SEJ_2-2017_Articol_Ionescu

                    DENTAL MATERIALS
                    CALCIUM PHOSPHATE NANOPARTICLES REDUCE DENTIN HYPERSENSITIVITY:
Original Articles
                    A RANDOMIZED, PLACEBO-CONTROLLED SPLIT-MOUTH STUDY
                    Andrei C. Ionescu1a*, Elena M. Varoni2a, Gloria Cazzaniga1a, Marco Ottobelli1a, Eugenio Brambilla1b
                    1
                     Department of Biomedical, Surgical and Dental Sciences, IRCCS Galeazzi Orthopedic Institute, University of Milan, Via R. Galeazzi, 4, I-20161 Milan,
                    Italy
                    2
                     Department of Biomedical, Surgical and Dental Sciences, Dental Clinic ASST Santi Paolo e Carlo - Presidio Ospedaliero San Paolo, University of Milan,
                    Via Beldiletto, 1/3, I-20142 Milan, Italy

                    DDS, PhD
                    a

                    DDS, Professor
                    b

                                                                                                                                                                              Received: May 05, 2017
                                                                                                                                                                               Revised: May 29, 2017
                                                                                                                                                                             Accepted: June 13, 2017
                                                                                                                                                                             Published: June 14, 2017

                    Academic Editor: Nicoleta Ilie, Dipl-Eng, PhD, Professor, Department of Operative Dentistry and Periodontology, Faculty of Medicine,
                    Ludwig-Maximilians-Universität München, München, Germany

                    Cite this article:
                    Ionescu AC, Varoni EM, Cazzaniga G, Ottobelli M, Brambilla E. Calcium phosphate nanoparticles reduce dentin hypersensitivity: a randomized, placebo-
                    controlled study. Stoma Edu J. 2017;4(2):102-107.
                    ABSTRACT                                                                                                              DOI: 10.25241/stomaeduj.2017.4(2).art.2

                    Introduction: Modern strategies for dental remineralization and prevention of dentin hypersensitivity
                    are increasingly based on biomimetic materials. The aim of this study was to assess the clinical efficacy
                    of a calcium-phosphate nanoparticles-based dentin desensitizer (DD, Teethmate Desensitizer,
                    Kuraray Noritake, Japan).
                    Methodology: 25 patients, requesting treatment after reporting sensitivity of non-carious cervical
                    lesions and dental abrasions were recruited. Inclusion criteria were: response score ≥6 on a 10
                    cm-long visual analog scale (VAS) for 1+ teeth in each of two quadrants. Exclusion criteria were:
                    presence of systemic diseases, ongoing analgesic therapy, pregnancy, presence of carious or pulpal
                    lesions, poorly contoured restorations, enamel cracks, active periodontitis and ongoing use of
                    desensitizing agents. The response was determined to 2 s air blast. VAS scores were collected at t=0
                    (PRE), immediately after treatment with the DD (POST), after 1 week, and after 1, 3 and 6 months. Half
                    of the sites in each patient (split-mouth) were randomly treated with a placebo, and scores collected
                    until after 1 week. The DD was then applied to the placebo sites.
                    Results: Both DD and placebo significantly decreased VAS scores on POST confronted to PRE
                    (p<0.0001), showing similar efficacy (35% and 28%, respectively). DD application further decreased
                    scores after 1 week (63%) while placebo application did not show significant differences confronted
                    to POST (p=0.09). DD scores maintained throughout the observational period the levels obtained
                    after 1 week.
                    Conclusion: The tested DD effectively reduced dentin hypersensitivity during 6-month follow-
                    up, after one single application. Biomimetic desensitizers may be an effective solution to dentin
                    hypersensitivity.
                    Keywords: biomimetic material, dentin hypersensitivity, desensitization, calcium-phosphate
                    nanoparticles.

                    1. Introduction                                                                                     therefore decrease pain perception. Since this
                    A short pain on exposed dentin, which can be                                                        discovery, many therapeutic approaches to dentin
                    elicited by thermal, evaporative, tactile, osmotic                                                  hypersensitivity have been employed.1,2,4,6 Less
                    or chemical stimuli,1 characterizes dentinal                                                        recent techniques were based on blocking the
                    hypersensitivity. It is now widely acknowledged                                                     nociceptive conduction (mainly using potassium
                    that dentin hypersensitivity derives from exposed                                                   salts), on the superficial blocking of the orifices of
                    dentin tubules, where stimuli excite pulp cells                                                     the tubules with different compounds (varnishes,
                    as proposed by BrannstrÖm’s hydrodynamic                                                            dentin bonding systems), or by inducing sclerosis
                    theory.2,3 According to that theory, the diameter                                                   of the tubules (SnF2, SrCl*6H2O, Al-, K-, Fe- oxalate,
                    of the exposed tubules and their density are the                                                    Fluorides, Na2FPO4). Lasers are also employed
                    factors that mainly influence hypersensitivity,4 as                                                 and have obtained positive results, but the exact
                    already highlighted by Yoshiyama et al.5 Finding                                                    mechanism is not fully understood, being likely due
                    a way to close the orifices of the tubules could                                                    to either tubule occlusion or superficial glazing.6

                    *Corresponding author:
                    Dr Andrei C. Ionescu, DDS, PhD, Post-doc fellow and tutor
                    Department of Microbiology, Via Pascal, 36, First floor, 20133 Milan, Italy, Phone: +390250319007, Fax: +390250319040, e-mail: andrei.ionescu@unimi.it




 102                                                                                               Stoma Edu J. 2017;4(2): 102-107                                  http://www.stomaeduj.com
                            CALCIUM PHOSPHATE NANOPARTICLES REDUCE DENTIN HYPERSENSITIVITY:
                                                 A RANDOMIZED, PLACEBO-CONTROLLED STUDY

A new possibility is provided by the introduction of        eligible for this trial received extensive verbal and




                                                                                                                    Original Articles
biomimetic materials commonly used in dentistry.            written information regarding possible benefits
These materials can mimic a few properties of               and risks of the treatment. Patients were informed
the tissue they are replacing, and in particular the        that one of the compounds tested is a placebo
use of nanotechnologies can help in obtaining               and that, if they felt the treatment did not reduce
synthesis and precipitation of hydroxyapatite at            dentin hypersensitivity, they could feel free to exit
tooth level, opening possibilities for bioactive            the trial anytime and ask for alternative solutions.
compounds and biomaterials to remineralize                  2.2. Subject selection
tooth structures, modulate biofilm formation,               Patients visiting 3 different private practice
prevent caries occurrence and treat dentin                  dental offices in Northern Italy and requesting
hypersensitivity.7,8,9,10 Among several advantages          treatment after reporting sensitivity were screened
that these remineralization techniques present, the         for eligibility. Non-carious cervical lesions or
possibility of closing exposed orifices of dentinal         dental abrasions might be, or not, present at the
tubules using these materials is promising.                 hypersensitive sites. The inclusion criterion was a
The aim of this study was to assess the clinical            response score of ≥6 on a 10 cm long visual analog
efficacy, expressed as pain reduction from                  scale (VAS) that was numbered every centimeter
hypersensitive tooth areas, of a dentin desensitizer        from 0 to 10, for at least one tooth in each of two
(DD) based on calcium phosphate nanoparticles.              quadrants situated on the right-side and left-side
The null hypotheses were that (i) no differences            of the mouth, so that a split-mouth model for test
are shown between the tested DD and a placebo               and placebo compounds could be applied.
compound in pain reduction after one week of                Exclusion criteria were the presence of systemic
follow-up, and (ii) no significant differences in the       diseases, ongoing temporary or permanent
efficacy of the test compounds are found among              analgesic therapy for any reason, pregnancy,
the evaluated time points.                                  presence of carious or pulpal lesions, poorly
                                                            contoured restorations, presence of enamel cracks
2. Methods                                                  on the hypersensitive teeth, active periodontitis
2.1. Study design and materials                             and ongoing use of desensitizing agents of any
This study evaluated the efficacy of a calcium-             kind. Patients were also excluded if the clinical
phosphate nanoparticles-containing DD (test DD,             situation requested other treatments on the
Teethmate Desensitizer, Kuraray Noritake, Dental Inc.       screened sites than desensitizing alone.
Okayama, Japan) on desensitization of non-carious           The response was determined to a 2 s, cold air blast
cervical lesions and tooth abrasions. The test DD was       from a dental syringe directed perpendicularly
compared with a placebo during the first 1 week             to the tooth surface at approximately 5 mm
of evaluation in a trial designed as a randomized,          distance. In the VAS scale, patients were told that
double-blind, placebo-controlled, split-mouth study.        0 indicated a well-being condition with complete
After that period, only the test DD was evaluated to        absence of any pain, while 10 was the worst pain
assess its efficacy for up to 6 months. The composition     they experienced or thought could ever exist. VAS
of the materials used in this study are displayed in        scores collection was performed immediately after
Table 1; the powder and liquid were transferred from        the air blast, patients being asked to point on the
the original packaging to glass bottles only identified     VAS scale to the nearest full centimeter number
by letters, masking their content to both patient and       describing their pain perception.
dental operator (double-blind trial).                       A total of 25 patients were recruited, and each
The ‘Guidelines for the design and conduct of               had the hypersensitive sites assigned to test or
clinical trials on dentin hypersensitivity’ were            placebo treatment according to a randomization
adopted and partly followed during the design               list. Neither the patient nor the dentist performing
and execution of the study.11                               desensitizing treatments knew if the treated area
The study was conducted in agreement with the               belonged to the test or placebo compound, thus
principles of the Declaration of Helsinki updated           obtaining a double-blind model. The patients’
by the World Medical Association in 2013.12 Before          demographics were as follows: 9 males (32-57
obtaining written, informed consent, all patients           years old) and 16 females (25-60 years old).

 Table 1. Composition of the tested materials. Placebo was obtained using reagents purchased from Sigma–Aldrich
(St. Louis, MO, U.S.A.).

Material                               Powder                                   Liquid

Teethmate Desensitizer                 Tetracalcium phosphate, TTCP;            Ultrapure water
                                       dicalcium phosphate anhydrous,
                                       DCPA; sodium fluoride; glycerol;
                                       polyethylene glycol

Placebo                                Glycerol monostearate;                   HPLC-grade water
                                       polyethylene glycol (PEG3350)



Stomatology Edu Journal                                                                                              103
                    CALCIUM PHOSPHATE NANOPARTICLES REDUCE DENTIN HYPERSENSITIVITY:
                    A RANDOMIZED, PLACEBO-CONTROLLED STUDY

                    2.3. Application method                                         ordinal VAS scores), were not normally distributed
Original Articles   The targeted area was first cleaned with a cotton               and homoscedasticity was not respected, non-
                    pellet. Then, the dentist mixed the powder with                 parametrical    ANOVA      and    non-parametric
                    the liquid for 15 s to obtain a paste that was                  comparisons for each pair using Wilcoxon method
                    immediately applied on the treated areas with                   (p<0.05) were used to highlight significant
                    a microbrush by gently brushing for 2 min (Fig.                 differences between groups.
                    1 to 4). In the same visit, both test and placebo
                    treatments were applied to each patient according
                    to a randomization list. Patients were then asked
                    to rinse their mouth, and within 15 min after the
                    treatment the blinded dentist applied the same air
                    blast stimuli under the same conditions to assess
                    pain scores after treatments (POST). Patients were
                    recalled for hypersensitivity assessment of the
                    treated areas after 1 week. At that time point, after
                    data collection, both dentist and patients were un-
                    blinded regarding the test or placebo treatment,
                    and the test treatment was applied to the area                    Figure 3. Dental occlusal erosions bilaterally on palatal
                    that previously received the placebo compound.                  side of maxillary frontal and lateral teeth. Air blast test scored
                    Patients were then recalled after 1, 3 and 6 months             8. Patient was referred to a gastroenterologist physician. He
                    and at each recall the dentist assessed only tooth              was later diagnosed with gastroesophageal reflux disease
                                                                                    (GERD) and given treatment. Patient refused restorative
                    areas that were treated with test compound since                therapies, requesting treatment of pain symptoms only.
                    the beginning of the trial.




                                                                                     Figure 4. Application of the test DD on the same area as in Fig 3.
                      Figure 1. Patient requesting desensitization treatment for
                    vestibular areas of maxillary teeth. No presence of cervical
                    lesions or abrasions could be identified as well as other       3. Results
                    lesions, yet upper right and upper left canines and premolars
                    scored 7 on VAS after air blast test.
                                                                                    All 25 subjects completed the trial without requesting
                                                                                    alternative desensitization treatments or dropping
                                                                                    out from the trial. No adverse reactions were
                                                                                    reported. The results of the study are displayed in
                                                                                    Fig. 5. Both DD and placebo significantly decreased
                                                                                    VAS scores comparing POST and PRE (p<0.0001)
                                                                                    measurements, thus showing similar efficacy (35%
                                                                                    and 28%, respectively). DD application further
                                                                                    decreased scores after 1 week (63% in comparison
                                                                                    with PRE), while placebo application did not show
                                                                                    significant differences when compared to POST
                                                                                    (p=0.09). The scores from the areas treated with
                                                                                    the DD maintained, throughout the observational
                                                                                    period, the levels obtained after 1 week (maximum
                      Figure 2. Application of the tested DD on right maxillary     decrease in scores = 69% after 3 months). At 6
                    teeth (test site), same area depicted in Fig 1.                 months, a small, non-significant increase in VAS
                                                                                    scores was also observed.
                    2.3. Statistical analysis
                    All statistical analyses were performed using
                                                                                    4. Discussion
                    statistical software (JMP 10.0, SAS Institute Inc, Cary,
                                                                                    Dentin hypersensitivity is an increasing occurrence,
                    NC, USA). A preliminary check of the normality of
                                                                                    and dental materials or procedures able to reduce
                    distribution and homogeneity of variances was
                                                                                    the patient’s sensitivity are increasingly needed. A
                    performed using Shapiro-Wilk’s and Levène’s tests
                                                                                    variety of therapies are currently available,2,4,6 but
                    (p<0.0001 and p=0.0014, respectively). Since
                                                                                    the most modern and biocompatible approach
                    data did not belong to continuous variable (0-10



 104                                                                  Stoma Edu J. 2017;4(2): 102-107             http://www.stomaeduj.com
                                CALCIUM PHOSPHATE NANOPARTICLES REDUCE DENTIN HYPERSENSITIVITY:
                                                     A RANDOMIZED, PLACEBO-CONTROLLED STUDY

seems to be the one aiming at reconstituting                        layer with dentin surfaces, enhancing mineralization




                                                                                                                               Original Articles
a barrier and closing the open orifices of the                      under oral conditions.17 The data obtained in this
tubules by using biomimetic materials and                           study could convey some indirect hints regarding
techniques.13,14,15,16                                              the activity of the compound. It seems clear that the
                                                                    deposition of an amorphous layer of nanocrystals on
                                                                    the hypersensitive tooth surfaces does not lead to a
                                                                    reduction in pain perception greater than placebo
                                                                    effect. It is very likely, however, that hydroxyapatite
                                                                    and fluorapatite deposition inside dentinal tubules
                                                                    takes place at least over a one-week time period
                                                                    after application and is responsible for the significant
                                                                    reduction in pain perception when confronted to
                                                                    the placebo at 1 week or to the initial values. Our
                                                                    results confirm the assumptions of Zhou et al.10 thus
                                                                    providing a clinical confirmation of their in vitro
                                                                    results. In their study, the effectiveness of the same
                                                                    DD was evaluated in reducing dentin permeability
                                                                    and tubule orifice occlusion. It was found that the
                                                                    two parameters improved depending on the time
                                                                    until maximum values in permeability reduction
                                                                    and tubules occlusion were found after one week.10
                                                                    These results are in good correlation with those of
                                                                    the present study, meaning that dentine permeability
                                                                    and occlusion of tubuli orifices (>50%) can be good
 Figure 5. Box plot depicting the main findings of the study. The   indicators of reduction in pain perception.
minimum and maximum values and the 25th, 50th, and                  In our study, it was found that the reduction in
75th percentiles are shown in red. Different superscript letters    pain perception due to the test DD did not remain
indicate significant differences between groups (p<0.05) as         significantly different between the different time
assessed by Wilcoxon method. The test DD was compared with a        points starting from 1 week for up to 6 months. This
placebo for up to 1 week, then its effect on reducing pain
                                                                    means that the effects obtained by the tested DD
perception was monitored for 6 months.
                                                                    (remineralization, reduction in dentin permeability
                                                                    and tubule occlusion)10,17 are long-lasting, however
In this study, we assessed the clinical efficacy,
                                                                    additional studies are needed to ascertain if the test
expressed as pain reduction from hypersensitive
                                                                    DD may express its activity over extended observation
tooth areas, of a biomimetic, hydroxyapatite-forming
                                                                    times up to one or several years.
dentin desensitizer (DD) based on calcium phosphate
                                                                    The study was performed under conditions as
nanoparticles.
                                                                    close as possible with those of similar studies14,15 in
The first null hypothesis could not be fully rejected,
                                                                    order to evaluate possible differences yielded from
since immediately after application there was no
                                                                    geographical areas or pain perception. The tested
significant difference between DD under investigation
                                                                    DD compound was the same as the one used by
and placebo, meaning that the reaction to the test
                                                                    Mehta et al. in 201414 and similar to the one tested by
DD immediately after application could not be due
                                                                    the same research group one year after.15 The study
to its activity, but simply to a placebo effect. After
                                                                    design was the same as in Mehta et al., 2015,15 except
one week, however, there was a highly significant
                                                                    for the placebo follow-up that was stopped after 1
difference between placebo and test DD. In fact, the
                                                                    week in the present study. The statistical analysis was
test DD required 1 week to reach the significantly
                                                                    different in methodology, since in the present study
lowest scores of pain perception, and this level was
                                                                    no parametric analysis of data could be applied. One
maintained for up to 6 months. The second null
                                                                    would speculate that, given that the material, the
hypothesis could, therefore, be rejected.
                                                                    study design and the patient recruitment were very
The tested DD is a biomimetic desensitizing
                                                                    similar among these studies, similar results would be
compound based on the reaction between
                                                                    obtained. A first observation can be made comparing
tetracalcium phosphate and dicalcium phosphate
                                                                    the initial pain scores to those after treatment and
anhydrous in the presence of fluoride ions. Once
                                                                    1-week follow-up. The initial scores in the present
water is added, the reaction produces hydroxyapatite
                                                                    study were higher than those from Mehta et al.,14,15
and small parts of fluorapatite nanoparticles
                                                                    and reduction in pain perception after at least one
that precipitate as an amorphous layer on the
                                                                    week of treatment was higher than the results of
tooth structures. Since nanocrystal deposition on
                                                                    Mehta et al.,15 but similar to the results the same
enamel and dentin structures is driven by collagen
                                                                    Authors obtained one year earlier.14
backbone structures, one may speculate that the
                                                                    Many different explanations for these results may
presence of these structures inside dentine tubules
                                                                    be provided, including the fact that pain remains an
may help organize deposition of hydroxyapatite
                                                                    extremely subjective perception being influenced
and fluorapatite. Thanatvarakorn et al. in 201317
                                                                    by many confounding factors such as the socio-
provided some data in support of this hypothesis.
                                                                    economic-religious environment. This difference
They showed that the tested DD developed an
                                                                    shows the importance of performing several studies
immediate reduction in dentin permeability and an
                                                                    with different populations from as many different
effective integration of the calcium phosphate rich



Stomatology Edu Journal                                                                                                         105
                    CALCIUM PHOSPHATE NANOPARTICLES REDUCE DENTIN HYPERSENSITIVITY:
                    A RANDOMIZED, PLACEBO-CONTROLLED STUDY

                    environments as possible, particularly when testing                   longer than the minimum amount of time necessary
Original Articles   the clinical behavior of therapies influencing a                      to assess a difference between placebo and test (1
                    patient’s pain perception. From this point of view, the               week), since this would provide patients with further,
                    setting itself where the investigations were carried                  unnecessary discomfort.
                    out may be an additional confounding factor, since in                 Another difference in the study design regarded the
                    the present study it was constituted by some private                  assessment of hypersensitivity, since in the present
                    dental clinics while Mehta et al. evaluated patients                  study, contrary to Mehta et al.,14,15 it was decided not
                    seeking cure at a hospital Dental College.14,15 Apart                 to use the scrape test. The guidelines on conducting
                    from the aforementioned factors, this distinction                     trials on dentin hypersensitivity suggested, as an
                    may have had an influence on the general health                       example of response-based method, the use of cold
                    expectations patients had.                                            stimuli, such as timed air blast, or tactile stimuli.11 In
                    An additional difference between our study and that                   the study conducted by Mehta et al, as well as in many
                    of Metha et al.15 is that the latter evaluated Teethmate              other studies, response was evaluated using both
                    AP paste, produced by the same manufacturer as                        air blast and the tactile running of a dental explorer
                    the desensitizer tested here. The main difference                     across the cervical area of the assigned teeth, in
                    between the two products is that the paste is a water-                horizontal and vertical direction at a “relatively mild
                    free calcium phosphate compound, while the test DD                    force”. If one considers the microscopical and sub-
                    used in this study is a mixture of calcium phosphate                  microscopical structure of enamel and dentine,
                    powder with water, containing an accelerator that                     however, it is clear that the tactile test is invasive and
                    leads upon mixture and application to the reaction                    may produce damage to tooth structures at that level.
                    producing      and      precipitating      hydroxyapatite             Furthermore, tactile tests, if applied immediately after
                    nanocrystals.18 Comparing all findings, the pain                      desensitization, may locally disturb the precipitated
                    reduction obtained by the paste desensitizer was                      layer of nanocrystallites, hampering their further
                    slower and more moderate than that of the DD tested                   deposition and organization to occlude dentin tubule
                    in this study.                                                        orifices. For this reason, any contact test was avoided
                    According to Holland et al.,11 assessments were                       in the present study, and further studies may be
                    made between contralateral teeth, and one side                        performed to assess the influence of tactile stimuli on
                    of the mouth served as a control for the other side                   the behavior of biomimetic hydroxyapatite-forming
                    (split-mouth model). A randomization list was                         dentin desensitizers.
                    used to assign each side to either test or control
                    treatments. The comparisons were made between                         5. Conclusion
                    an active treatment (test DD) and a placebo that                      The results obtained in this study showed that the
                    had aspect and composition identical to the active                    tested DD effectively reduced patient discomfort
                    treatment, save for the active principles. In a previous              caused by dentin hypersensitivity during a 6-month
                    study15comparisons were made between a similar                        follow-up, up to 69% after 3 months, after one single
                    DD and distilled water (placebo) for up to 6 months.                  application. Biomimetic, hydroxyapatite-forming
                    In a pilot study we performed on 3 patients (data not                 desensitizers may be an effective solution to dentin
                    shown), we saw that differences between placebo                       hypersensitivity.
                    and test compounds were noticeable as of 1 week
                    after treatment. It must be noted that all enrolled                   Disclosure
                    patients of this study reported discomfort levels in                  No conflict of interest exists for any of the Authors of
                    response to air blast ≥6 on VAS scale, and the tested                 the paper.
                    treatment aimed to reduce pain perception. Contrary                   This research did not receive any specific grant from
                    to the study design adopted by Mehta et al.,15 in                     funding agencies in the public, commercial, or not-
                    the present study it was therefore decided not to                     for-profit sectors.
                    prosecute observations on the placebo group for
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 106                                                                       Stoma Edu J. 2017;4(2): 102-107. http://www.stomaeduj.com
                                CALCIUM PHOSPHATE NANOPARTICLES REDUCE DENTIN HYPERSENSITIVITY:
                                                     A RANDOMIZED, PLACEBO-CONTROLLED STUDY

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                                                                           Andrei Cristian IONESCU
                                                            DDS, PhD, Post-doc fellow and tutor
                                          Department of Biomedical, Surgical and Dental Sciences
                                                            IRCCS Galeazzi Orthopedic Institute
                                                                  University of Milan, Milan, Italy


CV
He graduated with top marks in Dentistry and Oral Prosthetic Rehabilitation at the University of Milan, Italy, in
2008. He got his PhD in Nanotechnologies at the University of Trieste, Italy, in 2015. Since 2005 he has been
working at the Oral Microbiology Laboratory of the University of Milan, director Prof. Eugenio Brambilla, where
he has been a research coordinator as of 2013. He authored 25 publications in peer-reviewed journals. He
won the Paffenbarger Award of the Academy of Dental Materials, the Robert Frank Award of the Continental
European Division, International Association of Dental Research (CED-IADR) and the Espertise contest of
3M Oral Care. He is a promoter of the Young Researchers Group of CED-IADR. His main research interests
include the study of bioactive and biomimetic materials, antimicrobial compounds and their interactions with
oral biofilms.



Questions
What is a biomimetic material?
qa. A material that is only made of biological parts taken from natural tissues;
qb. A material able to reproduce some features and properties of a natural tissue;
qc. A material that reacts with the environment in a different way than a natural tissue does;
qd. A material that does not react in any way with the environment or with the host.

Which one cannot be the mechanism of action of a dentin desensitizer?
qa. It can block pain stimuli by blocking nervous transmission, for instance using potassium salts;
qb. It can demineralize dentin surface, thus leaving more tubule orifices open to the oral environment;
qc. It can cause sclerosis of the tubuli, thus reducing their lumen until the tubule is closed;
qd. It can cause deposition of crystals inside tubuli, thus closing their orifices.

Which of these factors must be exclusion factors for subject recruitment when conducting a
trial on dentin sensitivity?
qa. Subjects already using a desensitizing toothpaste;
qb. Subjects permanently using analgesic therapies;
qc. Subjects younger than 30;
qd. Subjects presenting carious lesions.

If a test treatment shows a positive effect confronted to the baseline, but the effect is non-
significantly different from that of a placebo, what conclusions can be drawn?
qa. The test compound is performing better than the placebo;
qb. The test compound is not safely applicable to human subjects;
qc. The test compound does not perform better than the placebo;
qd. The placebo effect is not visible in the test.



Stomatology Edu Journal                                                                                                                107