Article_6_1_3

                   ADHESIVE DENTISTRY
                   INFLUENCE OF FLUORIDE MOUTHWASH CONTAINING NANOHYDROXYAPATITE ON
Original Article
                   THE DENTIN INTERFACE OF DIRECT RESTORATIONS: A RANDOMIZED CONTROLLED
                   CROSSOVER IN SITU STUDY
                   Dayane Carvalho Ramos Salles de Oliveira1a* , Livia Rodrigues de Menezes2a , Lúcia Trazzi Prieto1a ,
                   Erick Kamiya Coppini1b , Luís Alexandre Maffei Sartini Paulillo1c , Gisele Damiana da Silveira Pereira2c
                   1Department of Restorative Dentistry, Piracicaba Dental School, State University of Campinas, Piracicaba, SP, Brazil
                   2
                    Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

                   a
                     PhD, Assistant Professor
                   b
                     PhD
                   c
                    PhD, Associate Professor

                   ABSTRACT                          DOI: https://doi.org/10.25241/stomaeduj.2019.6(1).art.3

                   Introduction: To evaluate the influence of a fluoride mouthwash containing                                                       OPEN ACCESS This is an Open
                                                                                                                                                    Access article under the CC BY-NC
                   nanohydroxyapatite on the dentin bonding interface microhardness of direct resin                                                 4.0 license.
                   composite restorations in situ.
                   Methodology: Forty human premolars were sectioned and restored with a three-step                                                  Peer-Reviewed Article

                   adhesive system or a self-etch adhesive system and a conventional resin-based composite.                                     Citation: de Oliveira DCRS, de Menezes LR,
                   After the initial microhardness measurements on the samples’ dentin interface, the                                           Prieto LT, Coppini EK, Sartini Paulillo LAM,
                                                                                                                                                da Silveira Pereira GD. Influence of fluoride
                   restored samples were fixed in acrylic palate appliances for an in situ experiment. Ten                                      mouthwash containing nanohydroxyapatite
                                                                                                                                                on the dentin interface of direct restorations:
                   volunteers participated in a randomized double-blinded crossover study using the palate                                      a randomized controlled crossover in situ
                   appliances and a placebo fluoride mouthwash for one week, one-week wash-out, and                                             study. Stoma Edu J. 2019;6(1):24-28

                   one-week fluoride mouthwash containing nanohydroxyapatite. The final microhardness                                           Received: February 09, 2019
                   measurements were evaluated, and data were analyzed by ANOVA and Tukey’s test                                                Revised: February 28, 2019
                                                                                                                                                Accepted: March 18, 2019
                   submitted for multiple comparisons (α = 0.05; 0.8 power).                                                                    Published: March 19, 2019
                   Results: There were statistically significant differences between the mouthwash
                                                                                                                                                *Corresponding author:
                   treatments with both adhesive systems tested (p < 0.001). The nanohydroxyapatite used                                        Dayane C.R.S. de Oliveira
                   in the mouthwash was an influencing factor on the dentin interface microhardness of                                          Department of Restorative Dentistry,
                                                                                                                                                Piracicaba Dental School
                   resin composite restorations.                                                                                                State University of Campinas, 901, Limeira
                   Conclusion: The fluoride mouthwash containing the nanohydroxyapatite was able to                                             Ave.SP-13414-903 Piracicaba, Brazil
                                                                                                                                                Tel / Fax: +55 (019) 2106-5341
                   increase the dentin microhardness of the direct resin composite restorations regardless                                      e-mail: dayoli87@gmail.com
                   of the adhesive system used.                                                                                                 Copyright: © 2019 the Editorial Council
                   Keywords: Dental materials; composite resins; dental adhesive; mouthwashes.                                                  for the Stomatology Edu Journal.



                   1. Introduction                                                                   enables the infiltration of various harmful agents, as
                   Dental enamel etching increases the surface energy,                               well as oral fluids, to infiltrate these gaps. Therefore,
                   which facilitates the penetration of the adhesive                                 ions, such as calcium and fluoride, present in saliva or
                   system and the adhesion to this substrate [1]. Adhesion                           solutions used as mouthwashes [4] can also penetrate
                   to the enamel substrate is more efficient than to the                             and fill the micro porosity present in the hybrid layer,
                   dentin substrate since it is composed of an inorganic                             thus decreasing its permeability [8-10]. It becomes
                   matrix, while dentin presents a more significant                                  evident that evaluating whether or not the use of
                   amount of organic matrix composed mainly of                                       mineralizing agents allows adducing within the hybrid
                   collagen and water [2]. Moisture control, maintenance                             layer of ions that can fill the nanopores present in the
                   of the permeable collagen to the adhesive system                                  dentin interface is essential. Thus, this study assessed
                   penetration, and demineralization of acid etching are                             the influence of a fluoride mouthwash containing
                   essential factors to improve the transition zone, called                          nanohydroxyapatite on the dentin bonding interface
                   the hybrid layer [3], which is the primary mechanism                              microhardness of direct resin composite restorations.
                   of adhesion to the dentin substrate [4]. Several                                  The null hypothesis was that the use of the fluoride
                   factors can influence the hybrid layer development.                               mouthwash containing nanohydroxyapatite will not
                   When moisture control is performed incorrectly, the                               influence the dentin interface microhardness of direct
                   penetration of the monomers into the demineralized                                resin composite resin restorations.
                   dentin is incomplete, resulting in failure areas. This
                   increases the risk of nanoleakage through the pores
                   present in the adhesive interface of this defective                               2. Methodology
                   hybrid layer. It can cause postoperative sensitivity and                          2.1. Ethical aspects
                   reduce the longevity of the direct restorations [5,6].                            This in situ, double-blinded, single center, randomized
                   The presence of failure areas on the adhesive interface                           controlled crossover study was authorized by the




   24                                                                              Stoma Edu J. 2019;6(1): 24-28.                         http://www.stomaeduj.com
    INFLUENCE OF FLUORIDE MOUTHWASH CONTAINING NANOHYDROXYAPATITE ON THE DENTIN INTERFACE OF
                           DIRECT RESTORATIONS: A RANDOMIZED CONTROLLED CROSSOVER IN SITU STUDY




                                                                                                                                         Original Article
 Figure 1. Flow diagram with a systematic illustration of the crossover in situ model and experimental design.

local Institutional Ethics Committee of the Piracicaba                       UNICAMP, Piracicaba, SP, Brazil. For the three-step
Dental School, Piracicaba, SP, Brazil (protocol                              adhesive system, the excess water was removed by
#149/2012). A written informed consent was obtained                          capillary action with an absorbent paper. The dentin
from all volunteers in the study. Volunteers had the                         etching was performed with 35% phosphoric acid for
right to withdraw from the study at any time and for                         15 s, followed by rinsing with abundant water for 30 s.
any reason without prejudice.                                                The moisture was controlled with a moist cotton ball.
                                                                             Both adhesive systems were used according to the
2.2. Preparation of the specimens                                            manufacturers’ instructions with a microbrush and
Forty human premolars recently extracted because of                          light cured for 20 s with a LED light source (Radii, SDI,
orthodontic reasons were donated to this study. The                          Victoria, Australia). The restoration was carried out
teeth were stored for 24 h in a 0.1% thymol solution at                      with a single 2 mm increment of the resin composite
37°C, then stored in distilled water until the beginning                     in a 4 x 4 mm acetate pattern to standardize the direct
of the study. The coronal portion was separated from                         restorations, and then light-cured for 20 s. All samples
the root through a straight section on the long axis                         were stored in 100% relative humidity at 37°C for 24 h.
of the tooth using a metallographic precision cutter
(Isomet 1000, Buehler Ltd., Buff Lake, IL, USA) with a                       2.3. In situ study
diamond saw under constant irrigation. To obtain a                           This in situ, double-blinded, single center,
flat dentin surface, the occlusal surfaces were ground                       randomized controlled crossover study was carried
with sandpaper silicon carbide (SiC) #320 and #400 in                        out for three weeks, including a one-week fluoride
a metallographic polisher sander cooled with water.                          nanohydroxyapatite-free phase, a one-week washout
Then, 4 x 4 mm dentin blocks were obtained with 2 mm                         period and a one-week fluoride nanohydroxyapatite-
of thickness. After an ultrasound bath to remove the                         active phase. A total of 10 adult volunteers (mean age
sander debris, the standardization of the smear layer                        23.3 ± 2.3 yrs; 5 females and 5 males) were recruited
was performed on the dentin flat by manually rubbing                         in the Piracicaba Dental School, UNICAMP, Piracicaba,
with SiC wet sandpaper #1000 and #1200 for 15 s per                          SP, Brazil and in the Dental School of the Federal
sandpaper grit. The dentin blocks were kept in 100%                          University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
relative humidity at 37°C. This study used the total                         All volunteers had confirmed satisfactory oral health,
etching technique with a three-step adhesive system                          did not use any medication, did not have any systemic
(Scotchbond Multi-Purpose Plus, 3M ESPE, St. Paul,                           disease or pregnancy, and did not use any mouthwash
MN, USA) and a self-etch adhesive system (Clearfill SE                       or toothpaste except as provided for the research.
Bond, Kuraray, Tokyo, Japan) with a nanofilled resin                         In this study, all volunteers completed the study,
composite (Filtek Z350 XT, 3M ESPE, St. Paul, MN, USA).                      no participants were excluded or withdrawn from
All clinical and laboratory steps were performed at the                      the study. Impressions of all the volunteers’ mouths
Restorative Department of Piracicaba Dental School,                          were made to obtain a model to make a palate acrylic



Stomatology Edu Journal                                                                                                                     25
                   INFLUENCE OF FLUORIDE MOUTHWASH CONTAINING NANOHYDROXYAPATITE ON THE DENTIN INTERFACE OF
                   DIRECT RESTORATIONS: A RANDOMIZED CONTROLLED CROSSOVER IN SITU STUDY

Original Article    Table 1. Means (standard deviations) values for microhadness test (KHN).

                                                                                                                   Microhardness
                                        Experimental Group
                                                                                                         Initial                          Final
                    Clearfill SE (+ testing mouthwash)                                               42.59 (0.5) Ba                  44.33 (0.6) Aa
                    Clearfill SE (+ placebo mouthwash)                                               41.29 (0.5) Aa                  40.4 (1.0) Ab
                    ScotchBond MP (+ testing mouthwash)                                              42.15 (0.4) Bb                  45.42 (0.6) Aa
                    ScotchBond MP (+ placebo mouthwash)                                             39.66 (0.6) Aab                  40.35 (0.5) Ab
                   *Means followed by different capital letters in the same line and small letters in the same column were significantly different (p < 0.05).

                   appliance for the upper arch. In each plate two cavity                      their teeth using the same toothpaste containing no
                   sites were fabricated where the specimens were fixed.                       fluoride during all study. The volunteers should wear
                   All sites were positioned posterior to the incisive                         the appliance for more than 20 h per day, removing
                   papillae to avoid contact between the tongue and                            it only while eating or brushing. The volunteers were
                   the specimens. Every site had a 4.5 x 4.5 mm uniform                        instructed to rinse off their appliance and store it in
                   gap with 4 mm in depth covered by a plastic mesh                            artificial saliva while not in use.
                   to allow free contact of the saliva with the specimens,
                   but protection from mechanical disturbance. New                             2.4. Microhardness readings (KHN)
                   specimens were inserted into the appliance before                           The Knoop Microhardness of the dentin interface
                   phase 2. The specimens were randomly assorted and                           (illustrated in Fig. 1) was examined using a
                   allocated into two groups: experimental or placebo. A                       microhardness tester (HMV-2, Shimadzu, Kyoto,
                   systematic illustration of the crossover in situ model                      Japan) with a 50 g load for 15 s in three equally spaced
                   and the experimental design can be observed in                              points on each sample. A blinded trained operator
                   Fig. 1. In the first week half of the volunteers were                       performed all the microhardness measurements
                   randomly allocated to use the fluoride mouthwash                            before and after the crossover in situ experiment. The
                   containing nanohydroxyapatite, while the other half                         microhardness of each sample was taken from the
                   to use the placebo fluoride mouthwash containing                            arithmetic mean of the three readings.
                   no nanohydroxyapatite. After the second week
                   “wash-out” to neutralize the fluoride agent and the                         2.5. Statistical analyses
                   microhardness readings, the groups were reversed                            The sample size was calculated according to a
                   and conducted as described in the first week. The                           pilot test to provide a power of 0.8. The power was
                   volunteers who used the placebo fluoride mouthwash                          calculated according to power analysis. The data were
                   in the first week used the tested mouthwash in the                          subjected to ANOVA and Tukey’s test with a limit of
                   second week and vice versa. The study products and                          5% probability of making decisions.
                   tested materials were provided as coded packages
                   labeled with participants number and study period.
                   None of the volunteers, in situ study instructors or                        3. Results
                   in situ study monitors that were participating in the                       ANOVA showed a significant difference between
                   study knew the type of group (placebo or test) being                        the tested groups (placebo/tested mouthwash x
                   tested until all procedures were finalized. The in situ                     time) (p < 0.001). Mean values taken from Tukey’s
                   study coordinators were responsible for blinding                            test are shown in Table 1. As could be observed,
                   all participants and labeling the study products and                        the nanohydroxyapatite used in the mouthwash
                   tested materials. The mouthwashes used in the study                         was an influencing factor on the dentin interface
                   were prepared by FGM Produtos Odontológicos                                 microhardness of resin composite restorations.
                   (89219-501 Joinville, SC, Brasil). The placebo fluoride                     The     fluoride   mouthwash       containing    the
                   mouthwashes were produced with the same                                     nanohydroxyapatite managed to increase the dentin
                   color, viscosity and taste compared to the tested                           interface microhardness of direct resin composite
                   mouthwash. The placebo mouthwash and the tested                             restorations regardless of the adhesive system used,
                   one contained the same components, including the                            while the placebo fluoride mouthwash solution
                   fluoride and the potassium nitrate, but only the tested                     containing no nanohydroxyapatite had no influence
                   mouthwash contained the nanohydroxyapatite,                                 on dentin interface microhardness.
                   as in the Desensibilize Nano P (FGM Produtos
                   Odontológicos, 89219-501 Joinville, SC, Brasil). The
                   volunteers were instructed to swish 20 mL of the                            4. Discussion
                   mouthwash around their mouth for thirty seconds                             The present study clinically investigated the
                   then spit it out with no rinsing. The volunteers were                       influence of a fluoride mouthwash containing
                   also instructed to use it twice a day, every day, after                     nanohydroxyapatite on the dentin bonding interface
                   brushing and flossing their teeth in the morning                            microhardness of direct resin composite restorations
                   and at night. All volunteers were instructed to brush                       in situ. There are several in vitro studies showing



   26                                                                       Stoma Edu J. 2019;6(1): 24-28.               http://www.stomaeduj.com
   INFLUENCE OF FLUORIDE MOUTHWASH CONTAINING NANOHYDROXYAPATITE ON THE DENTIN INTERFACE OF
                          DIRECT RESTORATIONS: A RANDOMIZED CONTROLLED CROSSOVER IN SITU STUDY


possible effects of mouthwashes in composite                  should be performed to further evaluate the clinical




                                                                                                                                  Original Article
restorations overtime [11-14]. However, there is no           performance of these different treatments using
consensus about this topic, and the reason for this           mouthwashes and their real effects in the long term.
is that different mouthwashes contain different               By all means, the addition of nanohydroxyapatite
components. The crossover in situ model allowed to            seems to increase the efficiency of fluoride with
access the real effects in the oral cavity. Moreover, the     regard to mineralization. The remineralizing formula
use of the same fluoride mouthwash composition                containing nanostructured calcium phosphate,
varying only the addition or not of nanohydroxyapatite,       organized in the crystalline form of hydroxyapatite
allowed to access the real influence of the different         allows the releasing of calcium and phosphate ions
mineralizing agents on the dentin bond interface              to the demineralized surface of the tooth, which
of composite restorations. The null hypothesis that           can be reorganized in the form of hydroxyapatite,
the use of the fluoride mouthwash containing                  fluorapatite or calcium fluoride, as well as to occlude
nanohydroxyapatite would not influence the dentin             the dentinal tubules. Moreover, the hydroxyapatite
interface microhardness of direct resin composite             crystals are highly stable and more resistant to acidic
resin restorations was rejected. This occurred since          challenges when compared to amorphous calcium
the final microhardness values were statistically             phosphates, explaining the increased efficiency of
different between the fluoride mouthwash containing           the tested formula containing nanohydroxyapatite
nanohydroxyapatite and the placebo fluoride                   in comparison to the fluoride placebo formula. Thus,
mouthwash containing no nanohydroxyapatite,                   with the limitations of this crossover in situ study, it
regardless of the adhesive system tested. The                 was possible to conclude that the fluoride mouthwash
mineralizing agents had been tested to reduce the             containing nanohydroxyapatite managed to increase
failure areas of the adhesive interface, hindering the        the dentin microhardness of direct resin composite
infiltration of harmful agents. Calcium and fluoride          restorations regardless of the adhesive system used
have been described in the literature as being able           within one week. On the other hand, the conventional
to fill the microporosity present in the hybrid layer,        fluoride mouthwash solution had no influence on
decreasing its permeability [7-10]. As observed               dentin microhardness within one week.
in this study, the fluoride mouthwash containing
nanohydroxyapatite managed to influence the
dentin microhardness showing a possible ability to            Authors contribution
fill the microporosity present in the dentin interface.       DO/LM: Experimental design, crossover in situ
However, due to the similar mean values of the initial        study coordinator, statistical analysis, manuscript
and final microhardness, it is presumed that despite          writing, manuscript proofreading. LTP: Experimental
the capability of the fluoride to penetrate the hybrid        design, blinded in situ study clinical instructor,
layer, it could have been lixiviated from the hybrid          manuscript proofreading. EK: Experimental design,
layer during the in situ study, not contributing to filling   blinded technical microhardness tester, manuscript
the microporosities present in the dentin interface.          proofreading. GP/LMP: Experimental design, in situ
The microporosities in the dentin interface occurs            study clinical monitor, manuscript proofreading.
due to the incorrect or incomplete penetration of the
adhesive monomers into the demineralized dentin,
resulting in failure areas within the hybrid layer. These     Acknowledgments
failures within the hybrid layer increase the risk of         This study thanks FGM for preparing and donating the
micro or nanoleakage through the pores present in             mouthwashes used in this study. DO is a Post-Doctoral
the adhesive interface, reducing the longevity of the         Researcher at the Sao Paulo Research Foundation
restoration [5-6]. However, the same way oral fluids          (FAPESP grant #2016/05823-3 and #2017/22161-7).
can infiltrate through these failures, other substances       The authors declare no potential conflict of interest
such as calcium and fluoride, present in the saliva           concerning the authorship or the publication of this
or solutions used as mouthwashes [4] could also               article.
penetrate and fill the microporosity present in the
hybrid layer, thus decreasing its permeability [8-10],
and possibly increasing the longevity of composite            References
restorations. As observed in this study, despite fluoride     1.   Buonocore MG. A simple method of increasing the adhesion
having been described in the literature as being                   of acrylic filling materials to enamel surfaces. J Dent Res.
                                                                   1955;34(6):834-853.
able to fill the microporosity present in the hybrid               [CrossRef] [PubMed] Google Scholar Scopus
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                                                                   Dent. 2000;79(4):29-33.
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Stomatology Edu Journal                                                                                                              27
                   INFLUENCE OF FLUORIDE MOUTHWASH CONTAINING NANOHYDROXYAPATITE ON THE DENTIN INTERFACE OF
                   DIRECT RESTORATIONS: A RANDOMIZED CONTROLLED CROSSOVER IN SITU STUDY

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                         across the resin-dentin interface: in vivo evaluation with     13.   Yap AU, Tan BW, Tay LC, et al. Effect of mouthrinses on
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                                                                                          Dayane C. R. S. de OLIVEIRA
                                                                                            DDS, MS, PhD, Assistant Professor
                                                                 Department of Restorative Dentistry Piracicaba Dental School
                                                                                                State University of Campinas
                                                                                                          Piracicaba, SP, Brazil


                   CV
                   Dayane C. R. S. de Oliveira, DDS, MS, PhD, is a post-doc fellow of the Department of Restorative Dentistry at Piracicaba Dental
                   School, State University of Campinas (UNICAMP), in Brazil. Dr. Oliveira is a young researcher that contributed to 6 textbook
                   chapters, authored 7 patents and is the recipient of many awards in her area of expertise. Her areas of interest include esthetic
                   dentistry, color science and biomaterials development and characterization.



                   Questions
                   1. Based on the results in this study, fluoride mouthwashes:
                   qa. Are capable of increasing microhardness of dentin interface of composite restorations;
                   qb. Are not capable of increasing microhardness of dentin interface of composite restorations;
                   qc. Are not necessarily capable of increasing microhardness of dentin interface of composite restorations
                   depending on composition;
                   qd. None of the above.

                   2. Based on the results in this study, fluoride mouthwashes containing
                   nanohydroxyapatite:
                   qa. Are capable of increasing microhardness of dentin interface of composite restorations;
                   qb. Are not capable of increasing microhardness of dentin interface of composite restorations;
                   qc. Have similar performance compared to conventional fluoride mouthwashes;
                   qd. None of the above.

                   3. Based on the discussion section, which statement is true:
                   qa. Fluoride mouthwashes not containing nanohydroxyapatite might be capable of infiltrating in the hybrid
                   layer and forming amorphous calcium phosphates; but it is probably dissolved and lixiviated over time;
                   qb. Fluoride mouthwashes not containing nanohydroxyapatite do not contribute to filling the microporosities
                   present in the dentin interface over time;
                   qc. Fluoride mouthwashes containing nanohydroxyapatite are capable of infiltrating in the hybrid layer, and
                   forming highly stable hydroxyapatite crystals;
                   qd. All of the above.

                   4. Based on the discussion section, which statement is not true:
                   qa. The primary limitation of this study was follow-up time which does not allow the authors to extrapolate the
                   results in regard the longevity of the composite restorations;
                   qb. Literature demonstrate the immediate results of fluoride agents, however, this study demonstrated that
                   these results can be modified over time;
                   qc. This study demonstrated that increasing the longevity of the composite restorations might be possible
                   using fluoride agents associated with nanohydroxyapatite, however further studies are necessary;
                   qd. None of the above.



   28                                                                     Stoma Edu J. 2019;6(1): 24-28.                http://www.stomaeduj.com