride,12 and casein phosphopeptide-amorphous calcium phosphate (CPP- ACP).30 One study used microabrasion, with or without polishing, for treating the lesions.29 This systematic review investigated the effects of the RI technique on promotion of the SH of WSL. According to the reviewed studies, the presumed null hypothesis was rejec- ted as most of the studies claimed that RI was able to in- crease SH of WSL. They observed that the low viscosity of resin enables it to penetrate deeper into the lesion body, fill the spaces between the remaining crystals of the porous lesion, and create a diffusion barrier not only at the surface but also within the enamel lesion.33 Thus, the weakened demineralized enamel can be strengthened by replacing the lost minerals with resin polymers.20,34 It seems that the infiltrated resin was able to encapsulate the hydroxyapatite crystals of the lesion and form a relatively uniform resin-hydroxyapatite complex with high SH.27 In spite of the agreement on the enhancement of SH by RI, there is still 1 question: Can RI treatment reestablish the sound enamel SH? TEGDMA is the main organic compo- nent of RI materials, particularly ICON-Infiltrant.35,36 June 2020 7 Table 5. Detailed information of included studies. Study Sample Demineralization method Intervention and sample size Examined test Test detail Mean hardness (kg/ mm2) ConclusionTest Control Neres et al. 201710, Brazil 50 permanent bovine incisors Demineralization solution (pH 5, 1 d) RI (Icon) (10) G0: sound enamel (10) G1: untreated lesion (10) G2: RI 1 brushing (10) G3: RI 1 pH cycling (10) G4: RI 1 artificial aging (10) Knoop (Buehler 5114, USA) 5 indentation 25-g load 10-s dwell time RI 5 228.3 6 15.4 G0 5 351.2 6 22.6 G1 5 117.8 6 13.4 G2 5 227.2 6 10.9 G3 5 30.9 6 3.8 G4 5 237.3 6 19.0 RI , G0 (P , .05) RI . G1 (P , .05) RI 5 G2 5 G4 RI . G3 Gurdogan et al. 201725, Turkey 60 bovine incisors Demineralizing solution (pH: 4, 2h) RI (Icon) (20) G0: sound enamel (20) G1: untreated lesion (20) Vickers (Buehler 5114, USA) 4 indentation 100-g load 15 s RI 5 347.55 6 24.42 G0 5 359.48 6 10.65 G1 5 257.63 6 11.86 RI 5 G0 (P 5 .073) RI . G1 (P 5 .001) Prajapati et al. 201726, India 30 human premolars Demineralizing solution (pH: 4.3, 21 d) RI (Icon) (10) G0: sound enamel (10) G1: untreated enamel (10) Vickers (CLEMEX CMT HD) 5 indentation 100-g load 10 s RI 5 12.12 6 4.6 G0 5 234.2 6 48.38 G1 5 5.9 6 1.53 RI , G0 RI . G1 (P 5 .001) Zhoa and Ren 201627, USA 20 human third molar Demineralization solution (pH: 4.5, 2 d) RI (Icon) (20) G0: sound enamel (20) G1: untreated lesion (20) G2: RI 1 thermocycling (10) G3: RI 1 water storage (10) Vickers (HMV-2T, Japan) 3 indentation 25-g load 10-s dwell time RI 5 212.0 6 45.6 G0 5 315.2 6 31.9 G1 5 89.3 6 24.1 G2 5 202.9 6 55.2 G3 5 209.6 6 35.6 RI , G0 (P , .01) RI . G1 (P , .01) RI 5 G2 Arslan et al. 201528, Turkey 60 human anterior central incisors Demineralize/ remineralize solution RI (Icon) (15) G1: untreated lesion (15) G2: enamel pro varnish (15) G3: Excite F (15) Vickers (HMV-700, Japan) 3 indentation 2-n load 15-s dwell time RI 5 318.240 6 43.91 G1 5 30.646 6 25.826 G2 5 109.577 6 47.40 G3 5 36.607 6 23.654 RI . G1 (P , .05) RI . G2 . G3 5 G1 (P , .05) Mandava et al. 201711, India 40 human maxillary central incisors Demineralizing solution (pH 4.4, 96h) RI (Icon) (20) G0: sound enamel (20) G1: untreated (20) G2: colloidal silica infiltration (20) Vickers (400 series, wilson wolpert, Germany) 3 indentation 300-g load 15-s dwell time RI 5 101.77 G1 5 75.63 G2 5 86.76 RI . G1 RI . G2 (P , .001) Torres et al. 201212, Brazil 30 bovine incisors (60 specimens) Demineralizing solution (pH: 5.0, 16h) RI (Icon) (15) G1: untreated (15) G2: daily use of fluoride solution (15) G3: weekly use of fluoride gel (15) G4: immersion in artificial saliva (15) G5: RI 1 acid challenge (15) Vickers (FM-700, future-tech, Japan) 3 indentation 50-g load 10 s RI 5 160.83 6 91.11 G1 5 19.67 6 8.43 G2 5 107.75 6 67.38 G3 5 83.25 6 51.17 G4 5 45.18 6 29.17 RI . G1 (P , .001) RI . G2 . G3 . G4 (P , .001) RI . G5 (P , .001) The Jo urnalo f E V ID E N C E -B A SE D D EN TA L PRA C TIC E Vo lum e 20, N um b er 2 8 Yazkan and Ermis, 201829, Turkey 80 bovine incisors Demineralization solution (pH 5, 10 d) RI (Icon) (16) G0: sound enamel (16) G1: untreated enamel (16) G2: RI 1 further demineralization (16) G3: RI with an adhesive resin (Excite F) (16) G4: microabrasion without polish (16) G5: micro abrasion 1 polish (16) G6: immersion in distilled water (16) Vickers (Duroline M, Turkey) 3 indentation 200-g load 15 s RI 5 261.9 G0 5 330.8 G1 5 131.7 G2 5 212.6 G3 5 211.6 G4 5 304.5 G5 5 305.6 G6 5 131.7 RI 5 G0 (P . .05) RI . G1 (P , .05) RI5 G45 G5 . G3 . G6 RI 5 G2 (P . .05) Freitas et al. 20189, Brazil 39 bovine incisors A: demineralization/ remineralization cycling (13) B: 8% methylcellulose gel (13) C: methyl ethyl diphosphonate solution (13) A, B, and C: RI (Icon) (39) G1 (on A, B, and C): untreated enamel (39) G2 (on A, B, and C): RI 1 further demineralization (39) Knoop (Wilson Tukon 1102, USA) 5 indentation 25-g load 10 s DSHa: A: RI 5 242.81 6 20.67% G1 5 291.76 6 9.17% G2 5 258.54 6 8.15% B: RI 5 262.80 6 20.52% G1 5 275.20 6 9.04% G2 5 292.25 6 15.16% C: RI 5 248.46 6 21.28% G1 5 292.50 6 3.60% G2 5 266.81 6 8.17% A&C: RI . G1 A: RI 5 G2 B&C: RI . G2 El-Zankalouny et al. 201630, Egypt 28 human premolars Demineralizing solution (pH 4.4, 4 d) RI (Icon) (7) G1: untreated enamel (7) G2: CPP-ACP (7) G3: Excite F adhesive (7) Vickers (NM) 3 indentation 50-g load 10 s RI 5 188.61 6 10.25 G1 5 149.03 6 8.65 G2 5 176.03 6 6.44 G3 5 167.26 6 8.31 RI . G1 (P 5 .009) RI . G2 . G3 (P 5 .009) CPP-ACP, casein phosphopeptide-amorphouscalcium phosphate; G, group; NM, not mentioned; RI, resin infiltration. aDSH 5 surface hardness loss (%) compared to the sound surface hardness mean. The Jo urnalo fE V ID EN C E -B A SED D EN TA L PRA C TIC E Jun e 2 0 2 0 9 The Journal of EVIDENCE-BASED DENTAL PRACTICE 10 Although this monomer has a high degree of conversion, the formation of the polymeric chain does not always happen.37 Therefore, disability of forming a strong intermolecular secondary bond, plus material shrinkage during polymerization, might result in the detection of some regions of noninfiltrated demineralized enamel that has lower SH than sound enamel. Zhoa and Ren27 and Prajapati et al.26 confirmed these findings too. Nevertheless, Gurdogan et al.25 reported that although SH of RI-treated lesions was lower than that of sound enamel, the difference was not statistically significant. They claimed that RI can enhance the hardness of the lesion to reach the sound enamel properties as well.25 The results of our meta- analysis confirmed that the RI technique cannot return the SH of WSL to that of sound enamel; however, more studies are needed to analyze the precise decision. Before applying resin infiltrates, researchers had to create WSL artificially. The artificial WSL might be induced by different methods. Freitas et al.9 used methylcellulose gel, but because of its high viscosity, the diffusion rate of the acid was compromised, resulting in a lower degree of demineralization with fewer pores.38 As a result, resin monomers might not make a good interaction with superficial crystals.26 That might be the reason why the RI technique was not able to improve the SH of enamel in these specimens as much as other demineralizing agents.26 Another method of demineralization is to use a demineralizing-remineralizing cycle, which is a dynamic process, similar to what actually happens in the oral cavity by allowing an intensive ion exchange and consequently with higher demineralization rate than other methods. However, demineralizing agents were used in most of the articles for induction of artificial lesions because of their easy availability. Compared with RI treatment, some other methods have been tried to treat the WSL. Colloidal silica infiltration, enamel pro-varnish, fluoride application, and CPP-ACP are some of those methods investigated by Mandava et al.,11 Arslan et al.,28 Torres et al.,12 and Zankalouny et al.,30 respectively. Nevertheless, most of them found the RI technique more effective than these methods in terms of enhancing lesion’s SH. The colloidal silica infiltration with 8.3-nm particles might have been lodged in the enamel voids, sealing the porous structures, but they may not be capable enough to penetrate into the voids with a smaller diameter than their actual particle size.11 Therefore, some demineralized enamel regions might remain unsealed with low SH values, consequently.11 However, resin monomers with low viscosity are much more flowable and can penetrate deeper into enamel microporosities by their capillary action.11 Enamel pro-varnish (with 5% sodium fluoride) also contained ACP, which enhanced fluoride Volume 20, Number 2 release from the varnish.39 As discussed before, resin infiltrates from a diffusion barrier not only on the surface but also within the lesion body; however, fluoride varnish creates a shallower coating layer and forms a diffusion barrier just on the surface with a probable lower SH.33 CPP-ACP is a nano-complex remineralizing agent that serves as a calcium-phosphate reservoir, prevents deminer- alization, and promotes remineralization of enamel subsur- face lesions.40 It needs saliva for deposition of calcium ions in the WSL.41 That might be the reason for increased SH values of the treated specimens over a period of 2 weeks,30 which is different from the RI technique as it improves the SH values immediately after application. Three studies28-30 examined ExciTE F adhesive to compare with the RI technique, and all reported that the RI technique was more effective. This might be attributed to nonhomogeneous and partially polymerized layer of ExciTE F adhesive because of its solvent (water).42 “Icon” resin, which is more formal for the RI technique in research studies, has a lower viscosity than ExciTE F.42 Lower viscosity, high surface tension, and low contact angle on the enamel result in high penetration coefficient for Icon,43 enabling it to fill the spaces between the remaining crystals of the porous lesion appropriately to enhance SH (Figure 5).45,46 Microabrasion, with or without polishing, is another microinvasive treatment for noncavitated lesions.47,48 During microabrasion technique, mostly the superior layers of enamel are affected by repeated application of an acid and abrasive compounds.48,49 Yazkan and Ermis29 claimed that this technique can lead to improved SH similar to the RI technique. Acid components used in this technique might change the enamel prismatic structure and induce a compacting effect on the enamel, which can enhance the SH.44 In addition to improving the SH of WSL, it is important that treated lesion become resistant to future exposure to intraoral challenges. Resin-infiltrated lesions are resistant to mechanical challenges and artificial aging, which is attrib- uted to the barrier action of resin and occluded pores of WSL.10 The results of the RI technique to pH cycles and acidic challenges were different among studies.10,12 Neres et al.10 showed that the RI technique did not make WSLs resistant to acid challenges. However, Torres et al.12 reported the opposite results. Although they observed reduced SH of RI-treated WSL after acid exposure, the SH was still significantly higher than that of the control samples. This could be due to partial dissolution of the remaining minerals in the lesion’s body that were not completely embedded by the resin matrix, or it can be a result of resin shrinkage during light-curing and further leakage and consequently reduction in acid resistance.50 Another reason Figure 5. Penetration of RI on WSL displayed by polarization microscopy and Scanning Electron Microscope (SEM). The asterisks show a residual surface layer. Resin (R), carious lesion (C), residual surface layer (*), enamel (E). RI, resin infiltration; WSL, white spot lesion. (Adopted with copyright permission No.4537811273507 from Schneider et al.’s study44). The Journal of EVIDENCE-BASED DENTAL PRACTICE might be the composition of resin infiltrates in which TEGDMA is a highly hydrophilic monomer with less resistance to degeneration in the oral environment.47 In summary, more documents are needed on the effects of microabrasion, resistance of RI-treated WSL to aging, me- chanical challenges, and acid challenges. Researchers are encouraged to conduct more clinical studies on RI and focus on the issues mentioned previously in their future studies. One of the limitations of this study was that all the articles discussed in this review were in vitro studies, so they were not able to investigate the role of saliva, curing shrinkage, and expansion of resin by intraoral thermal cycling. More- over, the artificial enamel lesions are mostly limited by the superior layers of enamel; however, in clinical situations, the lesions might be more extensive.51 As oral health care is a component of the general health that can affect the patient’s quality of life, “dental patient-reported outcome” has been focused lately. Dental patient-reported outcome suggests what really matters to patients.52 Therefore, knowing the patient-perceived impact of the RI technique in the treatment of WSLs seems to be important. In addition, RI treatment of WSLs seems to have intangible benefits, which mostly needs to be evaluated objectively by a clini- cian, and it can indirectly affect the tangible general health benefits.53 According to Hujoel’s category, the RI technique is a treatment with “clinical significance of level 3,” which has a paramount effect on the therapeutichealth care because it gives researchers a clue to conduct influential randomized clinical trials.53 CONCLUSION In general, and within the limitations of this systematic re- view, it can be concluded that the RI technique has a sig- nificant advantage for enhancing the SH of WSL; however, reestablishing the SH of resin-infiltrated WSLs similar to sound enamel is doubtful. RI was more effective for enhancing the SH than other methods (such as fluoride application, enamel pro-varnish, ExciTE F adhesive, and colloidal silica infiltration); however, more studies are needed for conclusive statements. REFERENCES 1. Hicks J, Garcia-Godoy F, Flaitz C. Biological factors in dental caries enamel structure and the caries process in the dynamic process of demineralization and remineralization (part 2). J Clin Pediatr Dent 2004;28(2):119-24. 2. Kidd EA, Fejerskov O. What constitutes dental caries? Histo- pathology of carious enamel and dentin related to the action of cariogenic biofilms. J Dent Res 2004;83(Spec No C):C35-8. 3. Featherstone JD. The caries balance: the basis for caries man- agement by risk assessment. Oral Health Prev Dent 2004;2(suppl 1):259-64. June 2020 11 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref1 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref1 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref1 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref1 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref2 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref2 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref2 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref3 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref3 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref3 The Journal of EVIDENCE-BASED DENTAL PRACTICE 12 4. Tickle M, O’Neill C, Donaldson M, et al. A randomized controlled trial of caries prevention in dental practice. J Dent Res 2017;96(7):741-6. 5. Lv X, Yang Y, Han S, et al. Potential of an amelogenin based peptide in promoting reminerlization of initial enamel caries. Arch Oral Biol 2015;60(10):1482-7. 6. Kielbassa AM, Ulrich I, Werth VD, Schuller C, Frank W, Schmidl R. External and internal resin infiltration of natural proximal subsurface caries lesions: a valuable enhancement of the internal tunnel restoration. Quintessence Int 2017;48(5): 357-68. 7. Paris S, Meyer-Lueckel H. Inhibition of caries progression by resin infiltration in situ. Caries Res 2010;44(1):47-54. 8. Kantovitz KR, Pascon FM, Nobre-dos-Santos M, Puppin- Rontani RM. Review of the effects of infiltrants and sealers on non-cavitated enamel lesions. Oral Health Prev Dent 2010;8(3): 295-305. 9. Freitas M, Nunes LV, Comar LP, et al. In vitro effect of a resin infiltrant on different artificial caries-like enamel lesions. Arch Oral Biol 2018;95:118-24. 10. Neres EY, Moda MD, Chiba EK, Briso A, Pessan JP, Fagundes TC. Microhardness and roughness of infiltrated white spot lesions submitted to different challenges. Oper Dent 2017;42(4):428-35. 11. Mandava J, Reddy YS, Kantheti S, et al. Microhardness and penetration of artificial white spot lesions treated with resin or colloidal silica infiltration. J Clin Diagn Res 2017;11(4): ZC142-Z146. 12. Torres CR, Rosa PC, Ferreira NS, Borges AB. Effect of caries infiltration technique and fluoride therapy on microhardness of enamel carious lesions. Oper Dent 2012;37(4):363-369. 13. Faghihian R, Shirani M, Tarrahi MJ, Zakizade M. Efficacy of the resin infiltration technique in preventing initial caries progres- sion: a systematic review and meta-analysis. Pediatr Dent 2019;41(2):88-94. 14. Borges AB, Caneppele TM, Masterson D, Maia LC. Is resin infiltration an effective esthetic treatment for enamel develop- ment defects and white spot lesions? A systematic review. J Dent 2017;56:11-18. 15. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535. 16. Astudillo-Rubio D, Delgado-Gaete A, Bellot-Arcís C, Montiel- Company JM, Pascual-Moscardó A, Almerich-Silla JM. Me- chanical properties of provisional dental materials: a systematic review and meta-analysis. PLoS One 2018;13(2):e0193162. 17. Peng Y, Qian Z, Ting Z, Jie F, Xiaomei X, Li M. The effect of resin infiltration vs. fluoride varnish in enhancing enamel surface conditions after interproximal reduction. Dent Mater J 2016;35(5):756-761. Volume 20, Number 2 18. Crombie F, Manton D, Palamara J, Reynolds E. Resin infiltration of developmentally hypomineralised enamel. Int J Paediatr Dent 2014;24(1):51-55. 19. Andrade Neto DM, Carvalho EV, Rodrigues EA, et al. Novel hydroxyapatite nanorods improve anti-caries efficacy of enamel infiltrants. Dent Mater 2016;32(6):784-793. 20. Paris S, Schwendicke F, Seddig S, Muller WD, Dorfer C, Meyer- Lueckel H. Micro-hardness and mineral loss of enamel lesions after infiltration with various resins: influence of infiltrant composition and application frequency in vitro. J Dent 2013;41(6):543-548. 21. Taher NM, Alkhamis HA, Dowaidi SM. The influence of resin infiltration system on enamel microhardness and surface roughness: an in vitro study. Saudi Dent J 2012;24(2):79-84. 22. Tostes MA, Santos E Jr, Camargo SA Jr. Effect of resin infiltra- tion on the nanomechanical properties of demineralized bovine enamel. Indian J Dent 2014;5(3):116-122. 23. Elhiny O, Elattar H, Salem G. The influence of resin infiltration system on sound enamel microhardness and shear-bond strength of orthodontic bands: an in-vitro study. Der Pharma Chemica 2016;8:100-106. 24. Kumar H, Palamara JEA, Burrow MF, Manton DJ. An investi- gation into the effect of a resin infiltrant on the micromechanical properties of hypomineralised enamel. Int J Paediatr Dent 2017;27:399-411. 25. Gurdogan EB, Ozdemir-Ozenen D, Sandalli N. Evaluation of surface roughness characteristics using atomic force micro- scopy and inspection of microhardness following resin infiltra- tion with Icon((R)). J Esthet Restor Dent 2017;29(3):201-208. 26. Prajapati D, Nayak R, Pai D, Upadhya N, K Bhaskar V, Kamath P. Effect of resin infiltration on artificial caries: an in vitro evalua- tion of resin penetration and microhardness. Int J Clin Pediatr Dent 2017;10(3):250-256. 27. Zhao X, Ren YF. Surface properties and color stability of resin- infiltrated enamel lesions. Oper Dent 2016;41(6):617-626. 28. Arslan S, Zorba YO, Atalay MA, et al. Effect of resin infiltration on enamel surface properties and Streptococcus mutans adhesion to artificial enamel lesions. Dent Mater J 2015;34(1): 25-30. 29. Yazkan B, Ermis RB. Effect of resin infiltration and microabrasion on the microhardness, surface roughness and morphology of incipient carious lesions. Acta Odontol Scand 2018;76(7): 473-481. 30. El-Zankalouny SM, El Fattah WMA, El-Shabrawy SM. Penetra- tion depth and enamel microhardness of resin infiltrant and traditional techniques for treatment of artificial enamel lesions. Alexandria Dent J 2016;41(1):20-25. 31. Aziznezhad M, Alaghemand H, Shahande Z, et al. Comparison of the effect of resin infiltrant, fluoride varnish, and nano-hy- droxy apatite paste on surface hardness and streptococcus http://refhub.elsevier.com/S1532-3382(20)30009-9/sref4 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref4 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref4 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref5 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref5 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref5 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref6 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref6 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref6 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref6 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref6 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref7 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref7 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref8 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref8http://refhub.elsevier.com/S1532-3382(20)30009-9/sref8 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref8 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref9 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref9 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref9 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref10 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref10 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref10 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref10 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref11 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref11 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref11 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref11 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref12 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref12 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref12 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref13 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref13 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref13 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref13 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref14 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref14 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref14 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref14 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref15 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref15 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref15 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref16 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref16 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref16 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref16 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref17 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref17 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref17 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref17 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref18 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref18 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref18 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref19 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref19 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref19 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref20 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref20 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref20 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref20 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref20 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref21 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref21 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref21 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref22 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref22 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref22 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref23 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref23 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref23 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref23 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref53 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref53 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref53 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref53 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref27 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref27 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref27 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref27 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref28 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref28 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref28 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref28 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref31 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref31 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref26 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref26 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref26 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref26 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref30 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref30 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref30 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref30 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref29 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref29 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref29 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref29 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref24 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref24 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref24 The Journal of EVIDENCE-BASED DENTAL PRACTICE mutans adhesion to artificial enamel lesions. Electron Physician 2017;9(3):3934-42. 32. Pancu G, Andrian S, Iovan G, et al. Study regarding the assessment of enamel microhardness in incipient carious le- sions treated by icon method. Rom J Oral Rehabil 2011;3: 94-100. 33. Meyer-Lueckel H, Paris S. Improved resin infiltration of natural caries lesions. J Dent Res 2008;87(12):1112-6. 34. Askar H, Lausch J, Dorfer CE, Meyer-Lueckel H, Paris S. Pene- tration of micro-filled infiltrant resins into artificial caries lesions. J Dent 2015;43(7):832-8. 35. Catelan A, Briso AL, Sundfeld RH, Dos Santos PH. Effect of artificial aging on the roughness and microhardness of sealed composites. J Esthet Restor Dent 2010;22(5):324-30. 36. Paris S, Lausch J, Selje T, Dorfer CE, Meyer-Lueckel H. Com- parison of sealant and infiltrant penetration into pit and fissure caries lesions in vitro. J Dent 2014;42(4):432-8. 37. Gajewski VE, Pfeifer CS, Froes-Salgado NR, Boaro LC, Braga RR. Monomers used in resin composites: degree of conversion, mechanical properties and water sorption/solubil- ity. Braz Dent J 2012;23(5):508-14. 38. Damato FA, Strang R, Stephen KW. Comparison of solution- and gel-prepared enamel lesions–and in vitro pH-cycling study. J Dent Res 1988;67(8):1122-5. 39. Jablonowski BL, Bartoloni JA, Hensley DM, Vandewalle KS. Fluoride release from newly marketed fluoride varnishes. Quintessence Int 2012;43(3):221-8. 40. Shen P, Cai F, Nowicki A, Vincent J, Reynolds EC. Reminerali- zation of enamel subsurface lesions by sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phos- phate. J Dent Res 2001;80(12):2066-70. 41. Bailey DL, Adams GG, Tsao CE, et al. Regression of post-or- thodontic lesions by a remineralizing cream. J Dent Res 2009;88(12):1148-53. 42. Meyer-Lueckel H, Paris S, Mueller J, Colfen H, Kielbassa AM. Influence of the application time on the penetration of different dental adhesives and a fissure sealant into artificial subsurface lesions in bovine enamel. Dent Mater 2006;22(1):22-8. 43. Gugnani N, Pandit IK, Gupta M, Josan R. Caries infiltration of noncavitated white spot lesions: a novel approach for imme- diate esthetic improvement. Contemp Clin Dent 2012;3(suppl 2):S199-202. 44. Schneider H, Park KJ, Rueger C, Ziebolz D, Krause F, Haak R. Imaging resin infiltration into non-cavitated carious lesions by optical coherence tomography. J Dent 2017;60:94-8. 45. Meyer-Lueckel H, Paris S. Progression of artificial enamel caries lesions after infiltration with experimental light curing resins. Caries Res 2008;42(2):117-24. 46. Ardu S, Castioni NV, Benbachir N, Krejci I. Minimally invasive treatment of white spot enamel lesions. Quintessence Int 2007;38(8):633-6. 47. Murphy TC, Willmot DR, Rodd HD. Management of post- orthodontic demineralized white lesions with microabrasion: a quantitative assessment. Am J Orthod Dentofacial Orthop 2007;131(1):27-33. 48. Lynch CD, McConnell RJ. The use of microabrasion to remove discolored enamel: a clinical report. J Prosthet Dent 2003;90(5): 417-9. 49. Fragoso LS, Lima DA, de Alexandre RS, Bertoldo CE, Aguiar FH, Lovadino JR. Evaluation of physical properties of enamel after microabrasion, polishing, and storagein artificial saliva. Biomed Mater 2011;6(3):035001. 50. Paris S, Meyer-Lueckel H, Colfen H, Kielbassa AM. Resin infil- tration of artificial enamel caries lesions with experimental light curing resins. Dent Mater J 2007;26(4):582-8. 51. Park J, Eslick J, Ye Q, Misra A, Spencer P. The influence of chemical structure on the properties in methacrylate-based dentin adhesives. Dent Mater 2011;27(11):1086-93. 52. John MT. Health outcomes reported by dental patients. J Evid Based Dent Pract 2018;18(4):332-5. 53. Hujoel PP. Levels of clinical significance. J Evid Base Dent Pract 2004;4:32-6. June 2020 13 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref24 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref24 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref25 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref25 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref25 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref25 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref32 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref32 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref33 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref33 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref33 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref34 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref34 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref34 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref35 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref35 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref35 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref36 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref36 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref36 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref36 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref37 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref37 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref37 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref38 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref38 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref38 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref39 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref39 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref39 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref39 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref40 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref40 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref40 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref41 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref41 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref41 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref41 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref42 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref42 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref42 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref42 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref48 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref48 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref48 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref43 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref43 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref43 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref44 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref44 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref44 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref45 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref45 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref45 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref45 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref46 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref46 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref46 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref47 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref47 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref47 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref47 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref49 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref49 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref49 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref50 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref50 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref50 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref51 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref51 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref52 http://refhub.elsevier.com/S1532-3382(20)30009-9/sref52 Effect of Resin Infiltration Technique on Improving Surface Hardness of Enamel Lesions: A Systematic Review and Meta-analysis Introduction Materials and Methods Search Strategy Selection of Studies Assessment of the Risk of Bias Results and Discussion Conclusion References