Clinical Relevance

At 24 months, the dentin pretreatment with epigallocatechin-3-gallate did not impair the clinical performance of the adhesive Single Bond Universal regardless of the bonding strategy used.

SUMMARY

Purpose: To evaluate the two-year effect of dentin pretreatment with epigallocatechin-3-gallate (EGCG) on the clinical performance of restorations of noncarious cervical lesions (NCCLs) with Single Bond Universal, applied in two different modes (self-etch and etch-and-rinse).

Methods and Materials: In this randomized clinical trial, 33 volunteers were selected, and 156 NCCLs were assigned to four groups: ER, etch-and-rinse; ER-EGCG, 0.1% EGCG dentin pretreatment + etch-and-rinse; SE, self-etch; and SE-EGCG, 0.1% EGCG dentin pretreatment + self-etch. The NCCLs were restored with a nanofilled resin composite and evaluated at baseline and at six, 12, 18, and 24 months using FDI criteria for retention, marginal staining, marginal adaptation, caries, and postoperative sensitivity. Two evaluators were blinded to the treatments performed, and impressions were taken for resin replicas to allow indirect observations. Statistical analyses were performed with Kruskal-Wallis and McNemar tests with a significance level of 5%.

Results: Six restorations (one from ER, two from SE, one from ER-EGCG, and two from SEEGCG) were lost at 24 months with no significant differences (p>0.05). The retention rates were 97.0% (ER and ER-EGCG), 94.1% (SE), and 94.2% (SE-EGCG). For marginal adaptation, a significant difference was detected between the baseline and 24 months for the SE group (p=0.0313). There were no statistical differences among all other evaluated criteria at 24 months, neither for each group at baseline nor for 24-month comparisons (p>0.05).

Conclusions: The pretreatment with EGCG provided no benefit in the clinical performance of the adhesive regardless of the bonding strategy used. In addition, it adds an additional required step to the restorative procedure.

Randomized controlled trials are considered the ideal design for comparing different procedures in health care interventions1  and the most reliable of evidence-based studies to dental practice.2  Laboratory studies are widely used and provide faster results, but they do not take into account the complex oral environment.3  The current research in adhesive dentistry is aimed at improving the quality of the resin-dentin bonds and understanding their degradation mechanisms.4  Many strategies have been proposed to provide greater longevity of the union of the restorative materials to the dental structure, but few of them were evaluated under clinical conditions.5 

Since proteolytic degradation of the hybrid layer has been described in the literature6  and associated with the host enzymes, matrix metalloproteinases (MMP), and cysteine cathepsins (CC), numerous investigations have been conducted with potential enzymatic inhibitors. Promising laboratory results have been achieved regarding the hybrid layer preservation and long-term durability.7,8  These enzymes are present in human dentin and saliva with the ability to degrade most extracellular matrix proteins, such as collagen type I, the organic component of the hybrid layer.9,10  Within the hybrid layer, denuded collagen fibrils become vulnerable to degradation by these host-derived proteases with collagenolytic activity.11  Thus, the use of bioactive substances that inhibit the enzymes may avoid the degradation of exposed collagen fibrils at the adhesive interface.4 

Chlorhexidine (CHX) is the “gold standard” antimicrobial agent for oral health and has demonstrated inhibition of MMP-2, MMP-8, MMP-9, and CC.12,13  Laboratory results have proven the benefits in the immediate and long-term bond effectiveness of CHX associated with adhesive systems. However, the use of chlorhexidine as an MMP inhibitor was tested under clinical trials (either as dentin pretreatment or incorporated in the adhesive), 1417  and the results (up to three-year follow-up) 18  showed that there was no improvement in the clinical durability of adhesive restorations. These results also highlighted the lack of correlation between the results of the laboratory tests and the clinical reality to which the adhesive restorations are exposed.3 

Other enzymatic inhibitors, mainly natural products, have aroused the interest of the scientific community. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol found in green tea with a proven ability to inhibit the expression and action of MMP-2, MMP-9, and CC.19  Through laboratory studies, the use of EGCG has been recently associated with adhesive procedures and was effective in preserving the resin-dentin bond strength for up to six months when incorporated into the dentin adhesive20  and up to six and 12 months when used as a dentin pretreatment with etch-and-rinse (ER) and self-etch (SE) adhesive systems, respectively.21,22  Unlike CHX, EGCG also has an additional cross-linking property with positive effects on the mechanical properties of collagen and its stabilization against proteolytic degradation.23  It has been shown that galloyl radical monomeric catechins, such as EGCG, are more effective than other catechins without the radical in increasing the modulus of elasticity and reducing collagen biodegradation rates.23 

In this field, EGCG seems to be a promising bioactive substance that may maintain the integrity and stability of dentin collagen by synergistic effects, with protease inhibition and cross-linking ability in dentin. To the authors’ knowledge, there are no randomized controlled trials evaluating the effect of EGCG as a dentin primer in the restorations of noncarious cervical lesions (NCCLs).

Thus, the objective of the present study was to evaluate the influence of dentin pretreatment with EGCG in restorations of noncarious cervical lesions performed with a universal adhesive system in the two adhesive strategies in vivo. The null hypotheses tested were that (1) there is no difference between the clinical performance of NCCL restorations bonded with the ER strategy associated or not with dentin pretreatment with EGCG and (2) there is no difference between the clinical performance of NCCL restorations bonded with the SE strategy associated or not with dentin pretreatment with EGCG.

Study Design

This study was a blind, randomized clinical trial with an equal allocation rate among the four adhesive procedures under evaluation, and this report follows the Consolidated Standards of Reporting Trials statement.24  In the control groups, the multimode adhesive was applied in the ER and SE strategies. In the experimental groups (ER-EGCG and SE-EGCG), a dentin pretreatment with a 0.1% w/v EGCG aqueous solution (Sigma-Aldrich, St Louis, MO, USA) was scrubbed on the teeth for 60 seconds, and then the adhesive system was used in the same ER (ER-EGCG) and SE (SE-EGCG) strategies. Table 1 summarizes the restorative materials and the application procedures used.

Patient Selection

Thirty-three volunteers (22 to 66 years old; 19 male and 14 female) were informed about the goals of the study and the risks and benefits to which they would be exposed, were authorized to participate, and signed a written consent form. Inclusion criteria consisted of being over 18 years of age, having good oral hygiene and no periodontal disease or bruxism, and having at least four NCCLs and at least 20 teeth in occlusion. Exclusion criteria consisted of a previous cervical restorative procedure or caries lesions. All types of noncarious lesions (abrasion, erosion, and abfraction) were included, and all of them were nonretentive with no more than 50% of the margin in enamel and with the cervical margin in dentin.

Sample Size Calculation and Sample Randomization

The sample size was calculated based on the 96% retention rate of Single Bond Universal (3M ESPE, St Paul, MN, USA) in an 18-year clinical follow-up and considering a two-tailed test hypothesis.25  At least 33 restorations per group were required to determine a 25% difference between groups with a significance level of 5% and a statistical power of 80%. A 20% increase in the sample size was set, considering possible loss during the study.

The assignment was done following one random list created using the website www.sealedenvelope.com, which indicated the control or experimental group for each tooth, without the patient’s awareness.

Restorative Procedures

Each patient received at least one restoration per group for a total of 156 restorations. All NCCLs were classified according to cavity dimensions in millimeters (height, width, and depth), shape of the cavity (degree of the angle labeled as <45°, 45° to 90°, 90° to 135°, or >135°), degree of sclerotic dentin,26  presence of incisal/occlusal wear facets, presence of preoperative sensitivity, and distribution among tooth types (Table 2).

Clinical photographs of the teeth prior to restoration were taken with a digital camera (Canon EOS 60D, Canon Macro EF 100-mm lens, Canon, Tokyo, Japan) in three positions: vestibular, proximal (mesial), and incisal/occlusal. Silicone rubber impressions with heavy- and light-body polyvinylsiloxane material (Adsil, Vigodent, Rio de Janeiro, Brazil) were obtained of each NCCL to make epoxy resin (MC130/FD154, Epoxyfiber, Rio de Janeiro, Brazil) replicas.27 

The same operator performed all restorations. Twenty-seven patients received four restorations, and six patients received eight restorations. No cavity preparation was carried out, enamel margins were not beveled, and no mechanical retention was placed. Local anesthesia with 1.8 mL of 2% lidocaine hydrochloride and phenylephrine 1:2500 (S.S. White 100, S.S.White, Petrópolis, Brazil), a labial retractor (Arc Flex, FGM, Joinville, Brazil), cotton rolls, and #00 retraction cord (Ultrapak, Ultradent, Indaiatuba, Brazil) were used for all cases. Prior to the restorative procedure, the NCCLs were cleaned with pumice and water (S.S.White), then rinsed and dried.

The adhesive system’s application in the control groups (ER and SE) followed the ER and SE protocols suggested by their manufacturers (Table 1). The experimental groups (ER-EGCG and SEEGCG) followed the same protocols but with a dentin pretreatment with a 0.1% EGCG aqueous solution (Sigma-Aldrich) scrubbed on the lesions for 60 seconds (Table 1). Increments of the resin composite Filtek Z350XT (3M ESPE) (up to three) were inserted and light cured individually for 20 seconds using the LED light-curing unit DB-685 (1100 mW/cm2, Dabi Atlante, Ribeirão Preto, Brazil).

The initial finishing was performed with 12- and 30-fluted tungsten carbide burs (Microdont, São Paulo, Brazil) and F and FF diamond tips (KG Sorensen, São Paulo, Brazil). Polishing was performed with Sof-Lex Pop-On abrasive discs (3M ESPE). The initial baseline evaluation was performed one week later when another impression was taken of each restoration. New resin replicas from the restoration interface were obtained for observation under a scanning electron microscope (SEM) (Quanta FEG 450, FEI, Thermo Fisher Scientific, Hillsboro, OR, USA).

Clinical Evaluation

The study was blinded for the two independent, calibrated examiners who were responsible for the clinical evaluations. FDI World Dental Federation criteria28,29  were used to evaluate retention, the presence of fractures, marginal discoloration, marginal adaptation, caries, and postoperative sensitivity at baseline and after six, 12, 18, and 24 months. These variables were classified as follows: clinically very good, clinically good (scores 1+2), clinically sufficient/satisfactory (score 3), clinically unsatisfactory (score 4), and clinically poor (score 5).29  The analysis was done independently and performed with a clinical mirror and dental explorer #5 (EXD56, Hufriedy, Rio de Janeiro, Brazil). In case of disagreement between the investigators, a consensus was reached by reexamination and discussion before the patient was dismissed.30 

The retention rates were calculated according to the following equation: cumulative failure percentage = [(PF+NF)/(PF+RR)] × 100%, where PF is the number of previous failures before the current assessment, NF is the number of new failures during the current evaluation, and RR is the number of restorations currently evaluated.25 

At all evaluation periods (baseline and six, 12, 18, and 24 months), impressions were taken from representative restorations from each group tested and each level score from marginal adaptation criteria.27  All restorations were also photographed in two positions (vestibular and mesial).

Statistical Methods

The McNemar test was used for intragroup comparisons between the baseline and the other periods. The Kruskal-Wallis test was used for intergroup comparisons between each group in each period. The comparisons were performed for all criteria evaluated with a significance level of 5%. The Cohen kappa statistic was used to measure the agreement between examiners.

Figure 1 shows the patient’s flow diagram. Thirty-eight out of 71 patients were not enrolled in the study because they did not fulfill the inclusion criteria. Thus, 33 subjects were selected, and the one hundred and fifty-six lesions were randomly assigned to one of the four experimental groups. Recall rates were 100% for baseline for six, 12, and 18 months. For 24 months, the recall rate was 96.9%, with one patient not returning due to health problems. One patient was eliminated at 12 months and another at 18 months due to orthodontic treatment.

Table 3 presents data for retention/fractures, marginal staining, marginal adaptation, caries, and postoperative sensitivity at baseline and for all evaluation periods. The pooled (1+2) scores and score 3 present the total number of restorations classified as clinically acceptable. Scores 4 and 5 show the number of restorations considered clinically unsatisfactory. Figure 2 presents representative images of clinically satisfactory restorations from each group at baseline and at 24 months.

Four restorations were lost after six months, one restoration was lost at the 12-month recall, and one restoration was lost at the 18-month recall. Thus, a total of six restorations were lost by 24 months (one for ER, two for SE, one for ER-EGCG, and one for SE-EGCG). The 24-month retention rates were 97.1% for ER, 94.4% for SE, 97.1% for ER-EGCG, and 94.6% for SE-EGCG, with no statistical difference between any pair of groups at the 24-month recall and for each group when the baseline and 24-month results were compared (p>0.05; Table 3).

Two restorations had an acceptable material chip fracture (one for ER and one for SE), but it did not affect the marginal integrity score of 3. Six restorations had bulk fractures with partial loss for a score of 4 (two each for the SE, ER-EGCG, and SE-EGCG groups) (Figure 3).

Ten restorations were considered to have discrepancies in marginal adaptation at the 24-month recall. Half of them (one for ER and four for SE) were considered minor acceptable discrepancies, but another half (two for SE, one for ER-EGCG, and two for SE-EGCG) were considered unacceptable discrepancies, with severe material fracture (Figure 4). No significant difference was detected between any pair of groups at the 24-month recall (p>0.05), but a significant difference was detected when the baseline and 24-month data were compared within the SE group (p=0.0313) (Table 3).

Marginal staining was observed in seven restorations (one for SE, four for ER-EGCG, and two for SEEGCG). Pronounced marginal staining was observed in only one restoration, which was in the SE-EGCG group. However, no significant difference was found between groups at 24 months and within each group when the baseline and 24-month findings were compared (p>0.05; Table 3).

Three restorations had postoperative sensitivity one week after the restorative procedures (two for ER and one for SE). Two of them showed very intense sensitivity (score 4), but the sensitivity remained clinically acceptable at six, 12, and 18 months, and no restoration presented postoperative sensitivity at 24 months.

Finally, caries were not observed after 24 months of clinical service, and no tooth became nonvital as a result of the cervical restoration.

EGCG is the most abundant catechin found in green tea. It has recently been introduced into the dental field because of several promising benefits, such as its antibacterial effect,31  protective effects for dental erosion,32  and effects in preserving the resin-dentin bond strength for up to six and 12 months associated with ER and SE adhesive systems, respectively, in laboratory studies.2022 

It has been suggested that EGCG could have a superior clinical application due to its positive effects on both mechanical properties and the stabilization of collagen against proteolytic degradation.23  To the authors’ knowledge, there are no clinical reports regarding the clinical performance of adhesive systems associated with EGCG. Thus, this randomized clinical trial evaluated a universal adhesive on different adhesive strategies, assessing the influence of the dentin pretreatment with EGCG prior to the adhesive application.

After 24 months, there was no difference in the retention of NCCL restorations bonded with the ER or SE strategy, associated or not with dentin pretreatment with EGCG, which leads to failing to reject the null hypothesis.

In the current study, a 0.1% w/v EGCG aqueous solution was used as the dentin primer since it was the concentration with better laboratory results in preserving the bond strength over time.21,22  The one-minute application significantly improved the bond strength in research conducted by Zheng and Chen8  on MMP inhibitors. In the present clinical study, this time of application represented a feasible step to be reproduced in clinical practice.

The clinical efficacy of the four bonding procedures was evaluated by the retention of the restorations as a primary outcome.3  Retention in NCCLs cannot be associated with any other macromechanical retention, which can directly reflect the quality of the adhesive bonding.2  In addition, the hypermineralized dentin in NCCLs makes the bonding to this substrate very unpredictable and challenging for adhesive systems.33 

The high retention rates for all tested groups after 24 months showed that the bond effectiveness of the universal adhesive did not depend on the bonding strategy, in accordance with previous randomized clinical trials.25,3437  This retention rate result may be explained by the Single Bond Universal (SU) (3M ESPE) chemical bond mechanism. SU contains 10-methacryloxydecyl dihydrogen phosphate (10-MDP), an acidic phosphate monomer capable of bonding to hydroxyapatite, producing adhesive interfaces with different chemical and morphological characteristics. It also contains a polyalkenoic acid copolymer.25  These two processes involve micromechanical and chemical bonding to the enamel and dentin, which may have had a direct impact on the retention rate and clinical behavior of SU in the current study after 24 months.

The retention results also showed that the EGCG priming solution did not impair the bond effectiveness and can be associated with both adhesive strategies as reported only by laboratory studies.21,22  Unlike chlorhexidine, which showed a negative association with a self-etching adhesive,38  this result highlighted the versatile clinical application of EGCG as a dentin primer in NCCLs.

The scoring system used for the evaluation of the NCCL restorations was the FDI criteria.29  Four specific secondary outcomes were selected from the total of 16 original parameters. The inclusion of “marginal staining” and “marginal adaptation” was an important measure since they are still shortcomings mainly of cervical restorations and it has been indicated that they may be predictors of future failures.39  Also, a simplified clinical evaluation was chosen pooling scores 1 and 2 (equivalent to score A from the US Public Health Service criteria);30  thus, the FDI criteria were expressed with only four scores: two for acceptable (1+2 and 3) and two for nonacceptable (4 and 5) for reparable and replacement, respectively.1,29 

For marginal adaptation, a significant difference was detected when baseline and 24-month data were compared within the SE group (p=0.0313). SU is considered an ultramild SE adhesive (pH~3.0), and, although there is no consensus that pre-etching enamel improves the bond strength of universal adhesives,40,41  this result may be related to the limited micromechanical retention of the enamel surface conditioned by the SE mode. Surprisingly, the association of EGCG with the SE strategy did not jeopardize the marginal adaptation, and future evaluations could confirm a possible beneficial effect of EGCG priming on enamel.

After 24 months, five restorations were rated as score 4 (two for SE, one for ER-EGCG, and two for SE-EGCG) with unacceptable discrepancies and severe material fractures. A prophylactic repair was indicated to recover the restoration integrity, avoiding premature replacement of the restoration. 29  These restorations can be viewed as “relative failures,” and this result may be associated with heavy occlusal or parafunctional forces since all teeth presented signs of occlusal wear (data not shown). A retrospective clinical study27  showed that class V restorations of teeth with occlusal wear facets had a 6.65-fold increased risk of failure than those of teeth without wear facets. Clinical covariables shown in Table 2 could determine the bonding effectiveness, such as shape and size of the lesion, degree of sclerosis, presence of wear facets, patient age, and tooth type.

The restorations that were rated unsatisfactory were additionally investigated using digital photographs and epoxy resin replicas under SEM evaluation. 27  The replicas enabled indirect observation and were useful in analyzing changes in discrepancies and/or material fracture in restorations at different periods. This procedure was helpful in determining the need for timely repair or replacement.

Pronounced marginal staining was observed in only one restoration, which was in the SE-EGCG group, and it was associated with a color change along the whole of the restoration margin due to smoking habits and not to the marginal discrepancy.

A meta-analysis and trial sequential analysis42  evaluated randomized clinical trials comparing degradation inhibitory cavity pretreatment (CHX and quaternary ammonium) prior to the adhesive placement of the resin-based restorations. The authors concluded that there is insufficient evidence to recommend or refute degradation inhibitory cavity pretreatment prior to adhesively placing resin-based restorations. These findings corroborate the current results regarding EGCG since its effects (protease inhibition and cross-linking ability in dentin)23  could not be proven by this trial. A longer follow-up could be required to validate these experimental strategies aiming to enhance the adhesive interface.

At 24 months, dentin pretreatment with EGCG did not provide any positive benefit in the clinical performance of the adhesive SU regardless of the bonding strategy used. In addition, including catechin placement prebonding results in an additional required step in the restorative procedure.

This investigation was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (CAPES) Finance Code 001 and (# PDSE 99999.006483/2015-01), from whom the first author received a scholarship. The authors also would like to thank the Central Analítica UFC/CT-INFRA/MCTI-SISNANO/Pró-Equipamentos CAPES for technical support.

Regulatory Statement

This study was conducted in accordance with all the provisions of the local human subjects oversight committee guidelines and policies of the Ethics Committee on Investigations involving human subjects of the Federal University of Ceará. The approval code issued for this study is 1.292.593.

Conflict of Interest

The authors of this article certify that they have no proprietary, financial, or other personal interest of any nature or kind in any product, service, and/or company that is presented in this article.

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Author notes

Cecília Atem Gonçalves de Araújo Costa, DDS, MSc, PhD, Graduate Program in Dentistry, Faculty of Pharmacy, Dentistry, and Nursing, Federal University of Ceará, Fortaleza, Brazil

Nadine Luísa Guimarães Albuquerque, DDS, MSc, PhD, Graduate Program in Dentistry, Faculty of Pharmacy, Dentistry, and Nursing, Federal University of Ceará, Fortaleza, Brazil

Juliano Sartori Mendonça, DDS, MSc, PhD, Department of Restorative Dentistry, Faculty of Pharmacy, Dentistry, and Nursing, Federal University of Ceará, Fortaleza, Brazil

Alessandro Dourado Loguercio, DDS, MSc, PhD, Department of Restorative Dentistry, School of Dentistry, State University of Ponta Grossa, Ponta Grossa, Brazil

Vicente de Paulo Aragão Saboia, DDS, MSc, PhD, Department of Restorative Dentistry, Faculty of Pharmacy, Dentistry, and Nursing, Federal University of Ceará, Fortaleza, Brazil

*Sérgio Lima Santiago, DDS, MS, PhD, Department of Restorative Dentistry, Faculty of Pharmacy, Dentistry, and Nursing, Federal University of Ceará, Fortaleza, Brazil