Restaurações Protéticas Fixas e Saúde Periodontal - Narrativa 1
Restaurações Protéticas Fixas e Saúde Periodontal - Narrativa 1
Restaurações Protéticas Fixas e Saúde Periodontal - Narrativa 1
Functional
Biomaterials
Review
Fixed Prosthetic Restorations and Periodontal Health: A
Narrative Review
Viritpon Srimaneepong 1 , Artak Heboyan 2, * , Muhammad Sohail Zafar 3,4 , Zohaib Khurshid 5 ,
Anand Marya 6,7 , Gustavo V. O. Fernandes 8 and Dinesh Rokaya 9, *
1. Introduction
Proper treatment planning and prosthetic treatment are essential for the long-term
outcome of prosthetic dental treatment. There is a strong association between prosthetic
dentistry and periodontics as periodontal health has an important role in the longevity of
fixed dental restorations [1–3]. On the other hand, defective prostheses may contribute to
the progression of periodontal diseases [4]. The final finish of the prosthetic restoration
also affects the development of biofilm, as increased surface roughness creates a favorable
environment for microbial growth. Hence, a good prosthesis surface finish from proper
manufacturing technique is important [5]. To achieve a successful treatment outcome,
prosthodontists and periodontists should collaborate, to enhance the longevity of the
restoration and improve periodontal health, as well as improve the quality of life for dental
patients [3,6].
Morpho-functional impairments of the maxillofacial complex conditioned by peri-
odontal pathology are five times more common compared with those arising from dental
caries [7]. Periodontitis is an inflammatory disease involving the periodontal tissues (ce-
mentum, periodontal ligament, alveolar bone, and gingiva) supporting the teeth [8]. It
results in teeth loss requiring prosthetic treatment. A delay in prosthetic treatment causes
biomechanical impairment of the stomatognathic system, worsening of the periodontal
condition, and adverse consequences on the patients’ general health and behavior [9–12].
Prosthetic treatment receives special attention in the case of patients with periodontal
pathology [13,14]. However, sometimes, inappropriate prosthetic treatment planning or
the prosthesis itself can cause periodontitis or gingival recession and associated clinical
characteristics (Figure 1).
Figure 1. The clinical characteristics of periodontal inflammation. GCF = gingival crevicular fluid;
PMNs = polymorphonuclear leukocytes.
The aim of this article is to review and present the current knowledge regarding the
various technical, clinical, and molecular aspects of different prosthetic biomaterials and
highlight the interactions between periodontal health and prosthetic restorations.
J. Funct. Biomater. 2022, 13, 15 3 of 21
Figure 2. Good marginal fit of the crown and a poor marginal fit leading to consequences.
Although no substantial difference was seen in the internal precision in the computer-
aided design and computer-aided manufacturing (CAD/CAM) restorations [22], it has been
J. Funct. Biomater. 2022, 13, 15 4 of 21
The esthetics and longevity of the prosthesis are conditioned by the harmony and
biofunctionality between the prosthetic construction and the periodontium [3]. The biofunc-
tionality of a prosthesis refers to a function that is dependent on biological content. The life
span of fixed prosthetic constructions depends on the periodontal status of the supporting
teeth, since the mucosa in this region is subject to continuous mechanical trauma and
J. Funct. Biomater. 2022, 13, 15 5 of 21
bacterial contamination [33,34]. Thus, numerous factors, such as the condition of abutment
teeth, pontic design, prosthesis construction, occlusion, and biomaterial have tangible
influence and should be considered when planning the prosthodontic treatment [35]. The
preservation of periodontal health around the crown’s margins is a serious challenge for a
dentist, and detecting the restoration margin relative to the neighboring bone is a signifi-
cant factor when providing for the long-lasting health of the gingival tissues [36,37]. The
emerging couture of the prosthetic construction can affect the gingiva reaction to the fixed
prosthesis. Moreover, the life span of fixed dental restorations is governed by the margin
adaptation of the prostheses [15].
An incorrectly fabricated dental prostheses construction may harm both the health
of the oral tissues and worsen any existing periodontal pathology. Rough and irregular
surfaces on the restorative biomaterials may create a favorable environment for microbial
invasion and biofilm formation [38–40]. Any rough and irregular margins on the fixed
prosthetic constructions can also result in microorganisms’ attachment. The aforementioned
factors can worsen oral hygiene conditions and cause gingivitis and further periodonti-
tis. Zirconia surface relief alterations and roughness following the application of laser
irradiation were studied by Popa et al. [41]. The group Nd:YAG consists of zirconia restora-
tions treated with a neodymium laser and the group Er:YAG included restorations treated
with an erbium laser. The authors noted that there were substantial differences between
the Nd:YAG and Er:YAG following surface irradiations. The Nd:YAG laser shaped more
changes in the zirconia surface than the Er:YAG. Thus, poor oral hygiene was detected
in 35% of the patients with conventionally fabricated metal–ceramic dental prostheses, in
30.3% of the subjects with CAD/CAM fabricated metal–ceramic prostheses, and 28.6% of
the patients with zirconia-based ceramic prostheses, one year after the insertion of the con-
structions [42]. In addition, fixed prosthetic restorations, such as crowns and bridges may
interfere with the host’s defensive mechanisms creating regions of microbial colonization
and resulting in bacterial biofilm formation, which subsequently damages the periodontal
tissues [43].
index score, plaque index, and sulcus bleeding index scores. They found that the lingual
surfaces showed the highest probability of plaque compared to the facial surfaces. The
risk of gingival bleeding at the posterior crown margins was approximately twice that
seen at the supragingival margins. Poor oral hygiene before treatment and the presence
of plaque were also associated with sulcular bleeding. The type of alloy did not influence
sulcular bleeding. The probability of plaque at 1 year increased with an increasing oral
hygiene index score before treatment. In addition, Ercoli and Caton [51] mentioned that
the restoration margins placement within the junctional epithelium and supracrestal con-
nective tissue attachment can be associated with gingival inflammation and, potentially,
recession [51]. The presence of the fixed prostheses finish lines within the gingival sulcus
does not cause gingivitis if the patients are compliant with self-performed plaque control
and periodic maintenance.
The gingival morphology is partially related to the tooth form and shape. Tooth
shapes can be square, triangular, or ovoid [52]. Patients with square-shaped teeth have
more favorable esthetic outcomes due to long proximal contacts and less papillary tissue,
whereas patients with triangular-shaped teeth have a proximal tooth contact located more
incisally and, thus, more tissue height to fill in and a high risk of gingival recession and
black triangle occurrence [53].
Likewise, overlooking the biotype of the gingiva when planning a fixed dental con-
struction could exacerbate the existing pathology [54,55]. For instance, the gingival crevice
depth and the gingival tissue thickness (biotype), as well as the alveolar crest location, vary
among patients and need consideration during the treatment [56,57]. It was found that
the gingival biotype plays an important role in the treatment result [6,21,58,59]. Having
knowledge of the characteristic features of gingival biotypes can help to minimize tissue
resorption and provide improved results in both tooth preparation and gum recession.
Biological width violation, as well as inappropriate tooth preparation, may lead to an
alteration in soft tissue thickness, transforming it into thin gingiva over time. It was con-
firmed that the thick gingiva may undergo alteration to a thin gingival biotype over time in
response to prosthetic treatment [41]. These thin, soft tissues have a higher predisposition
toward recession, which necessitates the supragingival placement of restoration margins
wherever possible.
León-Martínez et al. [60] studied the periodontal behavior of teeth prepared with
horizontal finishing crowns supporting fixed metal-ceramic, zirconia full-coverage crowns,
and fixed partial dentures. In the control teeth, they found higher plaque control and
bleeding upon probing, as well as probing pocket depth; whilst probing attachment levels
were higher around the teeth prepared with horizontal finishing lines supporting complete
coverage crowns and fixed partial dentures. Gingival migration was seen in periodontally
compromised teeth prepared with horizontal finishing lines. They concluded that the teeth
prepared with horizontal finishing lines supporting crowns and fixed partial dentures
present more periodontal disorders than untreated control teeth.
Another useful technique is the tooth preparation margin, a technique designed to
create an anatomic crown with a prosthetic emergence profile, which simulates the shape
of the natural tooth; it is also known as the biologically oriented preparation technique
(BOPT) [61,62]. This is a prosthetic technique for periodontally healthy teeth, which uses a
feather edge preparation in a flapless approach in both esthetic and posterior areas with
fixed prosthetic restorations, achieving high quality clinical and esthetic results in terms of
soft tissue stability at the prosthetic–tissue interface [63]. In addition, the BOPT technique
is simpler and faster during preparation impression taking, temporary crowns’ relining,
and creating the crowns’ profiles, up to the final prosthetic restoration when compared to
chamfer, shoulder, etc.
Agustín-Panadero et al. [61] studied the clinical behavior of crowns and fixed partial
dentures on teeth using a vertical preparation without finish line BOPT. They found that
two years after treatment, the vertical preparation without finish line BOPT produced
J. Funct. Biomater. 2022, 13, 15 7 of 21
gingival thickening, margin stability, and optimal esthetics. Neither crowns nor fixed
partial dentures showed any mechanical complications.
tal status of the mucosa under the pontic if the hygienic condition is not preserved via
plaque elimination. Therefore, the patients’ compliance regarding the preservation of good
hygienic conditions is essential for the survival of the dental construction [64,78].
Al-Sinaidi et al. [76] evaluated the periodontal health in subjects who received fixed
dental restorations, and the outcomes of subgingival and supragingival located crown
margins were also evaluated. The authors noticed higher gingival and plaque indexes as
well as a deeper periodontal pocket in the abutment teeth compared with non-abutment
teeth. Additionally, supporting teeth with higher gingival and plaque index scores as
well as probing pocket depth presented in patients who had their functioning fixed dental
restorations for approximately 5 years, as well as those who were older than 46-years old.
The teeth with subgingival positioned crown edges had considerably lower mean values
for their clinical parameters than the teeth with supragingival crown edges.
When dental prostheses demonstrate greater biofilm buildup and increased inflamma-
tory levels, this suggests that additional measures are required to control these factors [79].
These measures can be mechanical and chemical control aids. Mechanical control consists of
toothbrushes (manual or electric) and toothpaste as well as specific devices for interdental
cleaning. In addition, the chemical agents (antiseptics) exhibit antimicrobial benefits when
used for prosthesis disinfection, though only a few agents can be used safely without
causing damage. The most common chemical agents consist of three types of mouthwash
with antiplaque and antigingivitis effects, which are chlorhexidine (CHX); essential oils
(EOs), ranked second; and cetylpyridinium chloride (CPC) [80,81]. The CHX solution
(0.2%) is the most indicated [81]. EOs are the second choice as they are not as effective as
the CPC solution (0.05% to 0.75%), which, however, has a greater potential for adverse
reactions [80]. The adverse effects of mouthwash includes a transient loss of taste sensation,
bitter taste, soreness and burning sensation of the mucosa, dryness of the mucosa, and
epithelial desquamation [81]. Fluoride solutions can be used for high caries risk patients.
increases as the inflammation advances with the differential quantity of PMNs (95–97%),
mononucleocytes (2–3%), and lymphocytes (1–2%) [65,110].
Figure 4. Images of surface structure using scanning electron microscopy (at 200× magnification)
of ZLS (A1) and Y-TZP (A2); and confocal microscope images (20×) of fibroblasts on ZLS (B1) and
Y-TZP (B2) [100].
salivary pH in patients with chronic generalized gingivitis is more alkaline than that in
patients with clinically healthy gingiva. In patients with chronic generalized periodontitis,
the salivary pH is more acidic [111]. More studies are needed to study the physiology.
The qualitative and quantitative assessment of the GCF can be an indicator of the
periodontal status, and its examination helps in the diagnosis of oral diseases [117–120]. The
examination of the GCF can be a diagnostic tool to discover host-microbial communications
and to reveal the phase of periodontitis [121–123].
Heboyan et al. [42] studied the peculiar features of the GCF parameter dynamics
among subjects with fixed prosthetic constructions made using different biomaterials
and manufacturing techniques. The results of studying the amount of the excreted GCF
in subjects before the restoration of their masticatory function via dental prostheses of
various biomaterials and manufacturing techniques, as well as after prosthetic treatment,
found that the amount of excreted GCF increased 1.38-fold following restoration using
the conventionally fabricated cobalt-chromium-based ceramic prostheses. Furthermore,
the greatest amount of GCF is excreted in the first 6 months following the insertion of the
prosthesis. On the contrary, a decrease in the excretion of GCF volume is observed between
6 months and up to 1 year. An approximate 2-fold reduction in GCF volume was observed
in subjects with CAD/CAM fabricated restorations 12 months after prosthetic treatment.
The reduction in this value occurs progressively and approaches a value within the normal
range in the later period of up to 1 year. This tendency was noted in all prosthetic groups.
The results received upon studying the dynamics of the GCF volume before and after
the restoration of masticatory function found that the largest improvement in indexes is
noted among patients with zirconia-based dental prostheses, as well as with Co-Cr-based
ceramic prostheses fabricated by CAD/CAM technology. An insignificant GCF volume
increase seen a year after the insertion of a fixed metal–ceramic restoration among certain
subjects can be explained by poor oral hygiene, which influenced the statistical data of all
observation groups.
Furthermore, when the margins of the artificial crown are placed subgingivally, the
tissues of marginal gum are subjected to more noticeable inflammation. According to the
data, oral hygiene improves during the process of prosthetic treatment [21], with GCF
pH, and periodontal status changing [77,124] for the better. The study on the pH of GCF
found that following the restoration of masticatory function by dental prosthesis of various
frames and manufacturing techniques showed an increase in the pH index when compared
to the data obtained before the prosthetic treatment. The preventive measures lead to the
normalization of oral fluid pH due to the improvement of metabolic processes within the
oral cavity.
F. nucleatum are also capable to join and enter into the host epitheliocytes and initiate
the immune-inflammatory process of the host. Peptostreptococci are associated with other
microorganisms and considered pathogens of mixed infections.
Generally, most microbes of the oral microbiome are symbionts that sustain a high
degree of homeostasis and the healthy condition of the mouth [132]. The vast majority
of oral microbial species are saprophytes and not harmful to the host. Although various
microbes of biocenosis alter frequently in different regions of the human body, each person
typically has more or less specific bacterial populations. The challenges in the microbiologic
differentiating of Bacteroids in healthy and in different pathological situations of the oral
tissues do not permit the recognition of a definite causative agent of the pathological
process [124].
The differential microbial species and metabolites in the GCF among those with
periodontal pathology and healthy subjects are potential biological indicators, indicating
a possible approach to forecast, diagnose, and accomplish individualized periodontal
treatment [133–136]. Periodontal pathology is related to misbalanced homeostasis in the
oral tissues, microbial progression, and development of the dental biofilm on the dental
prostheses. However, data on periodontal pathogens relative to periodontitis and in subjects
with healthy periodontium are insufficiently presented. Moreover, the inter-relationship
between host and microorganisms, as well as biochemical metabolic processes, has not
been acknowledged [137,138].
The colonization of the gingival crevice with various microorganisms was observed
at various fixed prosthetic restorations. Candida albicans noted in smear samples re-
sulted in an inflammatory reaction in the periodontium when using Co-Cr-based ceramic
dental restorations of the conventional fabrication technique, which possibly related to
the weakening of the immunity in the gingival crevice. The same picture was revealed
when fixed Co-Cr-based ceramic restorations were made using the CAD/CAM technique;
there was a difference in the microflora number in the subjects who received the con-
ventionally fabricated Co-Cr-based ceramic dental restorations. Zirconia-based ceramic
restorations showed the best outcomes both in the qualitative and quantitative composition
of microbiota in the gingival crevice. After 12 months of prosthetic rehabilitation with
cobalt-chromium-based ceramic and zirconia-based ceramic fixed full coverage restora-
tions, a quantitative reduction in various microorganisms, such as Prevotella intermedia,
Streptococcus haemolyticus, Porphyromonas gingivalis, Fusobacterium spp., and Corynebacterium
anaerobium was observed [124].
It is worth mentioning that Candida albicans were found during the bacteriologic and
bacterioscopic analyses of subjects with fixed prosthetic restorations, within 1 year of
follow-up, which reliably confirmed their existence. Candida albicans is also presented
in normal microbiota in the form of saprophytes. Hence, the qualitative and quantitative
elements of fungal pathology can be exposed only via bacterioscopy. Recent research
showed the existence of pathological reactions in identifying more than six well-stained
pseudomycelia [124].
Mechanical preparation of the teeth is found to be harmful and to cause the worsening
of periodontal status if not done properly. Nevertheless, after 1 year of prosthetic rehabilita-
tion with fixed prosthetic constructions, periodontal recovery occurs among patients who
received constructions made using the CAD/CAM technique. Additionally, a quite notice-
able transformation towards clinical healing was revealed among patients with zirconia
restorations because zirconium is less harmful to the periodontal tissues due to the reduced
risk of dental biofilm accumulation. Additionally, zirconium is more biocompatible and tol-
erable to soft tissues and oral cavity structures [5,42]. Thus, the periodontium was healthier
in cases where the prosthetic treatment was accomplished using restorations manufactured
by the CAD/CAM technic. This could have been due to the biomaterial rather than the
manufacturing technique only [71,96]. Souza et al. [139] evaluated biofilm formation on
various biomaterials used in prosthetic rehabilitation. No significant differences (P < 0.05)
in absorbance and CFU/cm2 between biofilm growth on zirconia, porcelain, and titanium
J. Funct. Biomater. 2022, 13, 15 14 of 21
Figure 5. SEM figures received on commercially pure Ti surfaces (A,B) and Cr-Co-Mo alloys (C,D)
covered with biofilms after 24 h (A,C) and 48 h (B,D) of growth in a BHI medium supplemented with
5% sucrose. Figures obtained using secondary electrons mode (SE) at 10 kV [139].
J. Funct. Biomater. 2022, 13, 15 15 of 21
Figure 6. SEM figures received on feldspar-based ceramics (A,C) and Zr (B,D) covered with biofilms
after 24 h (A,B) and 48 h (C,D) of growth in a BHI medium supplemented with 5% sucrose. Figures
obtained using secondary electrons mode (SE) at 10 kV [139].
There has been considerable advancement in clinical dentistry [141–145]. With the use
of advanced 3D digital technologies, teeth preparation can be evaluated, and the prosthesis
can be fabricated accurately [146–148]. These help to minimize errors such as marginal gaps,
discrepancies, etc. At present, restorative dentists are refining their practice and dental
clinics are acclimatizing from conventional treatment methods to a digital workflow in the
fabrication of dental prostheses [149]. Indeed, 3D printing techniques are now employed in
developing simulators and models for dental education and the maintenance of prostheses.
However, expertise is needed for the digital additive manufacturing of dental restorations
used in prosthetic dentistry.
Finally, when planning a fixed dental prosthesis, adequate periodontal assessment
and treatment, appropriate instructions, and motivation in self-performed plaque control
as well as compliance to maintenance protocols, appear to be the most important factors
to limit or avoid any potential negative effects on the periodontium caused by fixed
prostheses [51,134].
9. Conclusions
Before starting prosthetic treatment, the condition of the periodontal tissues should be
evaluated for their oral hygiene status, as well as the gingival and periodontal conditions.
Determination of the gingival biotype, as well as the parameters of the GCF (amount, pH
index, microbiological and cytomorphometric parameters), helps in the assessment and
diagnosis of gingival and periodontal diseases as well as their successful management.
J. Funct. Biomater. 2022, 13, 15 16 of 21
Zirconium-based restorations made from the CAD/CAM technology provide better results,
in terms of marginal fit, inflammation reduction, maintenance, and the restoration of
periodontal health and oral hygiene, as compared to constructions made by conventional
method and from other alloys. Compared to subgingival margins, the supragingival
margins offer better oral hygiene, which can be maintained and does not lead to secondary
caries or periodontal disease.
Author Contributions: Conceptualization, A.H., Z.K., V.S. and D.R.; methodology, A.H. and D.R.;
software, A.H.; validation, D.R. and V.S.; formal analysis, A.H. and G.V.O.F.; investigation, A.H. and
D.R.; resources, A.H. and D.R.; data curation, A.H. and A.M.; writing—original draft preparation, A.H.
and D.R.; writing—review and editing, A.H., M.S.Z., Z.K., A.M., D.R. and G.V.O.F.; visualization, V.S.,
A.H., M.S.Z., Z.K., A.M. and D.R.; supervision, D.R. and V.S.; project administration, A.H.; funding
acquisition, V.S. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
References
1. Muddugangadhar, B.C.; Siddhi, T.; Suchismita, D. Prostho-perio-restorative interrelationship: A major junction. J. Adv. Oral Res.
2011, 2, 7–12. [CrossRef]
2. Mojon, P.; Rentsch, A.; Budtz-Jørgensen, E. Relationship between prosthodontic status, caries, and periodontal disease in a
geriatric population. Int. J. Prosthodont. 1995, 8, 564–571. [PubMed]
3. Hsu, Y.-T.; Huang, N.; Wang, H.-L.; Kuo, Y.-w.; Chen, M.; Liu, T.-K.; Lin, H.-N.; Kuo, S.-L.; Juan, P.-K.; Liao, P.-B. Relationship
between periodontics and prosthodontics: The two-way street. J. Prosthodont. Implantol. 2015, 4, 4–11.
4. Avetisyan, A.; Markaryan, M.; Rokaya, D.; Tovani-Palone, M.R.; Zafar, M.S.; Khurshid, Z.; Vardanyan, A.; Heboyan, A.
Characteristics of periodontal tissues in prosthetic treatment with fixed dental prostheses. Molecules 2021, 26, 1331. [CrossRef]
5. Hao, Y.; Huang, X.; Zhou, X.; Li, M.; Ren, B.; Peng, X.; Cheng, L. Influence of dental prosthesis and restorative materials interface
on oral biofilms. Int. J. Mol. Sci. 2018, 19, 3157. [CrossRef]
6. Yin, X.J.; Wei, B.Y.; Ke, X.P.; Zhang, T.; Jiang, M.Y.; Luo, X.Y.; Sun, H.Q. Correlation between clinical parameters of crown and
gingival morphology of anterior teeth and periodontal biotypes. BMC Oral Health 2020, 20, 59. [CrossRef]
7. Kossioni, A.E.; Dontas, A.S. The stomatognathic system in the elderly. Useful information for the medical practitioner. Clin. Interv.
Aging. 2007, 2, 591–597. [CrossRef]
8. Pihlstrom, B.L.; Michalowicz, B.S.; Johnson, N.W. Periodontal diseases. Lancet 2005, 366, 1809–1820. [CrossRef]
9. Nazir, M.A. Prevalence of periodontal disease, its association with systemic diseases and prevention. Int. J. Health Sci. 2017,
11, 72–80.
10. Kornman, K.S.; Van Dyke, T.E. Bringing light to the heat: “Inflammation and periodontal diseases: A reappraisal”. J. Periodontol.
2008, 79, 1313. [CrossRef]
11. Van Dyke, T.E.; Serhan, C.N. Resolution of inflammation: A new paradigm for the pathogenesis of periodontal diseases. J. Dent.
Res. 2003, 82, 82–90. [CrossRef] [PubMed]
12. Vita, J.A. Endothelial function. Circulation 2011, 124, e906–e912. [CrossRef] [PubMed]
13. Al-Odinee, N.M.; Al-Hamzi, M.; Al-Shami, I.Z.; Madfa, A.; Al-Kholani, A.I.; Al-Olofi, Y.M. Evaluation of the quality of fixed
prosthesis impressions in private laboratories in a sample from yemen. BMC Oral Health 2020, 20, 304. [CrossRef]
14. Knoernschild, K.L.; Campbell, S.D. Periodontal tissue responses after insertion of artificial crowns and fixed partial dentures.
J. Prosthet. Dent. 2000, 84, 492–498. [CrossRef] [PubMed]
15. Heboyan, A. Marginal and internal fit of fixed prosthodontic constructions: A literature review. Int. J. Dent. Res. Rev. 2019, 2, 19.
[CrossRef]
16. Karataşli, O.; Kursoğlu, P.; Capa, N.; Kazazoğlu, E. Comparison of the marginal fit of different coping materials and designs
produced by computer aided manufacturing systems. Dent. Mater. J. 2011, 30, 97–102. [CrossRef]
17. Tan, P.L.; Gratton, D.G.; Diaz-Arnold, A.M.; Holmes, D.C. An in vitro comparison of vertical marginal gaps of cad/cam titanium
and conventional cast restorations. J. Prosthodont. 2008, 17, 378–383. [CrossRef]
18. Siadat, H.; Alikhasi, M.; Mirfazaelian, A.; Zade, M.M. Scanning electron microscope evaluation of vertical and horizontal
discrepancy in cast copings for single-tooth implant-supported prostheses. Implant Dent. 2008, 17, 299–308. [CrossRef]
19. Reich, S.; Gozdowski, S.; Trentzsch, L.; Frankenberger, R.; Lohbauer, U. Marginal fit of heat-pressed vs. Cad/cam processed
all-ceramic onlays using a milling unit prototype. Oper. Dent. 2008, 33, 644–650. [CrossRef]
J. Funct. Biomater. 2022, 13, 15 17 of 21
20. Ushiwata, O.; de Moraes, J.V. Method for marginal measurements of restorations: Accessory device for toolmakers microscope. J.
Prosthet. Dent. 2000, 83, 362–366. [CrossRef]
21. Spagnuolo, G.; Desiderio, C.; Rivieccio, V.; Amato, M.; Rossetti, D.V.; D’Antò, V.; Schweikl, H.; Lupi, A.; Rengo, S.; Nocca, G.
In vitro cellular detoxification of triethylene glycol dimethacrylate by adduct formation with N-acetylcysteine. Dent Mater. 2013,
29, e153-60. [CrossRef] [PubMed]
22. Keshvad, A.; Hooshmand, T.; Asefzadeh, F.; Khalilinejad, F.; Alihemmati, M.; Van Noort, R. Marginal gap, internal fit, and fracture
load of leucite-reinforced ceramic inlays fabricated by cerec inlab and hot-pressed techniques. J. Prosthodont. 2011, 20, 535–540.
[CrossRef] [PubMed]
23. Guess, P.C.; Vagkopoulou, T.; Zhang, Y.; Wolkewitz, M.; Strub, J.R. Marginal and internal fit of heat pressed versus cad/cam
fabricated all-ceramic onlays after exposure to thermo-mechanical fatigue. J. Dent. 2014, 42, 199–209. [CrossRef] [PubMed]
24. Riccitiello, F.; Amato, M.; Leone, R.; Spagnuolo, G.; Sorrentino, R. In vitro evaluation of the marginal fit and internal adaptation
of zirconia and lithium disilicate single crowns: Micro-ct comparison between different manufacturing procedures. Open Dent. J.
2018, 12, 160–172. [CrossRef]
25. Neves, F.D.; Prado, C.J.; Prudente, M.S.; Carneiro, T.A.; Zancopé, K.; Davi, L.R.; Mendonça, G.; Cooper, L.F.; Soares, C.J. Micro-
computed tomography evaluation of marginal fit of lithium disilicate crowns fabricated by using chairside cad/cam systems or
the heat-pressing technique. J. Prosthet. Dent. 2014, 112, 1134–1140. [CrossRef]
26. Mously, H.A.; Finkelman, M.; Zandparsa, R.; Hirayama, H. Marginal and internal adaptation of ceramic crown restorations
fabricated with cad/cam technology and the heat-press technique. J. Prosthet. Dent. 2014, 112, 249–256. [CrossRef]
27. Freire, Y.; Gonzalo, E.; Lopez-Suarez, C.; Suarez, M.J. The marginal fit of cad/cam monolithic ceramic and metal-ceramic crowns.
J. Prosthodont. 2019, 28, 299–304. [CrossRef]
28. Ahrberg, D.; Lauer, H.C.; Ahrberg, M.; Weigl, P. Evaluation of fit and efficiency of cad/cam fabricated all-ceramic restorations
based on direct and indirect digitalization: A double-blinded, randomized clinical trial. Clin. Oral Investig. 2016, 20, 291–300.
[CrossRef]
29. Abdullah, A.O.; Tsitrou, E.A.; Pollington, S. Comparative in vitro evaluation of cad/cam vs. conventional provisional crowns. J.
Appl. Oral Sci. 2016, 24, 258–263. [CrossRef]
30. Heboyan, A.G.; Movsisyan, N.M.; Khachatryan, V.A. Provisional restorations in restorative dentistry. World Sci. 2019, 3, 11–17.
31. Sorrentino, R.; Navarra, C.O.; Di Lenarda, R.; Breschi, L.; Zarone, F.; Cadenaro, M.; Spagnuolo, G. Effects of finish line design and
fatigue cyclic loading on phase transformation of zirconia dental ceramics: A qualitative micro-raman spectroscopic analysis.
Materials 2019, 12, 863. [CrossRef] [PubMed]
32. Heboyan, A.; Vardanyan, A.; Avetisyan, A. Cement selection in dental practice. World Sci. 2019, 2, 4–9.
33. Diaz, P.I.; Chalmers, N.I.; Rickard, A.H.; Kong, C.; Milburn, C.L.; Palmer, R.J., Jr.; Kolenbrander, P.E. Molecular characterization of
subject-specific oral microflora during initial colonization of enamel. Appl. Environ. Microbiol. 2006, 72, 2837–2848. [CrossRef]
[PubMed]
34. Pihlstrom, B.L. Periodontal risk assessment, diagnosis and treatment planning. Periodontol. 2000 2001, 25, 37–58. [CrossRef]
[PubMed]
35. Kazmi, S.M.R.; Iqbal, Z.; Muneer, M.U.; Riaz, S.; Zafar, M.S. Different pontic design for porcelain fused to metal fixed dental
prosthesis: Contemporary guidelines and practice by general dental practitioners. Eur. J. Dent. 2018, 12, 375–379. [CrossRef]
[PubMed]
36. Rashid, H. How does fixed prosthodontics interface with periodontology? J. Res. Dent. 2015, 3, 96. [CrossRef]
37. Goldberg, P.V.; Higginbottom, F.L.; Wilson, T.G. Periodontal considerations in restorative and implant therapy. Periodontol. 2000
2001, 25, 100–109. [CrossRef]
38. Memari, Y.; Mohajerfar, M.; Armin, A.; Kamalian, F.; Rezayani, V.; Beyabanaki, E. Marginal adaptation of cad/cam all-ceramic
crowns made by different impression methods: A literature review. J. Prosthodont. 2019, 28, e536–e544. [CrossRef]
39. Tao, J.; Wu, Y.; Chen, J.; Su, J. A follow-up study of up to 5 years of metal-ceramic crowns in maxillary central incisors for different
gingival biotypes. Int. J. Periodontics Restor. Dent. 2014, 34, e85–e92. [CrossRef]
40. Yin, J.; Liu, D.; Huang, Y.; Wu, L.; Tang, X. Cad/cam techniques help in the rebuilding of ideal marginal gingiva contours of
anterior maxillary teeth: A case report. J. Am. Dent. Assoc. 2017, 148, 834–839.e838. [CrossRef]
41. Popa, D.; Bordea, I.R.; Burde, A.V.; Crisan, B.; Campian, R.S.; Constantiniuc, M. Surface modification of zirconia after laser
irradiation. Optoelectron. Adv. Mater. Rapid Commun. 2016, 10, 785–788.
42. Heboyan, A.; Manrikyan, M.; Markaryan, M.; Vardanyan, I. Changes in the parameters of gingival crevicular fluid in masticatory
function restoration by various prosthodontic constructions. Int. J. Pharm. Sci. Res. 2020, 12, 2088–2093.
43. Kois, J.C. The restorative-periodontal interface: Biological parameters. Periodontol. 2000 1996, 11, 29–38. [CrossRef] [PubMed]
44. Makigusa, K. Histologic comparison of biologic width around teeth versus implant: The effect on bone preservation. J. Implant.
Reconstr. Dent. 2009, 1, 20–24.
45. Nugala, B.; Kumar, B.S.; Sahitya, S.; Krishna, P.M. Biologic width and its importance in periodontal and restorative dentistry. J.
Conserv. Dent. 2012, 15, 12–17. [CrossRef]
46. Gargiulo, A.W.; Wentz, F.M.; Orban, B. Dimensions and relations of the dentogingival junction in humans. J. Periodontol. 1961,
32, 261–267. [CrossRef]
J. Funct. Biomater. 2022, 13, 15 18 of 21
47. Kina, J.R.; Dos Santos, P.H.; Kina, E.F.; Suzuki, T.Y.; Dos Santos, P.L. Periodontal and prosthetic biologic considerations to restore
biological width in posterior teeth. J. Craniofac. Surg. 2011, 22, 1913–1916. [CrossRef]
48. Doornewaard, R.; Bruyn, H.; Matthys, C.; Bronkhorst, E.; Vandeweghe, S.; Vervaeke, S. The long-term effect of adapting the
vertical position of implants on peri-implant health: A 5-year intra-subject comparison in the edentulous mandible including oral
health-related quality of life. J. Clin. Med. 2020, 9, 3320. [CrossRef]
49. Nevins, M.; Skurow, H.M. The intracrevicular restorative margin, the biologic width, and the maintenance of the gingival margin.
Int. J. Periodontics Restor. Dent. 1984, 4, 30–49.
50. Reitemeier, B.; Hänsel, K.; Walter, M.H.; Kastner, C.; Toutenburg, H. Effect of posterior crown margin placement on gingival
health. J. Prosthet. Dent. 2002, 87, 167–172. [CrossRef]
51. Ercoli, C.; Caton, J.G. Dental prostheses and tooth-related factors. J. Periodontol. 2018, 89, S223–S236. [CrossRef] [PubMed]
52. Olsson, M.; Lindhe, J. Periodontal characteristics in individuals with varying form of the upper central incisors. J. Clin. Periodontol.
1991, 18, 78–82. [CrossRef] [PubMed]
53. Dhir, S. The peri-implant esthetics: An unforgettable entity. J. Indian Soc. Periodontol. 2011, 15, 98–103. [CrossRef] [PubMed]
54. Kolte, R.; Kolte, A.; Mahajan, A. Assessment of gingival thickness with regards to age, gender and arch location. J. Indian Soc.
Periodontol. 2014, 18, 478–481. [CrossRef]
55. Zweers, J.; Thomas, R.Z.; Slot, D.E.; Weisgold, A.S.; Van der Weijden, F.G. Characteristics of periodontal biotype, its dimensions,
associations and prevalence: A systematic review. J. Clin. Periodontol. 2014, 41, 958–971. [CrossRef]
56. Nagaraj, K.R.; Savadi, R.C.; Savadi, A.R.; Prashanth Reddy, G.T.; Srilakshmi, J.; Dayalan, M.; John, J. Gingival biotype—
Prosthodontic perspective. J. Indian Prosthodont. Soc. 2010, 10, 27–30. [CrossRef]
57. Kan, J.Y.; Rungcharassaeng, K.; Morimoto, T.; Lozada, J. Facial gingival tissue stability after connective tissue graft with single
immediate tooth replacement in the esthetic zone: Consecutive case report. J. Oral Maxillofac. Surg. 2009, 67, 40–48. [CrossRef]
58. Shah, N.; Goyal, S. A study of neurocognitive and executive function of divers. J. Interdiscip. Dent. 2016, 6, 44–49. [CrossRef]
59. Shah, D.; Duseja, S.; Vaishnav, K.; Shah, R. Adaptation of gingival biotype in response to prosthetic rehabilitation. Adv. Hum. Biol.
2017, 7, 85–88. [CrossRef]
60. León-Martínez, R.; Montiel-Company, J.M.; Bellot-Arcís, C.; Solá-Ruíz, M.F.; Selva-Otaolaurruchi, E.; Agustín-Panadero, R.
Periodontal behavior around teeth prepared with finishing line for restoration with fixed prostheses. A systematic review and
meta-analysis. J. Clin. Med. 2020, 9, 249. [CrossRef]
61. Agustín-Panadero, R.; Serra-Pastor, B.; Fons-Font, A.; Solá-Ruíz, M.F. Prospective clinical study of zirconia full-coverage
restorations on teeth prepared with biologically oriented preparation technique on gingival health: Results after two-year
follow-up. Oper. Dent. 2018, 43, 482–487. [CrossRef] [PubMed]
62. Agustín-Panadero, R.; Solá-Ruíz, M.F. Vertical preparation for fixed prosthesis rehabilitation in the anterior sector. J. Prosthet.
Dent. 2015, 114, 474–478. [CrossRef]
63. Loi, I.; Di Felice, A. Biologically oriented preparation technique (bopt): A new approach for prosthetic restoration of periodontically
healthy teeth. Eur. J. Esthet. Dent. Off. J. Eur. Acad. Esthet. Dent. 2013, 8, 10–23.
64. Abduo, J.; Lyons, K.M. Interdisciplinary interface between fixed prosthodontics and periodontics. Periodontol. 2000 2017, 74, 40–62.
[CrossRef] [PubMed]
65. Cekici, A.; Kantarci, A.; Hasturk, H.; Van Dyke, T.E. Inflammatory and immune pathways in the pathogenesis of periodontal
disease. Periodontol. 2000 2014, 64, 57–80. [CrossRef]
66. Ercoli, C.; Caton, J.G. Dental prostheses and tooth-related factors. J. Clin. Periodontol. 2018, 45 (Suppl. S20), S207–S218. [CrossRef]
67. Garlet, G.P. Destructive and protective roles of cytokines in periodontitis: A re-appraisal from host defense and tissue destruction
viewpoints. J. Dent. Res. 2010, 89, 1349–1363. [CrossRef]
68. Nakamura, K.; Kanno, T.; Milleding, P.; Ortengren, U. Zirconia as a dental implant abutment material: A systematic review. Int. J.
Prosthodont. 2010, 23, 299–309.
69. Zarone, F.; Di Mauro, M.I.; Spagnuolo, G.; Gherlone, E.; Sorrentino, R. Fourteen-year evaluation of posterior zirconia-based
three-unit fixed dental prostheses: A prospective clinical study of all ceramic prosthesis. J. Dent. 2020, 101, 103419. [CrossRef]
70. Xu, X.Y.; Zhang, Y.L.; Geng, F.H. Clinical efficacy and effects of cad/cam zirconia all-ceramic crown and metal-ceramic crown
restoration on periodontal tissues. Shanghai Kou Qiang Yi Xue Shanghai J. Stomatol. 2017, 26, 331–335.
71. Pabst, A.M.; Walter, C.; Grassmann, L.; Weyhrauch, M.; Brüllmann, D.D.; Ziebart, T.; Scheller, H.; Lehmann, K.M. Influence of
cad/cam all-ceramic materials on cell viability, migration ability and adenylate kinase release of human gingival fibroblasts and
oral keratinocytes. Clin. Oral Investig. 2014, 18, 1111–1118. [CrossRef] [PubMed]
72. Wataha, J.C. Biocompatibility of dental casting alloys: A review. J. Prosthet. Dent. 2000, 83, 223–234. [CrossRef]
73. Kc Basnyat, S.; Sapkota, B.; Shrestha, S. Oral hygiene and gingival health in patients with fixed prosthodontic appliances—A six
month follow-up. Kathmandu Univ. Med. J. (KUMJ) 2015, 13, 328–332.
74. McClanahan, S.F.; Bartizek, R.D.; Biesbrock, A.R. Identification and consequences of distinct löe-silness gingival index examiner
styles for the clinical assessment of gingivitis. J. Periodontol. 2001, 72, 383–392. [CrossRef] [PubMed]
75. Bluma, E.; Vidzis, A.; Zigurs, G. The influence of fixed prostheses on periodontal health. Stomatologija 2016, 18, 112–121.
76. Al-Sinaidi, A.; Preethanath, R.S. The effect of fixed partial dentures on periodontal status of abutment teeth. Saudi J. Dent. Res.
2014, 5, 104–108. [CrossRef]
J. Funct. Biomater. 2022, 13, 15 19 of 21
77. Heboyan, A.; Syed, A.U.Y.; Rokaya, D.; Cooper, P.R.; Manrikyan, M.; Markaryan, M. Cytomorphometric analysis of inflammation
dynamics in the periodontium following the use of fixed dental prostheses. Molecules 2020, 25, 4650. [CrossRef]
78. Rokaya, D.; Mahat, Y.; Sapkota, B.; Kc Basnyat, S. Full coverage crowns and resin-bonded bridge combination for missing
mandibular anterior teeth. Kathmandu Univ. Med. J. (KUMJ) 2018, 16, 97–99.
79. Cortelli, S.C.; Costa, F.O.; Rode, S.M.; Haas, A.N.; Andrade, A.K.P.; Pannuti, C.M.; Escobar, E.C.; Almeida, E.R.; Cortelli, J.R.;
Pedrazzi, V. Mouthrinse recommendation for prosthodontic patients. Braz. Oral Res. 2014, 28, 1–9. [CrossRef]
80. Gunsolley, J.C. Clinical efficacy of antimicrobial mouthrinses. J. Dent. 2010, 38 (Suppl. S1), S6–S10. [CrossRef]
81. Vyas, T.; Bhatt, G.; Gaur, A.; Sharma, C.; Sharma, A.; Nagi, R. Chemical plaque control—A brief review. J. Family Med. Prim. Care.
2021, 10, 1562–1568. [CrossRef] [PubMed]
82. Cecilia, E.C.; Myriam, A.K.; María, E.L. Cytological analysis of the periodontal pocket in patients with aggressive periodontitis
and chronic periodontitis. Contemp. Clin. Dent. 2014, 5, 495–500. [CrossRef] [PubMed]
83. Armitage, G.C. Analysis of gingival crevice fluid and risk of progression of periodontitis. Periodontol. 2000 2004, 34, 109–119.
[CrossRef] [PubMed]
84. Shin, H.; Zhang, Y.; Jagannathan, M.; Hasturk, H.; Kantarci, A.; Liu, H.; Van Dyke, T.E.; Ganley-Leal, L.M.; Nikolajczyk, B.S. B
cells from periodontal disease patients express surface toll-like receptor 4. J. Leukoc. Biol. 2009, 85, 648–655. [CrossRef]
85. Sigusch, B.; Eick, S.; Pfister, W.; Klinger, G.; Glockmann, E. Altered chemotactic behavior of crevicular pmns in different forms of
periodontitis. J. Clin. Periodontol. 2001, 28, 162–167. [CrossRef]
86. Hou, G.-L.; Hou, L.-T.; Weisgold, A. Survival rate of teeth with periodontally hopeless prognosis after therapies with intentional
replantation and perioprosthetic procedures—A study of case series for 5–12 years. Clin. Exp. Dent. 2016, 2, 85–95. [CrossRef]
87. Moimaz, S.; Saliba, N.; Saliba, O.; Zina, L.; Bolonhez, M. Association between dental prosthesis and periodontal disease in a rural
brazilian community. Braz. J. Oral Sci. 2016, 5, 1226–1231.
88. Geurtsen, W. Biocompatibility of dental casting alloys. Crit. Rev. Oral Biol. Med. 2002, 13, 71–84. [CrossRef]
89. Elshahawy, W.; Watanabe, I. Biocompatibility of dental alloys used in dental fixed prosthodontics. Tanta Dent. J. 2014, 11, 150–159.
[CrossRef]
90. Eliaz, N. Corrosion of metallic biomaterials: A review. Materials 2019, 12, 407. [CrossRef]
91. Srimaneepong, V.; Rokaya, D.; Thunyakitpisal, P.; Qin, J.; Saengkiettiyut, K. Corrosion resistance of graphene oxide/silver
coatings on ni-ti alloy and expression of il-6 and il-8 in human oral fibroblasts. Sci. Rep. 2020, 10, 3247. [CrossRef]
92. Rokaya, D.; Srimaneepong, V.; Qin, J.; Thunyakitpisal, P.; Siraleartmukul, K. Surface adhesion properties and cytotoxicity of
graphene oxide coatings and graphene oxide/silver nanocomposite coatings on biomedical niti alloy. Sci. Adv. Mater. 2019,
11, 1474–1487. [CrossRef]
93. Rokaya, D.; Srimaneepong, V.; Qin, J.; Siraleartmukul, K.; Siriwongrungson, V. Graphene oxide/silver nanoparticle coating pro-
duced by electrophoretic deposition improved the mechanical and tribological properties of niti alloy for biomedical applications.
J. Nanosci. Nanotechnol. 2019, 19, 3804–3810. [CrossRef]
94. Gautam, C.; Joyner, J.; Gautam, A.; Rao, J.; Vajtai, R. Zirconia based dental ceramics: Structure, mechanical properties, biocompati-
bility and applications. Dalton Trans. 2016, 45, 19194–19215. [CrossRef]
95. Mallineni, S.K.; Nuvvula, S.; Matinlinna, J.P.; Yiu, C.K.; King, N.M. Biocompatibility of various dental materials in contemporary
dentistry: A narrative insight. J. Investig. Clin. Dent. 2013, 4, 9–19. [CrossRef]
96. Shang, L.J.; Wu, Y.; Xu, Y.J. Effect of the cad/cam zirconia all-ceramic crown restoration on periodontal tissue. Chin. J. Tissue Eng.
Res. 2014, 18, 4804–4809.
97. Gupta, G. Gingival crevicular fluid as a periodontal diagnostic indicator- ii: Inflammatory mediators, host-response modifiers
and chair side diagnostic aids. J. Med. Life 2013, 6, 7–13.
98. Hasiuk, P.; Hasiuk, N.; Kindiy, D.; Ivanchyshyn, V.; Kalashnikov, D.; Zubchenko, S. Characteristics of cellular composition of
periodontal pockets. Interv. Med. Appl. Sci. 2016, 8, 172–177. [CrossRef]
99. Kantarci, A.; Oyaizu, K.; Van Dyke, T.E. Neutrophil-mediated tissue injury in periodontal disease pathogenesis: Findings from
localized aggressive periodontitis. J. Periodontol. 2003, 74, 66–75. [CrossRef]
100. Rizo-Gorrita, M.; Luna-Oliva, I.; Serrera-Figallo, M.-Á.; Gutiérrez-Pérez, J.-L.; Torres-Lagares, D. Comparison of cytomorphometry
and early cell response of human gingival fibroblast (hgfs) between zirconium and new zirconia-reinforced lithium silicate
ceramics (zls). Int. J. Mol. Sci. 2018, 19, 2718. [CrossRef]
101. Bretz, W.A.; Weyant, R.J.; Corby, P.M.; Ren, D.; Weissfeld, L.; Kritchevsky, S.B.; Harris, T.; Kurella, M.; Satterfield, S.;
Visser, M.; et al. Systemic inflammatory markers, periodontal diseases, and periodontal infections in an elderly population. J. Am.
Geriatr. Soc. 2005, 53, 1532–1537. [CrossRef]
102. Nair, S.; Faizuddin, M.; Dharmapalan, J. Role of autoimmune responses in periodontal disease. Autoimmune. Dis. 2014,
2014, 596824. [CrossRef]
103. Van Dyke, T.E.; Kornman, K.S. Inflammation and factors that may regulate inflammatory response. J. Periodontol. 2008,
79, 1503–1507. [CrossRef]
104. Andrews, T.; Sullivan, K.E. Infections in patients with inherited defects in phagocytic function. Clin. Microbiol. Rev. 2003,
16, 597–621. [CrossRef]
105. Bosshardt, D.D.; Lang, N.P. The junctional epithelium: From health to disease. J. Dent. Res. 2005, 84, 9–20. [CrossRef]
J. Funct. Biomater. 2022, 13, 15 20 of 21
106. Delima, A.J.; Van Dyke, T.E. Origin and function of the cellular components in gingival crevice fluid. Periodontol. 2000 2003,
31, 55–76. [CrossRef]
107. Bykov, V.L. Human gingival immunocompetent cells in the norm and in inflammatory periodontal diseases. Arkh. Patol. 2005,
67, 51–55.
108. Biselli, R.; Ferlini, C.; Di Murro, C.; Paolantonio, M.; Fattorossi, A. Flow cytometric approach to human polymorphonuclear
leukocyte activation induced by gingival crevicular fluid in periodontal disease. Inflammation 1995, 19, 479–487. [CrossRef]
109. Gupta, G. Gingival crevicular fluid as a periodontal diagnostic indicator–i: Host derived enzymes and tissue breakdown products.
J. Med. Life 2012, 5, 390–397.
110. Ebersole, J.L. Humoral immune responses in gingival crevice fluid: Local and systemic implications. Periodontol. 2000 2003,
31, 135–166. [CrossRef]
111. Baliga, S.; Muglikar, S.; Kale, R. Salivary ph: A diagnostic biomarker. J. Indian Soc. Periodontol. 2013, 17, 461–465. [CrossRef]
112. Lynge Pedersen, A.M.; Belstrøm, D. The role of natural salivary defences in maintaining a healthy oral microbiota. J. Dent. 2019,
80, S3–S12. [CrossRef]
113. Bickel, M.; Munoz, J.L.; Giovannini, P. Acid-base properties of human gingival crevicular fluid. J. Dent. Res. 1985, 64, 1218–1220.
[CrossRef]
114. Galgut, P.N. The relevance of ph to gingivitis and periodontitis. J. Int. Acad. Periodontol. 2001, 3, 61–67.
115. Takahashi, N.; Saito, K.; Schachtele, C.F.; Yamada, T. Acid tolerance and acid-neutralizing activity of porphyromonas gingivalis,
prevotella intermedia and fusobacterium nucleatum. Oral Microbiol. Immunol. 1997, 12, 323–328. [CrossRef]
116. Takahashi, N.; Schachtele, C.F. Effect of ph on the growth and proteolytic activity of porphyromonas gingivalis and bacteroides
intermedius. J. Dent. Res. 1990, 69, 1266–1269. [CrossRef]
117. Smith, Q.T.; Au, G.S.; Freese, P.L.; Osborn, J.B.; Stoltenberg, J.L. Five parameters of gingival crevicular fluid from eight surfaces in
periodontal health and disease. J. Periodontal. Res. 1992, 27, 466–475. [CrossRef]
118. Khurshid, Z.; Mali, M.; Naseem, M.; Najeeb, S.; Zafar, M.S. Human gingival crevicular fluids (gcf) proteomics: An overview.
Dent. J. 2017, 5, 12. [CrossRef]
119. Fatima, T.; Khurshid, Z.; Rehman, A.; Imran, E.; Srivastava, K.C.; Shrivastava, D. Gingival crevicular fluid (gcf): A diagnostic tool
for the detection of periodontal health and diseases. Molecules 2021, 26, 1208.
120. Khurshid, Z.; Warsi, I.; Moin, S.F.; Slowey, P.D.; Latif, M.; Zohaib, S.; Zafar, M.S. Biochemical analysis of oral fluids for disease
detection. Adv. Clin. Chem. 2021, 100, 205–253.
121. Costantini, E.; Sinjari, B.; Piscopo, F.; Porreca, A.; Reale, M.; Caputi, S.; Murmura, G. Evaluation of salivary cytokines and vitamin
d levels in periodontopathic patients. Int. J. Mol. Sci. 2020, 21, 2669. [CrossRef]
122. Embery, G.; Waddington, R. Gingival crevicular fluid: Biomarkers of periodontal tissue activity. Adv. Dent. Res. 1994, 8, 329–336.
[CrossRef]
123. Ercoli, C.; Tarnow, D.; Poggio, C.E.; Tsigarida, A.; Ferrari, M.; Caton, J.G.; Chochlidakis, K. The relationships between tooth-
supported fixed dental prostheses and restorations and the periodontium. J. Prosthodont. 2021, 30, 305–317. [CrossRef]
124. Heboyan, A.; Manrikyan, M.; Zafar, M.S.; Rokaya, D.; Nushikyan, R.; Vardanyan, I.; Vardanyan, A.; Khurshid, Z. Bacteriological
evaluation of gingival crevicular fluid in teeth restored using fixed dental prostheses: An in vivo study. Int. J. Mol. Sci. 2021,
22, 5463. [CrossRef]
125. Said, H.S.; Suda, W.; Nakagome, S.; Chinen, H.; Oshima, K.; Kim, S.; Kimura, R.; Iraha, A.; Ishida, H.; Fujita, J.; et al. Dysbiosis
of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers. DNA Res. 2014,
21, 15–25. [CrossRef]
126. Xie, H.; Cook, G.S.; Costerton, J.W.; Bruce, G.; Rose, T.M.; Lamont, R.J. Intergeneric communication in dental plaque biofilms. J.
Bacteriol. 2000, 182, 7067–7069. [CrossRef]
127. Periasamy, S.; Kolenbrander, P.E. Mutualistic biofilm communities develop with porphyromonas gingivalis and initial, early, and
late colonizers of enamel. J. Bacteriol. 2009, 191, 6804–6811. [CrossRef]
128. Elmanfi, S.; Zhou, J.; Sintim, H.O.; Könönen, E.; Gürsoy, M.; Gürsoy, U.K. Regulation of gingival epithelial cytokine response by
bacterial cyclic dinucleotides. J. Oral Microbiol. 2019, 11, 1538927. [CrossRef]
129. Holt, S.C.; Kesavalu, L.; Walker, S.; Genco, C.A. Virulence factors of porphyromonas gingivalis. Periodontol. 2000 1999, 20, 168–238.
[CrossRef]
130. Benakanakere, M.; Kinane, D.F. Innate cellular responses to the periodontal biofilm. Front. Oral Biol. 2012, 15, 41–55.
131. Holt, S.C.; Ebersole, J.L. Porphyromonas gingivalis, treponema denticola, and tannerella forsythia: The “red complex”, a prototype
polybacterial pathogenic consortium in periodontitis. Periodontol. 2000 2005, 38, 72–122. [CrossRef] [PubMed]
132. Willis, J.R.; Gabaldón, T. The human oral microbiome in health and disease: From sequences to ecosystems. Microorganisms 2020,
8, 308. [CrossRef] [PubMed]
133. Pei, J.; Li, F.; Xie, Y.; Liu, J.; Yu, T.; Feng, X. Microbial and metabolomic analysis of gingival crevicular fluid in general chronic
periodontitis patients: Lessons for a predictive, preventive, and personalized medical approach. EPMA J. 2020, 11, 197–215.
[CrossRef]
134. Patini, R.; Gallenzi, P.; Spagnuolo, G.; Cordaro, M.; Cantiani, M.; Amalfitano, A.; Arcovito, A.; Callà, C.; Mingrone, G.; Nocca, G.
Correlation between metabolic syndrome, periodontitis and reactive oxygen species production. A pilot study. Open Dent. J. 2017,
11, 621–627. [CrossRef] [PubMed]
J. Funct. Biomater. 2022, 13, 15 21 of 21
135. Cafiero, C.; Spagnuolo, G.; Marenzi, G.; Martuscelli, R.; Colamaio, M.; Leuci, S. Predictive periodontitis: The most promising
salivary biomarkers for early diagnosis of periodontitis. J. Clin. Med. 2021, 10, 1488. [CrossRef]
136. Del Giudice, C.; Vaia, E.; Liccardo, D.; Marzano, F.; Valletta, A.; Spagnuolo, G.; Ferrara, N.; Rengo, C.; Cannavo, A.; Rengo, G.
Infective endocarditis: A focus on oral microbiota. Microorganisms 2021, 9, 1218. [CrossRef]
137. Könönen, E.; Gursoy, M.; Gursoy, U.K. Periodontitis: A multifaceted disease of tooth-supporting tissues. J. Clin. Med. 2019,
8, 1135. [CrossRef]
138. Socransky, S.S.; Haffajee, A.D.; Cugini, M.A.; Smith, C.; Kent, R.L., Jr. Microbial complexes in subgingival plaque. J. Clin.
Periodontol. 1998, 25, 134–144. [CrossRef]
139. Souza, J.C.; Mota, R.R.; Sordi, M.B.; Passoni, B.B.; Benfatti, C.A.; Magini, R.S. Biofilm formation on different materials used in oral
rehabilitation. Braz. Dent. J. 2016, 27, 141–147. [CrossRef]
140. Sinjari, B.; Murmura, G.; Caputi, S.; Ricci, L.; Varvara, G.; Scarano, A. Use of oral chroma™ in the assessment of volatile sulfur
compounds in patients with fixed protheses. Int. J. Immunopathol. Pharmacol. 2013, 26, 691–697. [CrossRef]
141. Alauddin, M.S.; Baharuddin, A.S.; Mohd Ghazali, M.I. The modern and digital transformation of oral health care: A mini review.
Healthcare 2021, 9, 118. [CrossRef] [PubMed]
142. Humagain, M.; Rokaya, D. Integrating digital technologies in dentistry to enhance the clinical success. Kathmandu Univ. Med. J.
(KUMJ) 2019, 17, 256–257.
143. Schwendicke, F. Digital dentistry: Advances and challenges. J. Clin. Med. 2020, 9, 4005. [CrossRef] [PubMed]
144. Amornvit, P.; Rokaya, D.; Peampring, C.; Sanohkan, S. Confocal 3d optical intraoral scanners and comparison of image capturing
accuracy. Comput. Mater. Contin. 2021, 66, 303–314. [CrossRef]
145. Amornvit, P.; Rokaya, D.; Sanohkan, S. Comparison of accuracy of current ten intraoral scanners. BioMed Res. Int. 2021,
2021, 2673040. [CrossRef]
146. Tian, Y.; Chen, C.; Xu, X.; Wang, J.; Hou, X.; Li, K.; Lu, X.; Shi, H.; Lee, E.-S.; Jiang, H.B. A review of 3d printing in dentistry:
Technologies, affecting factors, and applications. Scanning 2021, 2021, 9950131. [CrossRef]
147. Dawood, A.; Marti Marti, B.; Sauret-Jackson, V.; Darwood, A. 3d printing in dentistry. Br. Dent. J. 2015, 219, 521–529. [CrossRef]
148. Schweiger, J.; Edelhoff, D.; Güth, J.F. 3d printing in digital prosthetic dentistry: An overview of recent developments in additive
manufacturing. J. Clin. Med. 2021, 10, 2010. [CrossRef]
149. Pillai, S.; Upadhyay, A.; Khayambashi, P.; Farooq, I.; Sabri, H.; Tarar, M.; Lee, K.T.; Harb, I.; Zhou, S.; Wang, Y.; et al. Dental
3d-printing: Transferring art from the laboratories to the clinics. Polymers 2021, 13, 157. [CrossRef]