Republic of Iraq Ministry of

Higher Education and

Scientific Research
Mustansiriyah University
College of dentistry

Strategies for periodontal disease

prevention and treatment: comprehensive
guide

A seminar Submitted to The College of Dentistry, Mustansiriyah University

Department of pedodontics orthodontic and preventive dentistry in Partial
Fulfillment for the Master Degree in preventive dentistry

By
Sara Yashar Faiiq

Supervised by:
Dr. Dunia Ahmed

1445Hijri 2025 D.C

1
 Supervisor Certification

I certify that this seminar was prepared by the Master student (Sara
Yashar Faiiq Abd AL-Hadi) under my/our supervision at College of
Dentistry, Mustansiriyah University in Partial fulfillment of Master degree
requirements for preventive Dentistry.

Signature:
Name of the supervisor:
Supervisor degree:
Date:

2
 Contents Page No.
Supervisor certification 2

Table of list

List of table

List of abbreviations

1.Introduction of periodontal disease

2.Overview of periodontal disease

2.1 Definition of periodontal disease

2.2 Pathogenesis

2.3 Sign and symptom of periodontal disease

2.4 Classification of periodontal disease

3
2.5 Etiological & risk factors of periodontal disease

3. Prevention strategies of periodontal disease

3.1 Awareness and education

3.2 Daily oral hygiene

3.3 Healthy life style

3.4 Management of systemic condition

3.5 Regular dental visit

4.Biological strategies for prevention: probiotic and

vaccine

5.Prevention of peri-implant disease

6. Phases of the treatment of periodontal diseases

6.1 Phase I or the nonsurgical phase

4
 6.2 phase II or surgical therapy

6.3 Suppurative phase of periodontal therapy

7. conclusion

8.Refrences

List of tables
Table Page number
Table 1 Classification of periodontal disease: 9
staging
Table 2 Classification of periodontal disease: 10
Grading
Table 3 Practical antimicrobial periodontal 43
therapy

List of Abbreviations
IL_1B Interleukin-1B
TNF-A Tumor necrosis factor alpha
MMPS Metalloproteinases
GTR Guided tissue regeneration
CAL Clinical attachment loss
RBL Radiographic bone loss
PD Pocket depth
RCT Randomized clinical trails
VAS Visual analog scale
PI Plaque index
GI Gingival index
IPT Initial periodontal therapy
LAP Localized aggressive periodontitis
dPTFE Dense polytetrafluoroethylene
EPTFE Expanded polytetrafluoroethylene

5
1.Introduction to periodontal disease
The periodontal diseases are highly prevalent and can affect
up to 90% of the worldwide population. Gingivitis, the mildest
form of periodontal disease, is caused by the bacterial biofilm
(dental plaque) that accumulates on teeth adjacent to the gingiva
(gums). However, gingivitis does not affect the underlying
supporting structures of the teeth and is reversible. Periodontitis
results in loss of connective tissue and bone support and is a
major cause of tooth loss in adults. Periodontitis not only
affecting periodontal health but also having implications for the
patient's general health and wellbeing (Chapple,2022). Because
of this broad impact, it clearly needs increased recognition and
attention for the overall health of mankind (Tonetti,2017). and
with this, health professionals themselves need to gain more
awareness on periodontal disease and its effect on the overall
health of their patients.
In addition to pathogenic microorganisms in the biofilm, genetic
and environmental factors, especially tobacco use, contribute to
the cause of these diseases. Common forms of periodontal
disease have been associated with adverse pregnancy outcomes,
cardiovascular disease, stroke, pulmonary disease, and diabetes
etc. Prevention and treatment are aimed at controlling the
bacterial biofilm and other risk factors, arresting progressive
disease, and restoring lost tooth support.
It is widely accepted that the most common and important
diseases of the oral cavity (gingivitis and periodontitis, dental
caries, and oral cancer) are preventable. Based on a large body
of scientific evidence, a number of preventive strategies exist,
that, if routinely implemented, will prevent these diseases in
most individuals. Unfortunately, while most preventive
strategies are theoretically simple to understand, they are often
difficult to employ in practice at individual and public health
level.It is our hope that after reading this volume, the
practitioner will have improved their under- standing of
periodontal disease prevention in order to better educate their
patients and incorporate evidence-based preventive strategies in
their practice to help prevent these costly and impactful
diseases.

6
2.Overview of periodontal disease
2.1 Definition
Periodontal disease is a group of inflammatory conditions affecting the tissues
supporting the teeth, initiated by microbial biofilm and influenced by host
response and environmental factors. It starts as gingivitis and may progress to
periodontitis, characterized by loss of connective tissue and alveolar bone,
potentially leading to tooth loss (Tonetti et al., 2018; Jepsen et al., 2018).
Periodontitis can influence quality of life through psychosocial impacts as a
result of negative effects on comfort, function, appearance, and socialization
(Durham 2013; Needleman 2004), and can lead to tooth loss (Broadbent 2011).

2.2 Pathogenesis
The pathogenesis of periodontal disease involves a dynamic interplay between
microbial biofilm and the host immune response. The disease initiates with
dysbiosis of the oral microbiota, particularly involving keystone pathogens like
Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia,
which disrupt the host-microbe balance and trigger inflammatory pathways
(Hajishengallis, 2020). The dental plaque biofilm acts as a protective matrix for
pathogenic bacteria, allowing chronic infection and resistance to immune
defenses (Lamont et al., 2023).
The host immune response, although intended to control infection, releases
inflammatory mediators such as interleukin-1β (IL-1β), tumor necrosis factor-
alpha (TNF-α), and matrix metalloproteinases (MMPs), which contribute to
tissue destruction and alveolar bone resorption (Xiao et al., 2024). Systemic
factors such as diabetes and smoking exacerbate this inflammatory response,
further modulating disease progression (Zhou et al., 2021).

2.3 Sign and symptom:

Periodontal disease presents with both clinical signs and subjective symptoms
that reflect underlying inflammation and tissue destruction. Key signs include
gingival redness, swelling, and bleeding on probing—early indicators of
gingivitis (Kinane et al., 2017). As the condition progresses to periodontitis,
additional clinical features appear, such as periodontal pocket formation,
clinical attachment loss, and radiographic evidence of alveolar bone resorption
(Papapanou et al., 2018).Patients may report symptoms such as halitosis (bad
breath), tooth mobility, discomfort during chewing, and gingival recession. In
advanced stages, tooth exfoliation may occur due to severe bone and ligament

7
destruction (Tonetti et al., 2018). The absence of pain in early stages often leads
to delayed diagnosis, emphasizing the need for routine periodontal evaluation.

2.4 Classification of periodontal disease

I. Gingival disease
A. Plaque induced can be modified by systemic factors, medications, and
malnutrition.
B. Non-plaque induced gingival lesions include diseases of bacterial, viral, or
fungal origin, genetic manifestations of systemic conditions, traumatic lesions,
and foreign body reactions
2.Forms of periodontitis
a. Necrotizing periodontal disease
b . Periodontitis as manifestation of systemic disease
c. Periodontitis
Staging and Grading Periodontitis:
The 2017 World Workshop on the Classification of Periodontal and Peri
Implant Diseases and Conditions resulted in a new classification of periodontitis
characterized by a multidimensional staging and grading system. The charts
below provide an overview.

PERIODONTITIS: STAGING
Staging intends to classify the severity and extent of a patient’s disease based on
the measurable amount of destroyed and/or damaged tissue as a result
of periodontitis and to assess the specific factors that may attribute to the
complexity of long-term case management.
Initial stage should be determined using clinical attachment loss (CAL). If CAL
is not available, radiographic bone loss (RBL) should be used. Tooth loss due to
periodontitis may modify stage definition. One or more complexity factors may
shift the stage to a higher level.

8
 Table 1
Periodontitis Stage I Stage II Stage III Stage IV

Interdental 1-2mm 3-4mm ≥5 mm ≥5 mm

CAL (at site
Severity of greatest
loss)
RBL Coronal third Coronal Extending to Extending to
(<15%) third (15% middle third middle
- 33%) of root and third of root
beyond and beyond
Tooth loss No tooth loss No tooth ≤4 teeth ≥5 teeth
loss
(due to
periodontitis
)
.Local .Max. probing .Max. In addition In addition to
depth probing to stage III
Complexity
depth ≤5 complexity :
≤4 mm Stage II
mm complexity: .Need for
.Mostly
. Mostly complex
horizontal Probing
horizontal rehabilitation
depths ≥6
bone loss due to :
bone loss mm
-
.Vertical
Mastiocatory
bone loss ≥3
dysfunction
mm
-secondary
.Furcation
occlusal
involvement
trauma (tooth
Class II or
mobility
III
degree
.Moderate degree ≥2)
ridge defects
-severe ridge
defects
-Bite collapse
,drifting
,flaring
- < 20
remaining
teeth

9
 (10 opposing
pairs )

Add to stage For each

as descriptor stage,
Extent and
describe
distribution
extent as:
•
Localized
(<30% of
teeth
involved);
•
Generalized;
or
•
Molar/incisor
patter

PERIODONTITIS: GRADING
Grading aims to indicate the rate of periodontitis progression, responsiveness to
standard therapy, and potential impact on systemic health.
Clinicians should initially assume grade B disease and seek specific evidence to
shift to grade A or C.
Table 2
Progressio Grade A: Grade B: Grade C:
n Slow rate Moderate Rapid rate
rate

Primary Direct Radiographi <2 mm over 5 ≥2 mm over criteria

criteria evidence of c bone loss years 5 years progression
progression or CAL bone loss or
Wheneve CA
r %bone loss <0.25 0.25 to 1.0 >1.0
available, \age

10
 direct Indirect Case Heavy biofilm Destruction Destruction
evidence evidence of phenotype deposits with low commensurat exceeds
should be progression levels of e with expectations
used destruction biofilm given
deposits biofilm
deposits;
specific
clinical
patterns
suggestive
of periods
of rapid
progression
and/or
early onset
disease
Grade Risk factor Smoking Non smoker <10 ≥10
modifiers cigarettes/da cigarettes/da
y y
Diabetes Normoglycemic/n HbA1c HbA1c
o diagnosis of <7.0% in ≥7.0% in
diabetes patients with patients
diabetes with
diabetes

2.5 Etiological and risk factors of periodontal disease

The role of different bacterial species in the subgingival biofilm as the
primary etiological factor in periodontitis is indisputable. The microbiological
characteristics of periodontitis show significant changes from those in
periodontal health with co-association of different organisms into consortia,
representing the critical shift of the oral microbiome from symbiotic states to
dysbiotic ones (Mira et al.,2017).9 It is worth noting that host response plays an
important role in the pathogenesis of periodontal diseases. Indeed, the
dysregulation of immuno-inflammatory pathways is crucial for persistent
periodontitis lesions (Cekici et al.,2014).
It is well noted that microbe-host interaction is the key element in the
pathogenesis of periodontal diseases. However, various risk factors do influence
and modify this interplay (Genco &Borgnakke 2013). Among them,
nonmodifiable risk factors/indicators include genetic profiles, gender, age and
some systemic conditions (such as leukaemia and osteoporosis). There are
also modifiable risk factors/indicators, including lifestyle factors, e.g. smoking
and alcohol, metabolic factors Abnormal habit: like unilateral mastication ,

11
clenching , bruxism, abnormal biting habit, e.g., obesity, metabolic syndrome
and diabetes, dietary factors, e.g. dietary calcium and vitamin D deficiency,
socioeconomic status and stress. In addition, local factors, such as levels of
plaque and/or calculus, furcations, enamel pearls, root grooves and concavities,
open contacts, malpositioned teeth, wearing dentures, and overhanging and/or
poorly contoured restorations may increase the risk for periodontal diseases.

3. Prevention strategies of periodontal disease :

3.1 Awareness and education
- The primary preventive action at community level involves health education
programs to raise awareness among individuals at different stages of life, about
the necessity and importance of daily oral hygiene care. To achieve this, these
programs need to be implemented in different settings, such as schools and both
public and private healthcare services, to reach the widest audience possible.
However, the challenge to preventive actions at population level is often related
to access to healthcare services. Implementing effective educational programs to
promote oral hygiene practices and providing easy access to dental services
pose significant challenges. The lack of resources, adequate infrastructure, and
awareness within communities can limit the effectiveness of preventive
interventions. preventive approach to oral health care demands behavior
modification through effective patient education, which requires time, effort,
and repetition. As such, every opportunity to educate and motivate patients
should be seized in order to implement positive behavioral changes. Patients
should be given personalized, site specific oral hygiene instructions for biofilm
control and to improve their oral health, including periodontal health. It is not
uncommon for patients presenting with poor plaque control and the presence of
disease to report brushing and flossing multiple times daily. If suboptimal
plaque control is evident, the patient should be asked to demonstrate biofilm
control (toothbrushing, flossing, etc.) in front of a mirror so that both the patient
and the clinician can see their oral hygiene techniques. The patient should then
be taught proper biofilm control techniques with a demonstration in their own
mouth in front of a mirror. Ideally, unless emergency treatment is required,
patients should be given at least 1 or 2 weeks to improve their oral hygiene, to
control biofilm and reduce periodontal inflammation, and to appreciate how
meticulous biofilm control can positively impact their oral health before any
periodontal treatment is rendered.

12
•Preventing periodontal disease typically uses an individual approach and
focuses on two general areas: (1) promoting oral hygiene activities such as tooth
brushing, flossing, and using mouth rinse; and (2) recognizing an
individual’s risk factor(s) and recommending intervention for modifiable risks
such as smoking. However, population-based strategies for preventing
periodontal disease have been limited. An approach documented has been “mass
awareness” campaigns (Zuman et al.,2015; Gholami et al.,2014; Leous &
Kazeko ,2006; Martensson et al.,2006; Kay &Locker,1996). In Japan, there is a
national promotional effort called the 8020 Campaign. (Saito & Kawaguchi
,2002). This population-based public awareness campaign is focused on
encouraging the Japanese people to keep at least 20 teeth by age 80. The
program is designed for periodontal disease prevention and is one of few large-
scale public health approaches implemented globally.
-Community preventive strategies for PD should not be isolated from health
programs with the aim of establishing healthy lifestyles. Due to its status as a
low-grade inflammatory disease, it should be considered, especially in more
vulnerable populations. Therefore, community strategies public and private
health systems need to provide community strategies that involve oral health in
risk control programs for cardiovascular and metabolic diseases, pregnant
women, etc .Furthermore the prevention of PD should be integrated into the
strategies for promoting and communicating information on acquiring healthy
lifestyles, such reducing tobacco consumption, adopting healthy nutrition,
physical exercise, improvement in sleep, moderate alcohol consumption, and
strategies to manage stress(Kirchhof et al.,2018). Government and private
entities, scientific associations and universities should act together to improve
the periodontal health and well-being of the population. Strategic alliances with
Dental Product Companies are necessary to achieve the Distribution of free or
affordable oral hygiene products to underprivileged areas.
-individual approach to prevention of periodontal disease draws upon a
biological and behavioral model focusing on mechanical biofilm control,
reducing putative bacterial load, and eliminating high risk behaviors like
smoking. Consequently, this traditional clinical approach has limited
applicability to make any changes in periodontal disease prevalence at the
community level. The traditional approach to prevent periodontal disease is
costly and can represent a significant economic burden, even in high-income
countries.
-Effective population-based tobacco control interventions have included tobacco
price increases, high-impact anti-tobacco mass media campaigns, and policy

13
actions implementing comprehensive smoke-free public spaces. These public
health approaches have decreased smoking population rates and reduced
tobacco-associated diseases and mortality across diverse race/ethnic and
socioeconomic groups.
-There are many examples of public health initiatives that have helped to drive
down the prevalence of serious medical conditions. For example, antismoking
educational campaigns and, most importantly, no-smoking laws have greatly
reduced the number of smokers as well as the diseases that often result from
smoking, such as lung cancer. However, more action at the public health level is
needed in order to motivate behaviors that would prevent periodontal disease.
Indeed, most action in this regard has occurred at the individual, patient-focused
level.
-An online application initiative (perio-awareness) was published to promote
awareness about the prevention of PD. The application evaluates 12 parameters
(“6 gold and 6 silver Questions”) that patients can assess their periodontal signs
and symptoms. Based on an algorithm, recommendations are given to
encourage the search for a professional diagnosis and an appropriate
patient/professional interaction. The recommendations provided by this
application are based on the survey finding about the possible characteristic
parameters/situations/habits of users (Duque et al.,2023)
Some recommendations:
1-It is necessary to increase efforts to raise awareness about PD so that health
authorities pay more attention to the importance of periodontal health.
2-The participation of leaders in the region, who participate in public health
policy decisions is required to link periodontal health into risk factor control
programs and adherence to healthy lifestyles.
3-The dental office must become an additional setting where patients can learn
about healthy lifestyles.
4-Establish a collaboration network among dental and medical professionals to
share knowledge, research findings, and educational resources on periodontal
and systemic health interrelations.
5-Emphasize Personalized Oral Hygiene Education: Stress the importance of
tailored oral hygiene instructions in professional development sessions for
dental practitioners, catering to the diverse needs of patients including those
with special needs.

14
6-Invest in studies exploring the impact of mobile health applications, tele-
dentistry, and social media on oral health awareness and self-care
7-Execute comprehensive campaigns across community settings such as
schools, workplaces, and public spaces, using both traditional and digital media
to highlight the risks of PD and its impacts on systemic health. Engage local
influencers to help with extending the reach and effectiveness of campaigns

Recent technologies
Teledentistry is a broad term encompassing multiple methods and a wide range
of virtual technologies, primarily computers and mobile devices. Overall,
teledentistry has been proposed as an effective tool for remote screening, caries
detection8, diagnosis, counseling, treatment planning, and guidance (Irving et
al.,2018; Fernadez et al.,2021). People can see dentists online without
physically meeting with them by using teledentistry apps (Sidabutar etal.,2024).
Although some recent systematic reviews have focused on the use of mobile
Health to improve oral health knowledge and gum health or the use of
reminders to improve orthodontic patient hygiene. Virtual technology support
that teledentistry may help prevent and promote oral health. Starting with
traditional written textbooks that have been in use for many years, current
virtual technologies offer many new possibilities for healthcare and dentistry.
This is because of the widespread use of telecommunications .
teledentistry can provide structured training and schedule these training
activities to be specific and longer. It also allows for the repetition and
reinforcement of training between dental appointments, with great potential to
improve clinical outcomes.
3.2 Daily oral hygiene
Plaque management consists of the use of mechanical procedures and chemical
agents that retard the formation of plaque. Mechanical methods of plaque
prevention include toothbrushing, oral hygiene, and professional prophylaxis for
interdental washing. The most effective method of plaque control at present
appears to be mechanical plaque control. Chemical plaque regulation was used
only as an extension and not as a replacement to the mechanical means. Further
improve the performance of plaque management programs using anti-plaque
agents as an adjuvant to mechanical plaque control.(Vander &Slot ,2015).
-Daily habits play a crucial role in the effective control of supragingival biofilm.
Although brushing is considered an essential method, there are still some

15
questions related to the recommendation of specific characteristics of manual
brushes, use of electric brushes, and the choice of interproximal devices. In a
systematic review evaluating mechanical control in individuals undergoing
periodontal maintenance, 80% of studies comparing manual and electric
toothbrushes found no significant differences between them. However, the
authors emphasize the lack of robust evidence due to the limited number of
studies(Slot et al .,2020). As regards bristle design, toothbrushes with tapered
tips showed superior reductions in the plaque index and gingival bleeding
compared with round-tipped brushes. Relative to electric brushes, oscillating-
rotating powered toothbrushes exhibited a slight difference in plaque control
and improvement in gingival health when compared with frequency sonic
powered toothbrushes (Sluijs et al.,2023). Moreover, more importantly than a
technique, it should be emphasized that strategies must be taught and
communicated to patients according to individual characteristics or their
stratification according to risk.
-A multicenter study on oral health behavior in South American adults showed
that 84.2% of subjects brushed their teeth twice a day or more, but only 17.7%
reported interproximal cleaning daily (Gomez et al.,2018). Interproximal
cleaning devices, especially dental floss, are more effective when combined
with manual brushing than manual brushing alone. There is limited and
inconsistent evidence for tooth cleaning sticks and oral irrigators (Worthington
et al.,2019), although interdental cleaners with rubber bristles were preferred by
study participants (Weijden et al.,2022). When prescribing mechanical control
items, patient skills and preference should be considered, especially in older
adults dealing with xerostomia and have low manual ability.

Traditional plaque control (gold stander)

-Traditional plaque control measures, such as toothbrushing and flossing play a
pivotal role in preventing periodontal diseases. Combining flossing with
toothbrushing significantly reduces gingivitis and plaque accumulation
compared to brushing alone, emphasizing their synergistic effectiveness in
maintaining oral health (Hennysutrisman ,2024).
-A recent prospective cohort study of 2819 participants over 11 years reported
that the use of power toothbrushes was associated with statistically significant
and clinically relevant reductions in clinical attachment loss and probing pocket
depths as well as higher numbers of remaining teeth (Pitchika V et al.,2019).

16
-The application of power toothbrushes is frequently combined with user‐
friendly wireless remote displays in order to structure and improve the duration
of the brushing procedure, which might help to further improve efficacy (Janusz
K et al.,2008).
- Proper instructions should be provided for every toothbrush, including
powered ones, in order to prevent injury to both hard and soft oral tissues

HOW OFTEN AND FOR HOW LONG SHOULD WE BRUSH?

- In daily dental practice, it is generally recommended to brush twice daily with
a fluoride‐containing toothpaste for 2 minutes52 in order to eliminate plaque, to
prevent caries and gingivitis, and also to give a feeling of oral freshness (Davies
RM &Davies GM ,2003).

WHAT ARE THE ADVERSE E VENTS OF TOOTHBRUSHING?

-commonly discussed concern related to toothbrushing is the development of
gingival recessions as a negative side effect(Rajapaske PS et al.,2007;Oliveria et
al.,2014). Toothbrushing factors that might be associated with gingival re‐
cession are toothbrushing frequency, a horizontal or scrub tooth‐ brushing
method, bristle hardness, toothbrushing duration, and the frequency of changing
a toothbrush (Heasman et al.,2015 ).

Interdental cleaning aid:

The choice of interdental cleaning product is usually made individually
depending on patient preference. The size and shape of the interdental space,
contour of the gingiva, tooth alignment, dexterity, and motivation of the patient
all influence the type of interdental device to use
Example on interdental cleaning aid:
1.Dental floss
A more lubricious dental floss can be passed over the approximal contact with
less pressure to reduce the risk of papillary trauma (Dorfer et al.,2001). the use
of dental floss should be recommended, because it is still useful for interdental

17
cleaning, especially when anatomic considerations preclude the use of more
effective interdental cleaning devices that will not pass through the
interproximal area without trauma (Chapple et al.,2015 ).

2. Interdental brushes
- Interdental brushes are cylindrical or conical, angled or straight, and they vary
with respect to the stiffness of filaments. Areas that are not accessible by a
toothbrush, like the central part of the interdental space and the embrasure, can
be reached effectively by interdental brushes(slot et al.,2008 ;Poklepovic et
al.,2013 ).Especially in teeth with attachment loss, the concavities in the
approximal root surfaces are not accessible for plaque removal using dental
floss or woodsticks
-Although interdental brushes appear to be superior to other interdental cleaning
devices, additional reduction of gingivitis and plaque scores of approximately
30% can be expected when they are used as adjuncts to toothbrushing compared
with toothbrushing alone(salzer et al.,2015 ).

3. Sticks and twigs, composed of bone, ivory, metal, plastic, quills, wood, and
other substances, have been used for cleaning tooth surfaces and interdentally
since prehistoric times (Christen 2003). The meswak (or miswak) is one of the
most widely used tooth cleaning sticks (Saha 2012)
Dental woodsticks have a trapezoidal profile and are slightly curved along their
length. They are manufactured from long fiber, shatter proof wood, and are
available in different sizes. Their application is similar to interdental brushes.
However, they have limitations with respect to cleaning root concavities and
insertion at a correct angle in the most posterior interdental spaces.
-However, gingival bleeding can be reduced significantly by woodsticks
compared with toothbrushing alone. This might be a consequence of the
physical stimulation of the swollen papilla by the woodstick.
-The occurrence of gingival bleeding following the use of wood sticks can be
used gingival health assessment .Gingival self‐assessment has been
demomonstrated to be an effective method. The presence of bleeding provides
immediate feedback on the level of gingival health. The dental care professional
can therefore easily demonstrate the gingival condition to the patient, using an
interdental bleeding index to quantitate the clinical manifestation. This
monitoring could encourage patients to include woodsticks as part of their oral

18
hygiene regimen(Vander et al.,2015). to increase patient motivation and
awareness.
4. Oral irrigators
Oral irrigation is safe and effective for a wide variety of patients, including
those in periodontal maintenance; those with gingivitis, orthodontic appliances,
implants, or diabetes; and those who are noncompliant with floss. Clinical
outcomes include reductions of plaque, calculus, gingivitis, bleeding on
probing, probing depth, periodontal pathogens.
-Oral irrigation with water under pressure has been available for just over fifty
years (Lyle 2012), and the benefits are described as the removal of biofilm from
tooth surfaces and bacteria from periodontal pockets.Oral irrigators are designed
to flush away loosely adherent plaque through the mechanical action (shear
forces) of a stream of water Applying chlorhexidine by an oral irrigator seems
to be more effective than water with regard to plaque and gingivitis(Flemming
et al.,1990) (Lang et al.,1981).

- A direct comparison of an oral irrigator vs an interdental brush, both in

conjunction with manual toothbrushing, showed that the oral irrigator removed
significantly more plaque from tooth surfaces than interdental brushes after a
single use(Lyle DM et al.,2016), and were more effective in reducing gingival
bleeding over 2 weeks(Goyal CR et al.,2016).
- For interdental cleaning, interdental brushes are the most effective for
periodontitis patients. Other tools like floss, woodsticks, or rubber cleaners may
be used if brushes don’t fit well. Oral irrigators are less effective for wide
spaces caused by attachment loss but might help along the gum line

-After all oral hygiene procedures (such as tooth brushing) are ceased, the
biofilm begins to develop on the teeth within 24 h and causes gingivitis in10–21
days. Thorough tooth cleaning returns the gingiva to a healthy condition in
about 1 week.166 Control of the periodontal biofilm with professionally
administered oral hygiene can slow or stop periodontitis and tooth loss for many
years.

19
Chemical plaque control
evidence shows that the use of chemical plaque control agents in toothpastes
and mouthwashes is effective in preventing accumulation of plaque and in the
prevention and treatment of periodontal diseases.
IDEAL PROPERTIES OF ANTIPLAQUE AGENTS:
1.Elimination of pathogenic bacteria
2.prevent development of resistant bacteria
3. exhibit substantivity
4.safety
5.reduction in plaque and gingivitis
6.no staining or alteration of taste
7.easy to use and inexpensive
8.no systemic effect

-Chlorhexidine (CHX)
is a bisbiguanide with bacteriostatic and bactericidal effects (Davies
,1973)[25].It is the most studied and most effective anti-plaque and anti-
gingivitis agent and is considered the “gold standard” anti-plaque agent(Varoni
et al., 2012) . The mechanism of action of CHX is dose-dependent. It is
bacteriostatic at very low concentrations (0.02–0.06%) and bactericidal at
higher concentrations (0.12–0.20%) . In addition to its immediate bactericidal
effect, CHX also binds to the oral mucosa resulting in a slow and prolonged
antibacterial effect . CHX is widely used in dentistry. It is available as oral
rinses (0.02–0.3%), gels (0.12–1%), sprays (0.12–0.2%), and dental varnishes
(1%, 10%, 40%). The long-term use of CHX is associated with local adverse
effects of temporary alteration of taste (dysgeusia) and tooth pigmentation.
The 0.2% CHX mouthwash was observed to significantly reduce plaque,
gingival inflammation,and gingival scores. Rinsing with 10 mL of either
solution one time a day for a period of six weeks showed to be more effective in
controlling both plaque and gingivitis compared to brushing alone.
In recent years, the use of newer approaches and technology to improve the
efficacy of CHX have been studied. Low-intensity direct current (DC) has

20
shown to promote CHX antimicrobial efficacy against P. gingivalis within a
biofilm. A significant increase in the 0.2% CHX efficacy against P. gingivalis
was seen when applying 10 mA current.This effect is called a bioelectric
phenomenon. No effect of electric current was seen with 1.5 mA(Lasserre et
al.,2015) .

-Cetylpyridinium Chloride
is a cationic quaternary ammonium compound with a broad-spectrum
antimicrobial activity. It inhibits cell growth and causes cell death by interacting
with the cell membrane and causing leakage of cellular components CPC
mouth rinses produce a small but significant adjuvant reduction of plaque and
gingival inflammation when combined with toothbrushing (Haps et al.,2008).
A novel mouth rinse combining CPC and hyaluronic acid (HA), which is a
natural compound with anti-inflammatory and bacteriostatic properties and
prevents growth of plaque, showed similar effects to CHX in preventing plaque
accumulation and no difference in preventing gingivitis
-In a different study, the use of a mouthwash containing CPC and tranexamic
acid (TXA), a synthetic derivative of the amino acid lysine with antifibrinolytic
activity, was tested in patients with gingivitis. It showed a statistically
significant reduction of supragingival dental plaque and alleviated the
symptoms of gingival bleeding, particularly, of bleeding on probing (BOP) over
a period of six weeks (Lee et al.,2017).

-Stannous Fluoride
Adding an SnF2 toothpaste to the daily oral care regimen has been shown to
have multiple oral health benefits including reduction of dental calculus
buildup, dental plaque, gingivitis, staining, and halitosis
-Furthermore, SnF2 was found to have both direct and indirect effects on the
development of gingivitis. The direct effect referred to an anti-inflammatory
action while the indirect effect—to the amelioration of gingivitis caused by
plaque reduction (Sensabaugh et al.,2009).
-A toothpaste (Colgate Total SF) containing 0.454% SnF2 stabilized with 1%
zinc phosphate has been shown to significantly reduce plaque, gingivitis, dentin
hypersensitivity, and extrinsic stains in both in vitro and clinical studies
-Zinc

21
is added to toothpastes and mouth rinses as an antibacterial agent to control
plaque, to reduce oral malodor by inhibition of volatile sulfur compounds, and
to reduce calculus formation through crystal growth modification/inhibition. It
has a broad-spectrum antibacterial activity (Finney et al.,2003) and acts mainly
by targeting the cytoplasm and glycolytic enzymes of bacterial cells and by
inhibiting the process of glycolysis (Phan et al.,2004).

-Licorice
the root of Glycyrrhiza glabra, is a herb native to Asian and Mediterranean
countries. Due to its sweet taste, licorice is used as a natural sweetener and
flavoring agent in foods, drinks, and candies. In addition, licorice roots have
been used for centuries in traditional Chinese medicines and Ayurveda due to its
numerous health benefits (Messier et al.,2012).
-The pharmacological effects of licorice are attributed to its rich secondary
metabolites like glycyrrhizic acid and glycyrrhetic/glycyrrhetinic acid (GA) (Li
et al.,2014). Licorice has many pharmacological benefits, including
antimicrobial, antiviral, antiulcer, anti- inflammatory, hepatoprotective, and
immunoregulatory effects (Shin et al., 2007).
-A recent study in rats showed GA to inhibit periodontal destruction.
Licorice is available in the form of candies, lollipops, capsules, tablets, and
liquid extracts. It is listed as “generally recognized as safe” by the FDA in the
USA. It is considered safe for individuals who are not sensitive to glycyrrhizin
and when consumed in small quantities. According to the WHO, 100 mg/day of
licorice can be consumed safely without any side effects (Messier et al.,2012).
However, studies show that continuous exposure to high doses of licorice,
particularly to glycyrrhizin, can lead to hypokalemia, severe hypertension,
metabolic alkalosis, and edemas due to its hypermineralocorticoid-like effect
(Isbrucker et al.,2006).

-Curcumin
is a natural polyphenol derived from the plant Curcuma longa Linn, commonly
known as turmeric. Though turmeric is cultivated principally in India, China,
and other Asian countries, it is also common in other parts of the world
(Ravindran et al.,2006). It is used as a spice in cooking, as a food colorant, and
in cosmetics. It has also been traditionally used in the Chinese medicine and

22
Ayurvedic medicine for thousands of years to treat bacterial infections and
inflammatory diseases (Tilak et al.,2004).
-The use of a 0.1% curcumin mouthwash (prepared by dissolving the curcumin
extract in distilled water) in chronic gingivitis patients was found to be
comparable to the effect of a 0.2% CHX mouthwash in plaque reduction and
better than that of a CHX mouthwash in reducing gingival inflammation and in
the reduction of reactive oxygen metabolites. While a non-significant difference
was seen in plaque index scores between curcumin and CHX groups, a
significant reduction in the gingival index was seen in the curcumin group
compared to the CHX group. The results of the clinical study thus suggest
curcumin mouthwashes as a potential alternative to CHX mouthwashes because
of its anti-inflammatory and antioxidative properties (Arunachalam et al.,2017).
-LIPPIA SIDOIDES
•mouthwash
•northeast of Brazil.
Studies indicated that these major components had
shown potent antimicrobial activity against fungi and
bacteria and reduced the severity of gingivitis and
bacterial plaque.
A randomized controlled trial assessed the short-term effects of a mouthrinse
containing Lippia sidoides EO on gingival inflammation and bacterial plaque.
The study involved 55 patients who used either the Lippia sidoides-based
mouthrinse or a 0.12% chlorhexidine mouthrinse over a 7-day period. Results
demonstrated significant reductions in plaque index, gingival index, and
gingival bleeding index scores in both groups, with no statistically significant
differences between them. This suggests that Lippia sidoides mouthrinse is as
effective as chlorhexidine in reducing bacterial plaque and gingival
inflammation (Botelho et al. ,2008)

Another clinical trial evaluated the effect of a gel containing Lippia sidoides EO
on plaque and gingivitis control. Thirty patients were randomly assigned to
three groups: Lippia sidoides gel, chlorhexidine gel, and placebo. After three
months, both the Lippia sidoides and chlorhexidine groups showed significant
reductions in plaque and gingivitis compared to the placebo, with no significant
difference between the two active treatments. This indicates that Lippia sidoides

23
gel is an effective herbal alternative for controlling plaque and gingivitis (Feres
et al. 2013)

A systematic review analyzed multiple studies on Lippia sidoides-based

products, including mouthrinses, toothpastes, and gels. The review found that
these products were effective in reducing dental plaque and calculus formation,
as well as clinical signs of gingivitis. In some studies, Lippia sidoides products
showed comparable or even superior results to conventional agents like
chlorhexidine and cetylpyridinium chloride. However, the review also noted
methodological limitations in the included studies, suggesting the need for
further high-quality clinical trials to confirm these findings ( Barbosa et al.
2021)

PERIOCHIP
orange brown, biodegradable, rectangular chip rounded at one end that has an
active ingredient of chlorhexidine gluconate (2.5 mg) that is released into the
pocket over a period of 7 to 10 days. approved by the FDA as an adjunct to SRP
procedures for the reduction of probing pocket depth or as part of a routine
periodontal maintenance program. suppress the pocket flora for up to 10- 11
weeks post application. A randomized controlled trial evaluated the efficacy of
PerioChip when used alongside SRP in patients with moderate to severe
periodontitis. The study found that while both SRP alone and SRP combined
with PerioChip led to significant improvements in clinical parameters, there was
no statistically significant difference between the two groups. However, the use
of PerioChip alone resulted in less improvement, highlighting its role as an
adjunct rather than a standalone treatment (Yechiel et al. (2014).

-In SR, complementary antiseptics in mouthwashes and toothpaste have been

reported to provide statistically significant reductions in gingival, bleeding and
plaque indices, and combination of the two has shown better results (Figuero et
al.,2020). Recent studies have suggested reevaluation of oral health prevention
and promotion. Recent research has focused on the effectiveness of fluoride
toothpaste and other antimicrobial agents such as stannous fluoride-based
toothpaste and sodium bicarbonate toothpaste. A SR found that stabilized SnF2
toothpaste had a positive effect on reducing the accumulation of dental calculus,

24
dental plaque, gingivitis, stains and halitosis (Johannsen et al.,2021; Taschieri et
al.,2022). This intervention should be explored as a preventive aid in the
progression of plaque-induced gingivitis to periodontitis.
Essential oils and cetylpyridinium chloride (CPC) mouthwash were the active
ingredients most frequently used in preventing gingivitis. Overall, studies have
shown improvements in the clinical parameters evaluated(Figuero et al.,2020).
When compared with a placebo solution, CPC demonstrated good efficacy for
plaque and gingival inflammatory parameters on interproximal surfaces(Langa
et al.,2021).Recently, a multi-component oral care regimen with a zinc
formulation (Dual) and CPC + In mouthwash was shown to be effective in
reducing gingival inflammation and supragingival biofilm in patients with
gingivitis (Amaral et al.,2024).
-In adolescence, many individuals in the region undergo orthodontic treatment
without supervision for periodontal health, which is a decisive moment for
future periodontal health and bone support. A SR revealed that orthodontic
manual brushes outperformed conventional manual brushes in plaque removal,
with no significant difference in gingival bleeding(Marcal et al.,2022). Electric
toothbrushes, compared with manual types, demonstrated a significant reduction
in both plaque and gingival indices(Sivaramakrishnan et al.,2021). SR
comparing different mouthwashes for patients with fixed orthodontic appliances
revealed similar results, indicating that chlorhexidine was effective in reducing
biofilm and signs of gingival inflammation(Karamani et al.,2022;Ren et
al.,2023) .

- A study (Shakhsi et al.,2024) we assessed the synergic effects of Xylitol,

EDTA and MSM in a chewing gum in comparison with chlorhexidine
mouthwash. This study was a crossover, randomized clinical trial. Twenty-four
patients were divided in two groups randomly. At the baseline scaling and root
planing was done for each patient. Group1 used chlorhexidine mouthwash twice
a day. Group2 used novel chewing gum for 15 min twice a day. After 14 days,
for every patient plaque index, gingival index and sulcus bleeding index were
reevaluated and recorded. Professional brushing was done for patients. 14 days
were considered as wash-out period. After that, method of plaque control of
groups was changed. After 14 days, all patients were reevaluated and recorded
and were compared with previous data. Samples in 2 groups had no significant
difference in age and sex. Paired sample test revealed that there were
significant differences between first and second period for plaque index,
gingival index and sulcus bleeding index in Group1 (P < 0.05). But in Group2

25
there were no differences between first and second period for all indexes. Also
independent sample t test showed that there were no significant differences
between baseline, after first treatment and after second one for all indexes in
both groups (P > 0.05). According to regression model results, type of treatment
had no effect on mean of all indexes. According to our findings which showed
the similar efficiency of novel chewing gum and chlorhexidine mouthwash in
improving and reducing plaque and gingival indexes, we can conclude that
novel chewing gum can be introduced as an effective, cheap and accessible tool
for dental plaque control.

Future Challenges in Chemical Plaque Control

New methods are therefore important for controlling oral plaque-related
diseases in the hour. Probiotics aims at the removal of pathogenic bacteria to
ensure biological plaque regulation. Probiotics have not only antimicrobial
properties but are also able to modulate the immune system into anti-
inflammatory actions(Alshareef et al.,2020). Another field of research is now
being developed for vaccinating oral biofilm-related disease. Further research to
determine the potential use of these agents are of the utmost importance. Natural
products provide structurally diverse substances with a broad range of
biodiversity that may be useful for alternative or adjunctive plaque therapy.
Hence, chemical plaque control, though just an adjunct to mechanical plaque
control, offers promises, challenges, and unexplored arenas (Jafer et al.,2016)

3.3 Healthy life style

a. Dietary factors
There are no nutritional deficiencies that by themselves can cause gingivitis or
periodontitis. However, nutritional deficiencies can affect the condition of the
periodontium and thereby may accentuate the deleterious effects of plaque-
induced inflammation in susceptible individuals. Theoretically, one may
presume that an individual with a nutritional deficiency is less able to defend
against a bacterial challenge as compared with a nutritionally competent
individual (Advisory ,2007).
-There are nutritional deficiencies that produce changes in the oral cavity. These
changes include alterations of the tissues of the lips, oral mucosa, gingiva, and
bone. These alterations are considered to be the periodontal and oral

26
manifestations of nutritional disease.The role of nutrition in periodontal disease
may be related to the effect of nutrition on inflammation.
-Data suggest that diets that contain foods rich in antioxidants are beneficial,
whereas foods that contain high levels of refined carbohydrates are detrimental
to the inflammatory process (Chapple ,2007)
Impact of Macronutriments on Periodontal Diseases
Macronutrients consist of carbohydrates, proteins and fats. These are the
nutrients from the food supply that provide energy to the body and ensure the
proper functioning of its vital functions .Carbohydrates are composed of sugars,
starches and fibers that have different effects on PDs. While sugar and starches
are sources of glucose, fibers are a nondigestible form of carbohydrates (Slavin
&Carlson ,2014). The main sources of carbohydrates are fruits, vegetables,
whole grains, milk, and milk products. While grains and certain vegetables
(potatoes and corn) are rich in starch, sweet potatoes are rich in sucrose. Dark-
green vegetables and fruits are sources of sugars and dietary fiber (Slavin
&Carlson ,2014).
-Depending on the nature of the carbohydrates consumed, the effect on PD will
be different. An excessive consumption of sugar or refined carbohydrates
promoted microbiota dysbiosis that induced an inflammatory reaction and
caused the apparition of PDs (Bosma et al., 2012; Alder et al., 2013) .Dietary
fiber intake is inversely correlated to PD, (Salazar et al. 2018) also concluded
that there was an inverse association between PD and higher consumption of
whole-grains and fruits (Salazer et al., 2018). The protective effect of fibers
against PDs could be explained because they improve glycemic control (Fujii et
al.,2013), which is an established risk factor for periodontitis.

-Fatty acids consist of a straight alkyl chain, terminating with a carboxyl

group. The number of carbons in the chain varies, and the compound may be
saturated (containing no double bonds) or unsaturated (containing at least one
double bond). Milk fat, coconut oil and palm oil are sources of short- and
medium-chain saturated fatty acids (SFA) (4–12 carbons). Long-chain SFAs
(>14 carbons) are found in other vegetable and animal fats. Many food sources
are composed of different fatty acids. Olive oil contains monounsaturated fatty
acids, saturated and polyunsaturated fatty acids (Forouhi et al.,2018) .
The SFA intake could enhance oxidative stress, which has been shown to be
associated with PDs, exerting its effects by damaging cells (Milward et al., 2013
). One other study demonstrated that omega-3 fatty acid (polyunsaturated fatty

27
acids) has a positive impact on PDs whereas SFAs have a negative impact
(Varela et al.,2016 )

Impact of Micronutrients on Periodontal Disease

Micronutrients consist of vitamins, minerals and trace elements. These are
nutrients without energy value, but which are essential for chemical reactions
and therefore vital to the body

-Vitamin A is a group of fat-soluble compounds , Animal-derived food such as

milk, cheese, liver and eggs are sources of preformed vitamin A, whereas
carrots, green leaves, broccoli, ripe mangos, sweet potato, orange-yellow
vegetables, fruits and red palm oil are sources of provitamin A
carotenoids(Najeeb et al.,2016;Dommisch et al.,2018) . According to the UK
National Health Service, men aged from 19–64 years need 0.7 mg/day of
vitamin A compared with 0.6 mg/day for women of the same age . Several
studies have concluded that vitamin A deficiency was linked to the PDs (
Dommisch et al .,2018)
Vitamin A is thought to have a role in the maintenance of the integrity of
epithelial cells (Gondivkar et al.,2019) .
-A major function of vitamin A is to maintain the health of the epithelial cells of
the skin and mucous membranes. A deficiency of vitamin A results in
dermatologic, mucosal, and ocular manifestations. In the absence of vitamin A,
degenerative changes occur in epithelial tissues, thereby resulting in a
keratinizing metaplasia. Because epithelial tissues provide a primary barrier
function to protect against invading microorganisms, vitamin A may play an
important role in protecting against microbial invasion by maintaining epithelial
integrity.

-The vitamin B complex For adults 200 µg/day of vitamin B9, present in leafy
greens and fortified cereals, and 1.5 µg/day of vitamin B12, present in fortified
cereals, meat and fish,are recommended according to the UK National Health
(Dommisch et al., 2018 ) . Few studies have analyzed the association between
vitamin B and PDs. However, deficiency in vitamin B complex results in lower
resistance to bacterial infections, which could explain the role of vitamin B,
particularly vitamin B9, in PDs . In a prospective cohort, Zong et al. analyzed
the potential association between serum vitamin B12 with changes in

28
periodontitis . They demonstrated that an increase in serum vitamin B12 was
associated with a decrease in the clinical parameters of PD (probing pocket
depth, clinical attachment loss and, the tooth loss (Zong et al.,2016).

-Vitamin C (ascorbic acid) can be found in many fruits and vegetables.

According to the UK National Health, a dose of 40 mg/day is recommended for
adults (Dommisch et al.,2018). Several studies have demonstrated that a low
level of vitamin C was associated with PD(Najeeb et al .,2016;Dommisch et
al.,2018) . In a multi-center, randomized, parallel-group, controlled clinical trial
comprising 300 individuals with gingivitis, Shimabukuro et al. concluded that
toothpaste with vitamin C and magnesium salt can reduce gingival
inflammation . Compared with conventional toothpaste, this toothpaste
exhibited a significantly higher activity against reactive oxygen species, which
might be associated with the onset and progression of gingival inflammation
(Shimabukuro et al.,2015)
-Severe vitamin C (ascorbic acid) deficiency in humans results in scurvy, a
disease that is characterized by hemorrhagic diathesis and delayed wound
healing. Scurvy results in the defective formation and maintenance of collagen,
the impairment or cessation of osteoid formation, and impaired osteoblastic
function (Wolbach &Bessey 1942)
-Vitamin C deficiency is also characterized by increased capillary permeability,
susceptibility to traumatic hemorrhages,
-Several studies (electric searches from Pubmed, EMBASE, Cochrane Library
,Web of science)have found that individuals with periodontitis often exhibit
significantly lower serum vitamin C levels compared to healthy controls. For
instance, a systematic review reported that patients with severe periodontitis had
notably lower vitamin C concentrations, suggesting a potential link between
vitamin C deficiency and the progression of periodontal disease There were 716
articles that were retrieved and 14 articles (seven cross-sectional studies, two
case-control studies, two cohort studies, and three randomized controlled trials
(RCT) were selected after reviewing all of the articles. The vitamin C intake and
blood levels were negatively related to periodontal disease in all seven cross-
sectional studies. The subjects who suffer from periodontitis presented a lower
vitamin C intake and lower blood-vitamin C levels than the subjects without
periodontal disease in the two case-control studies. The patients with a lower
dietary intake or lower blood level of vitamin C showed a greater progression of
periodontal disease than the controls. The intervention using vitamin C

29
administration improved gingival bleeding in gingivitis, but not in periodontitis.
Alveolar bone absorption was also not improved. The present systematic review
suggested that vitamin C contributes to a reduced risk of periodontal
disease.,(Staudte et al. (2019)

The efficacy of vitamin C supplementation as an adjunct to non-surgical

periodontal therapy has been investigated. A systematic review concluded that
while vitamin C supplementation may improve bleeding indices in gingivitis, it
does not significantly enhance clinical outcomes such as probing depth
reduction or clinical attachment gain in periodontitis patients (Muniz et al.
(2020)

-A randomized triple-blind study was conducted on 60 patients half receiving

vitamin C supplementation. The VAS score, wound healing index, PI, GI, PD,
and CAL were determined and compared at different time intervals.
Statistical analysis was done for the recorded data. Chi-square test for the
healing index and Friedmann’s test followed by Wilcoxon signed-rank test for
VAS showed statistically significant results (P < 0.05). Friedmann’s test found a
statistically significant (P < 0.05) result for the PI score only in the test group.
Friedmann’s test found the PI to be statistically significant in the test group (P <
0.05). Friedmann’s test followed by Wilcoxon signed-rank test found the PD
and CAL to be statistically significant (P < 0.05) at all different time intervals
Vitamin C’s role in wound healing has been highlighted in periodontal surgical
contexts. A study demonstrated that vitamin C supplementation enhanced
wound healing and reduced postoperative pain following periodontal flap
surgery Yao et al. (2023)

-Vitamin D, which comes mainly from fortified cereals, mushrooms and fish,
enhances the absorption of minerals such as calcium, iron, magnesium,
phosphate and zinc (Schwalfenberg &Genuis 2015). It The UK National Health
recommends intake of 10 µg/day for adults (Dommisch et al., 2018 )

-The vitamin E complex They are the most important lipid-soluble antioxidant
and they prevent lipid peroxidation . The major food sources are vegetable oils,
fortified cereals, nuts, seeds, meats, fruits and vegetables . The UK National

30
Health Service recommends 4 mg/day for men and 3 mg/day for women, but in
the USA the recommended daily intake is 15 mg (Dommisch et al.,2018).

-Vitamin K is a group of vitamins that plays a role in the synthesis of proteins

that are precursors for blood coagulation factors, such as prothrombin and
factors VII, IX, and X(Grober et al.,2014) . It also plays a role in the synthesis
of proteins required for bone metabolism, such as periostin and osteocalcin.
Kale, collards, spinach, and mustard are a source of vitamin K (Najeeb et
al.,2016). Vitamin K deficiency is thought to be associated with gingival
bleeding;

-Calcium is essential for the maintenance and formation of calcified tissues

such as bone or teeth. The recommended daily intake for adults 19–64 years of
age is 700 mg according to the UK National Health Service(Dommisch et
al.,2018) . It is present in milk products, eggs, fish, leafy vegetables, seeds and
nuts (Najeeb et al.,2016).

-Magnesium, found mainly in cereals, nuts, seeds cocoa, soybeans, spinach,

marine vegetables and tomatoes, is also essential for the maintenance and
formation of calcified tissues such as bone or teeth, but its association with
periodontal health is unclear (Najeeb et al.,2016; Dommisch et al.,2018).

-Iron plays a crucial role in oxygen transport by hemoglobin. It is also an

essential cofactor for many enzymes, whose function is reduced if there is an
inadequate supply of iron. The recommended daily dose of iron for men aged
from 19–64 years old and for women aged from 50–64 years old 8.7 mg, and for
women aged from 19 to 50 years, it is 14.8 mg according to the UK National
Health Service (Dommisch et al., 2018). Rich food sources of iron are fish
(salmon and tuna), red meat, spinach, and dry beans. In a recent study,
Chakraborty et al. indicated that iron-deficiency anemia was associated with a
reduction in antioxidant enzymes, and so to an increase in oxidative stress and a
worsening of PD.

-Zinc is the most abundant trace mineral necessary for the body. The primary
source of dietary zinc is protein-rich foods, spinach, nuts, fortified cereals
(Najeeb et al.,2016; Dommisch et al.,2018; Olza et al.,2017). Zinc has
31
antioxidative properties (Najeeb et al.,2016; Dommisch et al.,2018) , starves
reactive oxygen species and neutralizes bacterial toxins (Rostan et al.,2002).
The UK National Health Service recommends that the daily dose for men is 9.5
mg, and 7.0 mg for women (Dommisch et al.,2018) .

-Polyphenols are physiological compounds present in plants. Wine, red fruits,

vegetables, grapes, green tea and coffee are food sources of polyphenols . Most
polyphenols have antioxidative and anti-inflammatory properties (Sliva et
al.,2020).
-Quercetin is a natural plant-derived dietary polyphenol with a high safety
profile and anti-oxidant, anti-inflammatory, and anti-aging effects. The
flavonoid quercetin has been part of the human diet for centuries (Mooney et
al.,2021). It is found in various fruits (e.g., apples, cranberries, and grapes) and
vegetables (e.g., onion, capers, and traditional herbs) (Andres et
al.,2018;Augusco et al.,2023).
-(Zeng et al.2019) demonstrated that quercetin, comparable to chlorhexidine,
effectively reduced biofilm dry weight, total protein content, and the number of
viable cells in Streptococcus mutans biofilms.The anti-inflammatory effect of
quercetin is predominately attributed to its blocking of TNF-α-mediated
inflammation in macrophage cells along with its inhibition of cyclooxygenase
and lipoxygenase (Bureau et al.,2008;Taskan et al.,2020).
- an up-to-date literature review on the nutriments related to periodontal and
chronic diseases was performed. High-sugar, high-saturated fat, low-polyols,
low-fiber and low-polyunsaturated-fat intake causes an increased risk of
periodontal diseases. This pattern of nutrients is classically found in the Western
diet, which is considered as an ‘unhealthy’ diet that causes cardiovascular
diseases, diabetes and cancers. Conversely, low-sugar, high-fiber and high-
omega-6-to-omega-3 fatty acid ratio intake reduces the risk of periodontal
diseases. The Mediterranean, DASH, vegetarian and Okinawa diets that
correspond to these nutritional intakes are considered as ‘healthy’ diets,
reducing this risk of cardiovascular diseases, diabetes and cancers. The role of
micronutrients, such as vitamin D, E, K and magnesium, remains unclear, while
others, such as vitamin A, B, C, calcium, zinc and polyphenols have been
shown to prevent Pods (Chapple et al., 2021;Jeong et al., 2022).

32
b. Smoking cessation
Tobacco smoking, especially in the form of cigarettes, has been convincingly
demonstrated to serve as an important risk factor for periodontitis (Leite et
al.,2018). Tobacco smoke probably exacerbates the pathogenesis of disease
though impacting both the human immuno-inflammatory system and oral
microbial communities. The most common sense approach to reduce this risk is
never to smoke, or to quit smoking. The dentist can play an important role in
encouraging patients not to smoke, or to convince present smokers to quit. The
review by (Kumar,2020) in this volume of Periodontology 2000 expands this
idea to consider prevention of periodontal diseases in individuals engaged in
multiple forms of substance abuse. The point is made that all substances with
abusive potential (such as tobacco, alcohol, and/or narcotics) affect the host
response and the microbiome to influence the pathogenesis of periodontal
diseases. Promotion of tobacco cessation through counselling continues to be an
important tool that dentists need to utilize to help their patients quit smoking. Of
course, the new habit of vaping presents an as-yet mostly unexplored
environmental risk factor that can also negatively impact the periodontium.
- Fullmer et al. (2009) analyzed the subgingival plaque samples from smokers
and quitters and showed that microbial profiles differed significantly between
these two groups at 6- and 12-month intervals after giving up smoking. The
microbial community in smokers was similar to baseline, while quitters
exhibited significantly divergent profiles. At the bacterial species level, smoking
cessation led to a decrease in periodontal pathogens, including Porphyromonas
endodontalis, Dialister pneumosintes, Parvimonas micra, F. alocis, and
Treponema denticola (T. denticola), in association with an increase in the level
of health-associated species Veillonella parvula (Delima et al., 2010). The
beneficial effects of smoking cessation on the periodontium are evident.
Smoking cessation reduces the risks of the onset and progression of periodontal
disease, reduces the risk of tooth loss, and improves the clinical outcomes of
periodontal therapy (Dietrich et al., 2015; Leite et al., 2018).

-smoking stimulates the inflammatory response and impairs protective response,

thus accelerating the periodontal destruction. The changes associated with the
immune response in subgingival environment can also have an impact on the
microbial community. Neutrophils are the primary leukocytes, which are critical
for the defense against bacterial invasion by phagocytosis in human body.
However, both in vitro and in vivo studies have shown that smoking can impair

33
the chemotaxis and phagocytosis of neutrophils in the periodontium (Guntsch et
al., 2006; Zappacosta et al., 2011), leading to defective clearance of bacteria and
thereby increasing the colonization. Furthermore, smoking has been shown to
inversely correlate with the levels of serum immunoglobulin (Ig) G antibodies
specific for some periodontal pathogens (Graswinckel et al., 2004; Tebloeva et
al., 2014). Vlachojannis et al. (2010) assessed the levels of IgG antibody to
multiple periodontal bacteria in a large population of US adults and found that
current smokers were less likely to have higher antibody titers for periodontal
pathogens, such as P. gingivalis, Campylobacter rectus, and Prevotella
nigrescens after adjusting important confounding factors. The reduced level of
IgG antibody can impair the host immune response and exert a “protective”
effect on these periodontal pathogens.

3.4 Management of systemic condition

Control diabetes and other health issues, Among the associations observed
between oral health status and chronic systemic diseases, the link between
periodontal disease and diabetes mellitus is the most consistent.
-Diabetes increases the susceptibility to periodontal disease through various
mechanisms, including impaired neutrophil function, increased collagenase
activity, and changes in the subgingival microbiota (Lalla & Papapanou ,2011)
The high glucose levels in gingival crevicular fluid provide a favorable
environment for pathogenic bacteria that lead to periodontitis. Furthermore, the
inflammatory response is altered in diabetic patients, leading to an increased
production of inflammatory cytokines, which contribute to the tissue destruction
observed in periodontal disease (Preshaw et al.,2012).

-Endocrine diseases such as diabetes and hormonal fluctuations that are

associated with puberty and pregnancy are well-known examples of systemic
conditions that adversely affect the condition of the periodontium. Endocrine
disturbances and hormone fluctuations affect the periodontal tissues directly,
modify the tissue response to local factors, and produce anatomic changes in the
gingiva that may favor plaque accumulation and disease progression
Diabetes mellitus, a major concern in periodontology, is a metabolic disorder
marked by chronic hyperglycemia due to impaired insulin production or action.
It affects glucose, lipid, and protein metabolism, leading to complications like
vascular diseases, infections, and poor wound healing. About 10.5% of the U.S.
population has diabetes, with many cases undiagnosed. Type 1 diabetes, an

34
autoimmune disease mainly affecting children and young adults, requires
insulin therapy and has severe symptoms. Type 2 diabetes, the most common
form, often develops in obese adults due to insulin resistance and can usually be
managed with diet and medication.
-The association between periodontitis and metabolic syndrome is thought to be
the result of systemic oxidative stress and an increased inflammatory response
(Lamster & Pagan,2017).

-Obesity is associated with increased cytokine production as well as T-cell and

monocyte/macrophage dysfunction, factors known to contribute to periodontitis.
The proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor
alpha (TNF-α), which are elevated in obese individuals, are
thought to be produced by activated macrophages that have infiltrated adipose
tissue (Knight et al.,2016).

-In young adults, only programs for pregnant women have prioritized the
diagnosis and prevention of periodontal diseases. One study reported that the
consumption of L. reuteri lozenges may be a useful complement in the control
of pregnancy gingivitis (Schlangenhauf et al.,2016) .

3.5 Regular dental visit

Regular dental check-ups play a crucial role in the prevention and management
of periodontal disease. These visits allow for early diagnosis and timely
intervention, preventing progression from gingivitis to periodontitis (Preshaw et
al., 2018). Professional mechanical plaque removal (PMPR) during routine
check-ups has been shown to significantly reduce inflammation and prevent
clinical attachment loss (Tonetti et al., 2015).

For patients undergoing periodontal therapy, supportive periodontal care (SPC)

at regular intervals (typically every 3–6 months) has been proven to maintain
periodontal health and reduce tooth loss over time (Sanz et al., 2020).
Furthermore, regular dental visits have systemic benefits, as untreated
periodontal disease has been linked to increased risks of diabetes,
cardiovascular disease, and adverse pregnancy outcomes (Hajishengallis, 2015).

35
4. Biological strategies for prevention: probiotic and vaccine
-Probiotics have received considerable attention recently as a potential
approach to prevent periodontal disease. Probiotics are defined by the
Food and Agricultural Organization/World Health Organization as “live
micro-organisms which, when administered in adequate amounts,”
confer a health benefit on the host. A number of mechanisms have been
suggested to explain the benefits associated with probiotic bacteria. The
accompanying review explores the potential mechanisms and clinical
evidence concerning the use of probiotics to prevent periodontal
disease.(Myneni et al.,2020). Probiotic bacteria may reverse damage to
epithelia, caused by inflammation ,through stimulating the upregulation
of structural proteins. These bacteria may also colonize and proliferate
sufficiently to deprive pathogenic bacteria of nutrients and thus inhibit
their growth. Probiotic bacteria have also been reported to produce
antimicrobial products, such as acetic acid and lactic acid, that inhibit
gram-negative bacteria. Moreover, probiotics may influence the host to
downregulate pathways that might damage host tissues, while
simultaneously upregulate other pathways that inhibit the growth or
virulence of pathogens. Lactic acid bacteria(LAB) represent the
prevailing microorganisms employedas probiotics and are categorized
into six distinct groups,namely Lactobacillus, Bifidobacterium,
Enterococcus,Streptococcus, Leuconostoc,
andPediococcus(Tannock,1997)
-Another biological strategy considered to prevent periodontal disease
revolves around the development of a vaccine. Vaccines, “an inactivated
or attenuated pathogen or a component of a pathogen(nucleic acid,
protein) that when administered to the host stimulates a protective
response of cells in the immune system”, have been long in use in
medicine as an effective public health intervention to prevent diseases.
Periodontal vaccines, which have been a subject of research starting in
the 1970s, are a proposed preventive modality for periodontal disease
based on its polymicrobial etiology. A number of research groups have
reported a periodontal vaccine in development which targets antigens of
specific oral gram-negative anaerobic pathogens that have been
implicated in the pathogenesis of this disease.
-A study was done on clinical trial to evaluate the effects of probiotics
and kefir consumption in initial periodontal therapy (IPT) on oral
microbiota composition and treatment outcomes in patients with

36
periodontitis. The study was carried out in the Gazi University
Department of Periodontology, including a sample size of 36 individuals
and utilizing a randomized controlled design. Thirty-six patients with
periodontitis were randomly allocated to three groups: one receiving
probiotic treatment, another receiving kefir, and a third serving as the
control group. Obtaining subgingival microbial samples, we recorded
plaque, gingival index, bleeding on probing, periodontal pocket depth,
and clinical attachment level (periodontal clinical indices) and then
performed IPT. For 14 days, patients took either probiotics, kefir, or no
supplements. Data for the first and third months were collected using
periodontal clinical indices. DNA sequencing was performed to detect
Tannerella forsythia, Porphyromonas gingivalis, and Treponema
denticola in subgingival plaque samples collected at baseline and three
months.Results: Significant differences were observed regarding
periodontal clinical indices among groups in the intragroup comparisons.
Moreover, levels of Tannerella forsythia were significantly decreased in
all groups.The study conclude that Kefir can be administered in addition
to IPT, providing results similar to those observed with probiotics (Cagiar
et al.,2005)
-Recent clinical studies and systematic reviews have demonstrated that
probiotics can improve several periodontal health parameters when used
alongside standard treatments like scaling and root planing (SRP).
According to a meta-analysis by( Invernici et al. (2022), probiotic
supplementation resulted in statistically significant improvements in
periodontal pocket depth (PPD), clinical attachment level (CAL), and
bleeding on probing (BOP). These improvements were observed across
various probiotic strains, especially Lactobacillus reuteri and
Bifidobacterium species.

-In another systematic review,( Khouly et al. (2021) reported that

probiotics led to reductions in pro-inflammatory cytokines such as
interleukin-6 (IL-6) and matrix metalloproteinase-8 (MMP-8), indicating a
modulation of host immune response. Additionally, levels of key
periodontal pathogens, such as Porphyromonas gingivalis, Tannerella
forsythia, and Fusobacterium nucleatum, were significantly reduced
following probiotic use.

37
5.Prevention of peri-implant disease
Like teeth, dental implants can suffer from progressive loss of
supporting tissues as a result of exposure to dental plaque
microorganisms that adhere to the implant surface. Indeed, a
considerable proportion of implants placed will experience peri-
implantitis over their lifespan. While not as well studied as periodontitis,
approaches used to prevent peri-implantitis probably mirror those used
to prevent destruction of the periodontal tissues that support natural
teeth. Wang and colleagues provide an excellent overview on the
prevention of peri-implantitis(Fu &Wang ,2020). They conclude that, like
teeth, dental implants must be cleansed daily, using toothbrushes &
interdental aids, to remove biofilm. In addition, professional mechanical
debridement must be performed at regular intervals (every3 months) to
reduce the submucosal microbial load. It is also suggested that a healthy
lifestyle, including maintenance of good glycemic control and avoiding
smoking, will help ensure long-term retention of implants.

6.Phases of the treatment of periodontal diseases

6.1Phase I or the nonsurgical phase

When successfully performed, this phase controls and stops the progression of
dental and periodontal disease, Phase I periodontal therapy, also called non-
surgical periodontal therapy (NSPT), involves controlling the microbial and
local etiologic factors of periodontal disease to halt progression and promote
healing (Lang et al., 2008). This phase is considered foundational in treating
gingivitis and periodontitis and is essential before any surgical interventions are
planned.
The following list of elements makes up phase I therapy:
1. Patient education and oral hygiene instruction
2. Complete removal of supragingival calculus
3. Correction or replacement of poorly fitting restorations and other
Prosthetic devices.
4. Restoration of carious lesions.
5. Orthodontic tooth movement.
6. Treatment of food impaction areas
7. Treatment of occlusal trauma.

38
8. Extraction of hopeless teeth.
9. Possible use of antimicrobial agents.

Sequence of Procedures
Step 1: Plaque or Biofilm Control Instruction
Plaque or biofilm control is an essential component of successful periodontal
therapy, and instruction should begin at the first treatment appointment. Before
oral hygiene instruction, the patient must understand the reason that he or she
must actively participate in therapy. The explanation of the etiology of the
disease must be presented to the patient. Once the patient understands the nature
of periodontal disease and the etiology, it will be easier to teach the hygiene that
he or she must practice. The patient must be instructedon the correct technique
to remove the plaque or biofilm; this means focusing on applying the bristles at
the gingival third of the clinical crowns, where the tooth meets the gingival
margin. This technique is sometimes referred to as targeted oral hygiene (H.
Takei, Personal communication, 2009) and is synonymous with the Bass
technique. Instructions are also initiated for interdental cleaning aid .

Step 2: Removal of Supragingival and Subgingival Plaque or Biofilm and

Calculus
The initial step involves thorough mechanical debridement to eliminate
dental plaque and calculus deposits above and below the gum line. This
process, known as scaling and root planing (SRP), reduces microbial
load and inflammation, promoting healing of periodontal tissues (Cobb,
2002). Removal of calculus is accomplished using scalers, curettes,
ultrasonic instrumentation, or combinations of these devices during one
or more appointments. In addition to calculus and plaque or biofilm
removal, cementum exposed to the pocket environment should be
removed. At one time it was thought that the removal of all cementum
was necessary to attain a smooth, glassy, hard surface. The rationale
was that cementum became necrotic from penetration of endotoxins
from the microbial biofilm and would interfere with healing. Current
studies have indicated that endotoxins do not penetrate into the
cementum as deeply as once believed and complete removal of the
cementum may not always be necessary, but removal of the plaque or
biofilm and calculus is absolutely necessary.

39
Step 3: Recontouring Defective Restorations and Crowns
Corrections of restorative defects, which are plaque- or biofilm retentive areas,
may be accomplished by smoothing the rough surfaces and removing overhangs
from the faulty restorations with burs or hand instruments, or complete
replacement of the failing restorations may be necessary. All these steps are
important to remove the local risk factors that perpetuate the inflammatory
process, Defective restorations with overhanging margins or improper contours
create plaque-retentive zones, which exacerbate periodontal inflammation. Their
recontouring or replacement is crucial for periodontal health (Lang et al., 2008).

Step 4: Management of Carious Lesions

Removal of the carious lesions and placement of either temporary or permanent
restorations are indicated in phase I therapy because of the infectious nature of
the carious process. Healing of the periodontal tissues is maximized by
removing the reservoir of bacteria in these lesions so that they cannot repopulate
the microbial plaque. Untreated carious lesions harbor bacteria that can worsen
periodontal conditions. Management of caries during this phase ensures the
elimination of infection sources and enhances periodontal therapy outcomes
(Pihlstrom et al., 2005).

Step 5: Tissue Reevaluation

After scaling, root planning, and other phase I procedures, the periodontal
tissues require approximately 4 weeks to heal. This time allows the connective
tissues to heal, and accurate probe depths can be measured. Patients will also
have the opportunity to improve their home care skills to reduce gingival
inflammation and adopt new habits that will ensure the success of treatment. At
the reevaluation appointment, periodontal tissues are probed, and all related
anatomic conditions are carefully evaluated to determine whether further
treatment, including periodontal surgery, is indicated . Approximately 4–6
weeks after Phase I treatment, a reevaluation is performed to assess
tissue response. This includes reassessing pocket depths,
inflammation, and patient compliance, guiding further therapy or
maintenance (American Academy of Periodontology , 2015).

40
Chemotherapy
the causative microorganisms should be identified, and the most effective agent
should be selected with the use of antibiotic-sensitivity testing. Although this
appears simple, the difficulty lies primarily in identifying the specific etiologic
microorganisms rather than the microorganisms that are simply
associated with various periodontal disorders.
-The systemic administration of antibiotics may be a necessary adjunct
for controlling bacterial infection because bacteria can invade periodontal
tissues, thereby making mechanical therapy alone sometimes ineffective.
- Although oral bacteria are susceptible to many antibiotics, no single
antibiotic at the concentrations achieved in body fluids inhibits all putative
periodontal pathogens.
- The protocol for use of antibiotic agents depends on the mechanism of action,
the patient’s health status and history, and the clinical presentation.
A-Systemic antibiotics:
1.Tetracyclines
Tetracyclines have been widely used for the treatment of periodontal diseases.
They have been frequently used to treat refractory periodontitis, including
localized aggressive periodontitis (LAP). These antibiotics are particularly
valuable due to their high concentration in gingival crevicular fluid and their
ability to inhibit matrix metalloproteinases (MMPs), which play a role in tissue
destruction. They also exert anti-inflammatory properties beyond their
antimicrobial effects (Slots, 2004).
As a result of increased resistance to tetracyclines, metronidazole or amoxicillin
in combination with metronidazole has been found to be more effective for the
treatment of aggressive periodontitis in children and young adults.
Side effects
include gastrointestinal disturbances, photosensitivity, hypersensitivity,
increased blood urea nitrogen levels, blood dyscrasias, dizziness, and headache.
In addition, tooth discoloration occurs when this drug is administered to
children who are 12 years old or younger
2.Metronidazole
Metronidazole has been used clinically to treat acute necrotizing ulcerative
gingivitis, chronic periodontitis, and aggressive periodontitis, Effective against

41
anaerobic bacteria like Porphyromonas gingivalis and Prevotella intermedia,
metronidazole is often used alone or in combination with amoxicillin to enhance
its effect against mixed infections (Cobb, 2002).
• Mechanism of Action: It disrupts DNA synthesis in anaerobic bacteria,
leading to cell death.
• Clinical Application: When used in combination with scaling and root
planing, metronidazole has been shown to enhance clinical outcomes in chronic
periodontitis patients (Mombelli et al., 2024)
Side Effects
Metronidazole has an Antabuse effect when alcohol is ingested. The response is
generally proportional to the amount ingested and can result in severe cramps,
nausea, and vomiting. Products that contain alcohol should be avoided during
therapy and for at least 1 day after therapy is discontinued. Metronidazole also
inhibits warfarin metabolism

3-Amoxicillin–Clavulanate Potassium
Amoxicillin with clavulanate (Augmentin) may be useful for the management
of patients with LAP or refractory periodontitis. Bueno and colleagues9
reported that Augmentin arrested alveolar bone loss in patients with periodontal
disease that was refractory to treatment with other antibiotics, including
tetracycline, metronidazole, and clindamycin, It is especially beneficial in
rapidly progressive cases (Heitz-Mayfield & Lang, 2013). This combination
extends the spectrum of amoxicillin by inhibiting beta-lactamase enzymes
produced by resistant bacteria.
• Mechanism of Action: Amoxicillin inhibits bacterial cell wall synthesis, while
clavulanate prevents the degradation of amoxicillin by beta-lactamase enzymes.
• Clinical Application: Studies have indicated that amoxicillin-clavulanate,
when used as an adjunct to mechanical therapy, can lead to significant
improvements in periodontal parameters (Cochrane Database of Systematic
Reviews, 2020)
4-Clindamycin
Clindamycin has demonstrated efficacy in patients with periodontitis that are
refractory to tetracycline therapy, Clindamycin is effective against
Porphyromonas gingivalis and other anaerobes involved in periodontitis and
shows good penetration into periodontal tissues, making it a suitable alternative
in patients allergic to penicillin (Feres et al., 2022)

42
Side effects:
Clindamycin has been associated with pseudomembranous colitis, Diarrhea or
cramping that develops during clindamycin therapy may be indicative of colitis,
and it should be discontinued
5.Ciprofloxacin
. At present, ciprofloxacin is the only antibiotic in periodontal therapy to which
all strains of A. actinomycetemcomitans are susceptible. Ciprofloxacin
demonstrates strong activity against Aggregatibacter actinomycetemcomitans
and enhances neutrophil function. It is particularly beneficial when combined
with mechanical debridement in chronic and aggressive periodontitis
(Matarazzo et al., 2023).
Side Effects Nausea, headache, metallic taste in the mouth, and
abdominal,discomfort

Regimen Dose
Amoxicillin 500 mg Three times daily for 8
days
Ciprofloxacin 500 mg Twice daily for 8 days
Clindamycin 300 mg Three times daily for 10
days
Doxycycline or 100–200 mg Once daily for 21 days
minocycline
Metronidazole 500 mg Three times daily for 8
days
Metronidazole + 250 mg of Three times daily for 8
amoxicillin each days

These regimens are prescribed after a review of the patient’s medical history, periodontal diagnosis, and
antimicrobial testing. Clinicians must consult pharmacology references such as Mosby’s GenRx45 or the
manufacturer’s guidelines for warnings, contraindications, and precautions.
Data from Jorgensen MG, Slots J. Practical antimicrobial periodontal therapy. CompendContin Educ Dent.
2000; 21:1

B. Local Chemotherapeutic Agents

Local drug delivery (LDD) systems offer targeted antimicrobial activity
directly into the periodontal pocket, ensuring high local concentration with
minimal systemic exposure.
• Chlorhexidine Gluconate Chips (PerioChip): These biodegradable chips
release chlorhexidine over 7–10 days and have been shown to significantly

43
reduce probing pocket depth (PPD) when used adjunctively with scaling and
root planing (Heitz-Mayfield & Lang, 2013).
• Doxycycline Hyclate Gel (Atridox): A subgingivally applied gel that hardens
upon contact with crevicular fluid. It provides sustained doxycycline release and
inhibits collagen breakdown by MMPs (Cobb, 2002).

6.2 phase II or surgical therapy

Many moderate to advanced cases cannot be resolved without surgically gaining
access to the root surface for root instrumentation and reducing or eliminating
pocket depth to help the patient remove biofilm. The surgical phase of
periodontal therapy is also referred to as phase II therapy,
Surgical techniques can do the following:
(1) increase access to the root surface, allowing the clinician to remove all
irritants;
(2)reduce or eliminate pocket depth, making it possible for the patient
to maintain the root surfaces free of biofilm.
(3) reshape soft and hard tissues to attain a harmonious topography.
It is used to correct anatomic defects that favor plaque or biofilm accumulation
and pocket recurrence or impair esthetics. The aim of correcting anatomic
problems is to alter defects of the gingival and mucosal tissues that predispose
these areas to disease. Three types of techniques are performed on
noninflamed tissues and in the absence of periodontal pockets:
-Plastic surgery techniques: are used to create or widen the attached keratinized
gingiva by placing soft tissue grafts of various types.
• Esthetic surgery techniques: are used to cover denuded root surfaces resulting
from recession and to re-create lost papillae.
• Preprosthetic techniques: are used to modify the periodontal and neighboring
tissues to receive prosthetic replacements.
Periodontal surgery

Pocket Reduction Surgery

-Resective (e.g., gingivectomy, apically displaced flap, undisplaced flap with or without osseous
resection)
-Regenerative (e.g., flaps with grafts, membranes)

44
 Correction of Anatomic or Morphologic Defects
-Plastic surgery techniques used to widen attached gingiva (e.g., free gingival grafts)
-Esthetic surgery (e.g., root coverage, recreation of gingival papillae)
- Preprosthetic techniques (e.g., crown lengthening, ridge augmentation, vestibular deepening)
- Placement of dental implants, including techniques for site development for implants (e.g.,
guided bone regeneration, sinus grafts)

Surgical Pocket Therapy

Surgical pocket therapy can be used to gain access to the diseased root surface
to ensure the removal of calculus located subgingivally before surgery and to
eliminate or reduce the depth of the periodontal pocket. In moderate to
advanced cases, and in cases with furcation invasion and infrabony defects, it
may be difficult and even impossible to resolve periodontal inflammation
completely with nonsurgical therapy alone. Adjunctive periodontal access
surgery is necessary in many of these cases to treat the periodontal disease
definitively, create anatomies that are maintainable long-term by both the
patient and the clinician. Periodontal access surgery is an adjunct to nonsurgical
periodontal therapy and should occur only once the patient has demonstrated
effective biofilm control. The primary objective of periodontal access surgery is
to obtain access for root instrumentation to remove bacterial biofilm and
calculus on the root surfaces thoroughly. The secondary objective of periodontal
access surgery is pocket reduction via soft and hard tissue resection or
periodontal regeneration to facilitate home care and long-term professional
supportive maintenance. These objectives are achieved by two main modalities
of periodontal access surgery, gingivectomy and periodontal flap surgery. Both
gingivectomy and flap surgery provide access for root instrumentation. Open
flap debridement involves reflecting the gingival tissue to gain direct access to
the root surfaces and alveolar bone. This procedure facilitates the thorough
removal of subgingival calculus, granulation tissue, and bacterial biofilms. It
also allows for the reshaping of osseous defects if necessary. According to
(Trombelli et al. ,2023).
Gingivectomy
The word gingivectomy means “excision of the gingiva.” By removing the
pocket wall, gingivectomy provides visibility and accessibility for complete
calculus removal and thorough root planning. This creates a favorable
environment for gingival healing and restoration of a physiologic gingival
contour. Scalpel gingivectomy remains a standard method for treating drug- or

45
appliance-induced gingival overgrowth and shows good clinical outcomes when
performed with proper patient preparation (Bansal et al., 2024)
Diode lasers have gained popularity in gingivectomy due to their advantages in
reducing intraoperative bleeding and postoperative pain (Rastogi et al., 2023)
Topical 2% hyaluronic acid applied post-gingivectomy in combination with
photobiomodulation therapy promotes superior wound healing outcomes
(Rakhshan et al., 2023) Laser gingivectomy has also proven effective in
achieving esthetic improvements, particularly in correcting gingival zenith
contours. (Anwar et al., 2024)
Gingivectomy may be performed for the following indications:
1. Elimination of suprabony pockets if the pocket wall is fibrous and firm
2. Elimination of gingival enlargements

-The modified Widman flap facilitates root instrumentation. It does not attempt
to reduce the pocket depth, but it does eliminate the pocket lining., which used
only horizontal incisions. This technique offers the possibility of establishing an
intimate postoperative adaptation of healthy collagenous connective tissue to
tooth surfaces, and it provides access for adequate instrumentation of the root
surfaces and immediate closure of the area.

-The papilla preservation flap is used when possible in regenerative and

aesthetic cases to minimize recession and loss of interdental papillae. The distal
terminal molar flap is used for treating pockets and osseous defects on the distal
surface of the terminal maxillary and mandibular molars
Guided Tissue Regeneration
GTR is used for the prevention of epithelial migration along the cemental wall
of the pocket and for maintaining space for clot stabilization. This method is
based on the assumption that periodontal ligament and perivascular cells have
the potential for regeneration of the attachment apparatus of the tooth. GTR
consists of placing barriers of different types (membranes) to cover the bone
and periodontal ligament, thus temporarily separating them from the gingival
epithelium and connective tissue. Excluding the epithelium and the gingival
connective tissue from the root surface during the postsurgical healing phase not
only prevents epithelial migration into the wound but also favors repopulation
of the area by cells from the periodontal ligament and the bone.

46
Guided bone regeneration (GBR) is one of the most widely used alveolar bone
augmentation surgeries owing to its ease of operation and reliable outcomes
(Benic &Hammerle ,2014). In GBR, a barrier membrane is placed above the
bone defect. This isolates fast-growing soft tissue cells, allowing slow-growing
osteoblasts to preferentially occupy the defect and promote bone regeneration
(Gou et al.,2019) Originally, the GBR membrane solely served as a physical
barrier to prevent soft tissue penetration and provide space for osteogenesis
(Dahlin et al.,1988;Retzepi &Donos ,2010). The use of polytetrafluoroethylene
(PTFE) membranes has been tested in controlled clinical studies in mandibular
molar furcations and has shown statistically significant decreases in pocket
depths and improvement in attachment levels after 6 months.
Notably, problems such as membrane exposure, which resulted in no or limited
regeneration and the need for a secondary procedure for surgical removal,
resulted in the development of biodegradable membranes. Today in clinical
practice, most GTR procedures use biodegradable membranes, whereas the
nonresorbable membranes, especially those with titanium reinforcement struts,
are used for regeneration of large inftrabony defects and implant site
development. GTR procedures, when supported with proper postoperative care,
can maintain reduced pocket depths and attachment level gains over extended
periods (Gao et al., 2023).
- A recent randomized controlled trial evaluated the 5-year outcomes of GTR
using two different bone graft materials: frozen radiation-sterilized allogenic
bone graft (FRSABG) and deproteinized bovine bone mineral (DBBM). Both
materials demonstrated significant improvements in clinical attachment level
(CAL), probing pocket depth (PPD), and radiographic defect fill. Notably, the
study found no significant difference between the two groups, suggesting that
both grafts are viable options for GTR procedures.
The aim of this study was to compare the efficacy of the guided tissue
regeneration (GTR) of periodontal infrabony defects using the frozen radiation-
sterilized allogenic bone graft (FRSABG) versus deproteinized bovine bone
mineral (DBBM) 5 years after treatment. The association between patients’
compliance and periodontitis recurrence with 5-year outcomes was also
evaluated. Thirty infrabony defects in 15 stage III/IV periodontitis patients were
randomly allocated to the FRSBAG group (tests) or the DBBM group
(controls). Between 1 and 5 years, one patient was lost to follow-up and one
tooth was extracted due to root fracture. No tooth was extracted for periodontal
reasons. Consequently, 13 teeth in test sites and 14 teeth in control sites were
available for the 5-year analysis. The clinical attachment level gain (CAL-G,

47
primary outcome), probing pocket depth (PPD), radiographic defect depth
(DD), and linear defect fill (LDF) were examined at baseline and 5 years post-
surgically. Both groups showed statistically significant improvements in all
evaluated clinical and radiographic parameters at 5 years, with insignificant
intergroup differences. CAL-Gs were 4.46 ± 2.07 mm in the FRSBAG group,
and 3.86 ± 1.88 mm in the DBBM group (p = 0.5442). In six (43%) patients, we
observed periodontitis recurrence, among whom two (33.33%) participated
regularly in supportive periodontal care (SPC) and the other four (66.7%) did
not take part in SPC. A regression analysis revealed that periodontitis
recurrence was a significant predictor of CAL loss and DD increase. FRSBAG
and DBBM were both equally effective 5 years after the GTR of infrabony
defects. Within the limitations of the present study, its outcomes advocate that
both grafts may be considered as a viable option based on patient preferences
and clinical considerations (Brodzikowska et al.,2023).

Membranes used in Guided tissue regeneration:

EPTFE and dPTFE Membranes: Non-resorbable membranes such as expanded
(ePTFE) and dense polytetrafluoroethylene (dPTFE) are widely used for their
structural integrity, though they require a second surgery for removal(Chen et
al., 2023)

2. Collagen-Based Resorbable Membranes

Collagen membranes, derived from porcine or bovine sources, support tissue
healing and avoid the need for a second surgical intervention(Nasr et al., 2023)
3. Synthetic Polymer Membranes
Polymers such as PLA and PGA offer tunable degradation rates and mechanical
properties suitable for GTR applications (Bashir et al., 2023)
4. Nanofiber and Bioactive Membranes
Electrospun nanofiber membranes mimic the extracellular matrix and are being
enhanced with bioactive molecules to support regeneration. (Yang et al., 2023)
-Periodontal disease is a common complication, and conventional periodontal
surgery can lead to severe bleeding. Different membranes have been used for
periodontal treatment with limitations, such as improper biodegradation, poor
mechanical property, and no effective hemostatic property. Guided tissue

48
regeneration (GTR) membranes favoring periodontal regeneration were
prepared to overcome these shortcomings. The mucilage of the chia seed was
extracted and utilized to prepare the guided tissue regeneration (GTR)
membrane. Lignin having antibacterial properties was used to synthesize lignin-
mediated ZnO nanoparticles (∼Lignin@ZnO) followed by characterization with
analytical techniques like Fourier-transform infrared spectroscopy (FTIR), UV–
visible spectroscopy, and scanning electron microscope (SEM). To fabricate the
GTR membrane, extracted mucilage, Lignin@ZnO, and polyvinyl alcohol
(PVA) were mixed in different ratios to obtain a thin film. The fabricated GTR
membrane was evaluated using a dynamic fatigue analyzer for mechanical
properties. Appropriate degradation rates were approved by degradability
analysis in water for different intervals of time. The fabricated GTR membrane
showed excellent antibacterial properties against Staphylococcus aureus (S.
aureus) and Escherichia coli (E. coli) bacterial species.( Sadasivuni et al.,2022).

- Gingival recession represents a significant concern for patients and a

therapeutic problem for clinicians. Several techniques have been proposed to
achieve root coverage. The purpose of this randomized clinical trial was to
evaluate the effect of a guided tissue regeneration (GTR) procedure in
comparison to connective tissue graft (CTG) in the treatment of gingival
recession defects. Twelve patients, each contributing a pair of Miller Class I or
II buccal gingival recessions, were treated. In each patient one randomly chosen
defect received a poly(lactic acid)-based bioabsorbable membrane, while the
paired defect received a CTG. Clinical recordings included oral hygiene
standards and gingival health, recession depth (RD), recession width (RW),
probing depth (PD), clinical attachment level (CAL), and keratinized tissue
width (KT). Mean RD statistically significantly decreased from 2.5 mm
presurgery to 0.5 mm with GTR (81% root coverage), and from 2.5 mm to 0.1
mm with CTG (96% root coverage), at 6 months postsurgery. Prevalence of
complete root coverage was 58% for the GTR group and 83% for the CTG
group. Mean CAL gain was 2.0 mm for the GTR group and 2.2 mm for the
CTG group. No statistically significant differences between treatment groups
were observed for changes in RD, RW, PD, CAL, and KT. Treatment of human
gingival recession defects by means of either GTR or CTG results in clinically
and statistically significant improvement of the soft tissue conditions of the
defect when pre- and post-treatment measurements were compared. Although
differences between CTG and GTR in mean root coverage and prevalence of

49
complete coverage consistently favored the CTG procedure, the differences in
measurements were not statistically significant.( Tatakis et al.,2000)

Guided Bone Regeneration (GBR)

is mainly used in implantology and oral surgery to augment deficient alveolar
bone, commonly in ridge preservation and pre-implant augmentation (Wang &
Boyapati, 2006). GBR uses membranes to exclude soft tissue infiltration,
allowing osteogenic cells to regenerate bone in the desired site.
From a clinical viewpoint, GBR is suited for both horizontal and vertical ridge
augmentation, though vertical augmentation poses a higher risk of membrane
exposure and may require additional stabilization techniques (Urban et al.,
2019; Safi et al., 2024). Non-resorbable membranes, such as titanium-reinforced
PTFE, are preferred in large or vertical defects due to their space-maintaining
capacity.
Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR) are
both regenerative procedures that utilize barrier membranes to promote selective
tissue growth, but they differ in their clinical objectives and applications. GTR
is primarily used to regenerate periodontal structures—namely cementum,
periodontal ligament, and alveolar bone—around natural teeth affected by
periodontitis (Tatakis et al., 2000). In contrast, GBR is designed to facilitate
new bone growth in edentulous areas, often as a preparatory step for dental
implant placement (Buser et al., 1996).

In GTR, the membrane is positioned to prevent the rapid proliferation of

epithelial cells into the periodontal defect, allowing slower-growing periodontal
ligament and bone cells to repopulate the area (Murphy, 2003). GBR, however,
focuses solely on excluding soft tissue from migrating into bony defects, often
combined with bone graft materials to maintain space and stimulate
osteogenesis (Dahlin et al., 1988). The success of GTR is measured by clinical
attachment level gains and probing depth reductions, while GBR outcomes are
assessed based on the quantity and quality of regenerated bone suitable for
implant placement (Hammerle & Jung, 2003).
Both techniques require careful flap management and membrane stabilization,
but GBR generally involves longer healing times and more rigid space
maintaining techniques due to the need for greater bone volume regeneration
(Rosen et al., 2023)

50
Scaffolds in periodontal regenerative treatment
-Advanced periodontitis results in the damage and loss of hard and soft tissues,
which impairs oral function, aesthetics, and the patient’s overall quality of
life(Gerristsen et al.,2010). Although conventional therapies such as scaling and
root plaining and flap surgery effectively interrupt disease progression, it often
necessitates regenerative interventions to regain the original architecture and
function of periodontal tissues because of limitation in spontaneous
regeneration.(Hughes et al.,2010;Sculeanet al.,2008) This requires newly
formed cementum and alveolar bone bridged by functional periodontal
ligament. Conventional regenerative approaches aim at promoting the growth
and differentiation of tissue-resident progenitor cells into fibroblasts,
cementoblasts, and osteoblasts, while preventing the downgrowth of epithelial
tissues into the periodontal defect. This approach, termed guided tissue
regeneration.
-A conventional regenerative strategy, namely, bone grafting, mainly uses
autogenous bone and various bone substitutes. Autog owing to limitations in the
amount of harvestable bone and the necessity of surgical intervention to donor
sites, the use of allografts and xenografts, which are obtained from a donor of
the same or different species, respectively, have been preferred as alternatives
Nevertheless, they carry the risk of unforeseen infection,disease transmission,
and/or immune rejection.(Eppley et al.,2005)
-alloplastic or synthetic bone substitutes, which are mostly made from
hydroxyapatite, for example, tricalcium phosphate, calcium sulfate, biphasic
calcium phosphate, possess osteoconductivity, but are not of biological origin
and, therefore, do not carry the risk of disease transmission. Bone substitute
materials are delivered to osseous defects, including periodontal defects as
scaffolds, and their osteoconductivity is hypothesized to stimulate endogenous
progenitors to grow and differentiate into mature osteoblasts.(Jimi et al.,2012).
-However, a systematic review has revealed that the outcome of periodontal
therapy solely with bone grafting, that is, without accompanying barrier
membranes, is predominantly ascribed to bone regeneration with an attachment
of long junctional epithelium, but with a lack of newly formed cementum and
periodontal ligament.(Sculean et al.,2015).
-Although conventional approaches to periodontal regeneration predominantly
rely on the regenerative capacity of endogenous cells, the comparatively newer
tissue engineering approach aims to combine exogeneous progenitor cells,

51
biomaterial scaffolds, and bioactive molecules (signals) to address the complex
architecture and function of the periodontal tissues.(Laner &Vacati
,1993;Tollemar et al,.2016) In nature, ECM possesses optimal structural
patterns and bioactivity, which regulate the growth and fate of the residing cells
spatiotemporally. Meanwhile, the concept of biomimetics was brought into the
fabrication of tissue engineered constructs for periodontal regeneration. Despite
a large variance among studies, most of the designing concepts converge in
mimicking the hierarchical organization of the native periodontal tissues,
particularly the ECM, structurally and functionally in an ex vivo setting.(Green
et al.,2016) Scaffolds, therefore, serve as the core of tissue engineered construct
because they offer 3-dimensional (3D) structural support and spatial guidance
for cells. Moreover, their functionality may be further enhanced by
incorporating bioactive molecules, for example, growth factors.
-Generally, 3D scaffolds with high porosity and interconnectivity are preferable
to achieve structural and functional restoration, because the architecture offers a
suitable microenvironment for cell-to-cell interaction and scaffold-to-tissue
integration at the implanted site.15,16 In the early phase of implantation, the
porous structures facilitate blood infiltration to the scaffolds and stabilize the
blood clots, which is considered as a key initiator of tissue repair and
regeneration through enriched vascularization.(Tran ,2021;Li et al.,2016).High
porosity also supports the diffusion of nutrients and gases as well as waste
removal, which improves cellular metabolism and growth.(Jin et al.,2019;Dutta
et al.,2017)
-In nature, the ECM has an amorphous porous structure, acting as a scaffold.
Decellularized ECM products from various origins, including human, porcine,
or bovine dermis, and human amniotic membrane (hAM) are commercially
available and used in clinical practice.(Tavelli et al.,2020)
-Recently, donor sites have been extended to the periodontal ligament itself,
and attempts have been made to produce biomimetic periodontal scaffolds using
decellularized ECM in combination with periodontal progenitor cells.(Farag et
al.,2014;Son et al.,2019)
-Although natural ECM serves as the ideal scaffold in nature, particular
attention has been paid to the generation of biomimetic scaffolds using
polymeric biomaterials. Polymeric biomaterials are categorized based on their
origin: natural and synthetic polymers.
-Natural polymers represented by proteins (eg, collagen, silk) and
polysaccharides (eg, cellulose, alginate, chitosan) are often referred as the first

52
biodegradable biomaterials applied in clinical settings.(Nair
&Laurencin,2007;Filippi et al.,2020).
-They possess inherent bioactive properties that actively interact with cellular
components. natural polymers generally lack mechanical stability, and their
mechanical/biological properties may significantly vary depending on extraction
procedures.
-In contrast, synthetic polymers such as polylactic acid, polycaprolactone
(PCL), and poly(DL-lactide-co-glycolide) present superior mechanical
properties and formability for clinical use in a variety of applications in addition
to decent biocompatibility and biodegradability.
-Unlike natural polymers synthetic polymers are biologically inert, and their
hydrophobic nature may hinder blood infiltration, which potentially prevents the
scaffold from integrating to the implanted site.(Baican et al.,2020)
-To supplement the bioinertness of the synthetic polymers, functionalization
using techniques such as plasma surface activation and the coating/additive of
bioactive molecules are preferably performed.(Kurokawa et al.,2017) These
include ECM proteins (eg, collagen, fibronectin, gelatin),(Camposetal.,2014;Liu
et al.,2016;Carmagnola et al.,2017) growth factors (eg,BMP-2, BMP-7,
fibroblast growth factor-2, and platelet-derived growth factorBB),(Lee et
al.,2014;Rasperini et al 2015) specialized proresolving mediators (eg, resolving
D1),(Van ,2017) and various types of antibiotics and anti-inflammatory
drugs.(Batool et al.,2018;Yar et al.,2016;Faooq et al.,2015).
-In a current clinical practice, an autologous connective tissue graft (CTG) is a
frequent procedure to augment soft tissue. In addition to soft tissue regain, a
histologic evaluation has revealed that CTG leads to the regeneration of
cementum on the dentin surface, which may be bound to newly formed
periodontal ligament, indicating connective tissue exhibits
cementoconductivity.(Goldstein et al.,2001). However, the procedure is
accompanied by a number of complications not only at the recipient site, but at
the donor site such as pain, infection, bleeding, and necrosis.(Aguirre et
al.,2017)
-Acellular dermal matrix (ADM) from human skin is the most common
decellularized ECM scaffold in periodontal treatment.(Tavelli et al.,2020)
-Naturally, the ECM of periodontal origin could be considered to possess the
ideal microenvironment (eg, topography, protein composition for periodontal
regeneration.

53
-In the study, decellularized periodontal ECM was repopulated by PDLCS.
Strikingly, PDLSC that were found near the decellularized cementum layer
selectively expressed cementoblast markers, cementum protein-23 and
osteocalcin, while keeping fibrous network within the decellularized area of
periodontal ligament.
-In the study, mandibular premolars were extracted and processed to
decellularize the residual periodontal tissues on the root surface. The teeth were
then replanted in the surgically expanded extraction socket. Interestingly, there
was no significant difference between the freshly extracted teeth and the
decellularized teeth in root resorption, recovered periodontal ligament area and
new cementum formation. The study also showed rich revascularization in the
decellularized matrix, suggesting that decellularized periodontal ECM was
sufficient to retrieve its hierarchical structure and function by recruiting
endogenous progenitors.
-Nevertheless, the clinical translation of decellularized ECM originated from
periodontal tissues seems challenging although periodontal ligament can be
obtained from deciduous teeth, wisdom teeth, and extracted teeth for
orthodontics treatment and then cryopreserved. The technique requires the
provision of infrastructure, namely, “tooth banks,” and improved cost efficiency
before being manufactured as off-the-shelf products for example, ADM and
hAM.(Zeitlin ,2020)
-Contrary to natural ECM-based approaches, bioengineering techniques may be
used to produce biomimetic periodontal scaffolds in combination with
progenitor cells and/or bioactive molecules.
-Electrospun constructs have been used as a substrate to produce biomimetic
periodontal ECM in combination with progenitor cells PDLC seeded on an
electrospun substrate were able to produce ECM by secreting collagen I,
fibronectin, and rich growth factors, which are found in native periodontal
tissues, such as basic fibroblast growth factor, vascular endothelial growth
factor, and hepatocyte growth factor (Farag ,2017;Jiagn ,2021).
-This allowed for further preclinical assessment of the biomimetic periodontal
ECM in surgically created periodontal fenestration defects in rat, showing that it
significantly promoted the regeneration of periodontal ligament, cementum ,and
alveolar bone in comparison to electrospun PCL scaffolds alone.(Farag et
al.,2018)
-The idea of biomimetic periodontal ECM may be further enhanced by
controlling nanofiber orientation in vivo observation in a periodontal

54
fenestration defect model in rat showed that aligned PCL electrospun nanofibers
loaded by PDLC noticeably regenerated periodontal ligament, which was
perpendicularly oriented to the root surface, whereas randomly aligned
nanofibers resulted in irregular ligament orientation (Yang et al, 2019). This
finding suggests that fiber orientation governs the architecture and function at
the regenerated sites.
-PCL electrospun scaffolds functionalized with ibuprofen selectively suppressed
the proliferation of gingival cells subjected to Porphyromonasgingivalis
lipopolysaccharide.(Battol et al.,2018) In an experimentally induced
periodontitis model, PCL electrospun scaffolds functionalized with ibuprofen
significantly decreased local inflammation and further progression but improved
the clinical attachment level in comparison with the nonfunctionalized
counterpart. Functionalization with antibiotics such as doxycycline
hydrochloride, metronidazole, and tetracycline hydrochloride has been also
suggested to be efficacious against the progression of periodontitis and to
provide better sustainability after implantation(Jin et al.,2016; Ranjabar et
al.,2016). These functionalization techniques do not alter the bulk properties of
the polymeric scaffolds, but may offer additional benefits to periodontal
regenerative therapy.(Ranjabar et al.,2016)
-Multiphasic scaffolds are designed to consist of multiple components layer by
layer, each of which specifically targets their corresponding tissue.
Biphasic scaffolds are often designed to combine bone compartment and peri-
odontal compartment. Vaquette and colleagues (2012) developed double-
layered PCL scaffolds which consisted of a bone compartment produced by 3D
printing and an electrospun periodontal compartment.( Vaquette et al., 2012). -
In this study, osteoblasts in suspension and PDLC in sheet were loaded on their
corresponding components, and then the construct was placed on a dentin block
as the periodontal compartment was in contact with the dentin surface before
subcutaneous transplantation in an immuno- deficiency rat model. The
histologic evaluation noted that a cementum-like tissue was formed on the
dentin surface in which fibrous attachment supported, whereas the expression of
alkaline phosphatase was promoted on the bone compartment side. The
following study further optimized the scaffold design by functionalizing the
bone compartment with calcium phosphates, showing improved bone formation
(Costa et al.,2014).
-Triphasic scaffolds are mostly designed to individually target each of

55
components in periodontal tissues ,Triphasic scaffolds are designed to
regenerate the three key periodontal tissues—cementum, periodontal ligament
(PDL)Lee and colleagues (2014) verified the triphasic concept by the orthodox
tissue engineering approach, namely, by combining scaffolds, bioactive
molecules, and progenitor cells. In this study, triphasic 3D printed scaffolds of
nanohydroxyapatite-containing PCL were designed by changing porous
patterns. Three phases were designed with 100 mm, 600 mm, and 300 mm
microchannels to approach cementum/dentin interface, periodontal ligament,
and alveolar bone, respectively. Subsequently, layers for the cementum–dentin
interface, periodontal ligament, and alveolar bone were functionalized with
human amelogenin, connective tissue growth factor, and BMP-2, respectively,
before the scaffold was loaded by dental pulp stem cells and transplanted
subcutaneously in immunodeficient mice.which successfully guided tissue-
specific regeneration in mice.
-A personalized medicine approach underlies the concept of pathologic
variation among patients(Hamburg &Collins,2010). Optimal periodontal
regeneration requires spatial guidance to progenitor cells with rich
vascularization while preventing epithelial downgrowth.( Ramseier et al .,2012)
-This goal could be achieved by applying a medical imaging system such as a
high-resolution cone beam CT scan in scaffold designing.This goal could be
achieved by applying a medical imaging system such as a high-resolution cone
beam CT scan in scaffold designing. The prototype workflow of custom-
designed 3D scaffolds for periodontal regeneration was introduced by Park and
colleagues49,63 (2010, 2012). Surgically created periodontal fenestration
defects were scanned by a micro-CT scan, and the scanned files were then
transferred into CAD software as 3D image data in .stl format, where the
scaffold geometry was designed to adapt to the defect. In the scaffold,
microchannel architectures were included in the scaffold to provide an
orientational guide to periodontal ligament fibers. Subsequently, a wax mold
was created by a wax printer, and PCL was casted in the mold.(Park et
al.,2010;Park et al.,2012). After the sterilization process, PDLC were loaded on
the custom-designed scaffold and transplanted to the defect site(Park et
al.,2012). After 4 weeks of healing, the custom-designed scaffold resulted in a
significant increase in bone mass and mineral density, and the alignment of
regenerated periodontal ligament was oriented more regularly in comparison
with amorphous scaffolds ,Strikingly, the expression of periostin, which is the
regulator of collagen fibrogenesis found in functional periodontal ligament(Wen
et al.,2012), was evident in the treated site by the custom-designed scaffold, but

56
not by the amorphous scaffold(Park et al.,2012). This highlight the promise of
personalized scaffolds
-High-resolution 3D printing now enables the creation of defect-specific
scaffolds, aligning with existing dental imaging tools for potential clinical
application. However, clinical evidence remains limited, and challenges such as
the need for preclinical validation in relevant animal models, regulatory
compliance, infrastructure, and cost-effectiveness must be addressed. Future
research should focus on optimizing scaffold design and proving the efficacy
and practicality of tissue-engineered solutions in clinical settings.

Periodontal plastic surgery:

Periodontal plastic surgery is defined as the surgical procedures performed to
correct or eliminate anatomic, developmental, or traumatic deformities of the
gingiva or alveolar mucosa. Periodontal plastic surgery includes only the
surgical procedures of mucogingival therapy (correction of relationships
between the gingiva and the oral mucous membrane, with special reference to
three problem areas: attached gingiva, shallow vestibules, and a frenum
interfering with the marginal gingiva).
-An important objective of periodontal plastic surgery is correction of frenal or
muscle attachments that may extend coronal to the mucogingival junction. If
adequate keratinized, attached gingiva exists coronal to the frenum, it may not
be necessary to remove the frenum. A frenum that encroaches on the margin of
the gingiva can interfere with biofilm removal, and the tension on the frenum
tends to open the sulcus. In these cases, surgical removal of the frenum is
indicated.
-Zucchelli & De Sanctis (2020) define PPS as surgical interventions designed to
improve aesthetics and function of the soft tissue architecture around teeth and
implants, particularly in the esthetic zone.
-Cortellini & Tonetti (2021) describe periodontal plastic surgery as
encompassing a broad set of techniques aimed at correcting soft tissue defects to
restore both aesthetics and periodontal health.
- Muratore & Serino (2023) emphasize that PPS procedures are not merely
cosmetic but serve essential roles in maintaining peri-implant and periodontal
tissue stability.

57
These procedures aim to:
• Achieve root coverage in cases of gingival recession.
• Improve or increase keratinized gingiva and soft tissue thickness.
• Enhance soft tissue contours around teeth and implants.
• Correct mucogingival defects for better aesthetics and oral hygiene
maintenance

Aesthetic crown lengthening

In aesthetic crown lengthening, only a facial flap is raised to prevent loss of
papillary fill. Initial gross osteoplasty is accomplished with a round bur to
reduce excessive bone thickness, followed by alteration of the crestal level with
hand chisels and curettes. It is important to reduce the osseous crest
so that the new position parallels the CEJ at each tooth facially and proximally.
However, the height of the interdental crest is not reduced in aesthetic crown
lengthening. If full exposure of the anatomic crown is desired, the alveolar crest
should be reduced to a position 3 mm apical to the CEJ. Excessive
bone thickness interdentally is reduced with a round bur to produce a slight
prominence of the roots relative to the alveolar ridge. Care should be exercised
to maintain adequate bone thickness over the root surfaces. Creation of an ideal
osseous form leads to predictable and stable soft tissue position and ideal
crown exposure Flap closure is accomplished with interrupted 7-0 sutures.
Postoperative instructions are focused on biofilm control to prevent soft tissue
rebound . Aesthetic crown lengthening is a periodontal surgical procedure
designed to increase the visible portion of the tooth crown by recontouring the
gingival and/or osseous tissue, primarily in the esthetic zone. It is commonly
performed to correct a “gummy smile,” improve gingival symmetry, or expose
sufficient tooth structure for restorative or prosthetic work (Tatakis & Lee,
2021; Deas et al., 2020).

6.3 Suppurative phase of periodontal therapy

Studies indicate that even with appropriate periodontal therapy, some
progression of disease is possible.(Costa et al,2011). One likely

58
explanation for the recurrence of periodontal disease is incomplete
subgingival plaque/biofilm and calculus removal. If subgingival biofilm is left
behind during scaling, it regrows within the pocket. Both the mechanical
debridement performed by the therapist and the motivational environment
provided by the appointment seem to be necessary for good maintenance results
Periodic recall visits form the foundation of a meaningful long-term
prevention program. The interval between visits is usually set at 3 months but
may vary according to the patient’s needs.(Armitage et al.,2016)

Maintenance Recall Procedures

Part I: Examination
(Approximate time: 14 min)
Patient greeting
Medical history changes
Oral pathologic examination
Oral hygiene status
Gingival changes
Pocket depth changes
Mobility changes
Occlusal changes
Dental caries
Restorative, prosthetic, and implant status
Part II: Treatment
(Approximate time: 36 min)
Oral hygiene reinforcement
Scaling
Polishing
Chemical irrigation or site-specific antimicrobial placement
Part III: Report, Cleanup, and Scheduling
(Approximate time: 10 min)
Write report in chart.
Discuss report with patient.
Clean and disinfect operatory.
Schedule next recall visit.
Schedule further periodontal treatment.
Schedule or refer for restorative or prosthetic treatment.

59
Examination and Evaluation
The recall examination is similar to the initial evaluation of the patient
.However, because the patient is not new to the office, the dentist or hygienist
primarily looks for changes that have occurred since the last evaluation.
Radiographic examination must be individualized ,( American Dental
Association Website ,2021) depending on the initial severity of the case and the
findings during the recall visit.
Treatment
Following consultation, examination, and oral hygiene instruction,the required
scaling and root planning are performed . Care must be taken not to instrument
healthy sites with shallow sulci (1- to 3-mm deep) and an absence of gingival
inflammation because studies have indicated that repeated subgingival scaling
and root planning of sites not periodontally involved result in significant loss of
attachment and gingival recession, which will affect esthetics(Lindhe et
al.,1982).
The long-term preservation of the dentition is closely associated with the
frequency and quality of recall maintenance. The therapist should use risk
assessment and educate the patient on the need for periodontal maintenance.
Supportive periodontal therapy is a lifetime effort to prevent the disease from
recurring. Patients who do not return for supportive periodontal therapy lose
more teeth than compliant patients.
-Like teeth, dental implants can suffer from progressive loss of supporting
tissues as a result of exposure to dental plaque microorganisms that adhere to
the implant surface. Indeed, a considerable proportion of implants placed will
experience peri-implantitis over their lifespan. While not as well studied as
periodontitis, approaches used to prevent peri-implantitis probably mirror those
used to prevent destruction of the periodontal tissues that support natural teeth.
Wang and colleagues provide an excellent overview on the prevention of peri-
implantitis (Fu &Wang ,2020). They conclude that, like teeth ,dental implants
must be cleansed daily, using toothbrushes & interdental aids, to remove
biofilm. In addition, professional mechanical debridement must be performed at
regular intervals (every3 months) to reduce the submucosal microbial load. It is
also suggested that a healthy lifestyle ,including maintenance of good glycemic
control and avoiding smoking, will help ensure long-term retention of implants.

60
7.Conclusion
Periodontal disease is a preventable and treatable inflammatory condition
affecting the gums and supporting structures of the teeth. Effective prevention
relies on consistent oral hygiene practices, including daily brushing, flossing,
and regular dental check-ups. Risk factors such as smoking, diabetes, and poor
diet should also be managed to reduce susceptibility. Early detection and
intervention are critical to preventing disease progression. Treatment typically
involves professional cleaning (scaling and root planing), improved home care,
and in advanced cases, surgical procedures. With proper preventive measures
and timely treatment, the progression of periodontal disease can be halted and
oral health significantly improved.

8.Refrences
A
•Adler, C.J., Dobney, K., Weyrich, L.S., Kaidonis, J., Walker, A.W., Haak, W.,
Bradshaw, C.J.A., Townsend, G., Sołtysiak, A., Alt, K.W. and others, 2013.
Sequencing ancient calcified dental plaque shows changes in oral microbiota
with dietary shifts of the Neolithic and Industrial Revolutions. Nature Genetics,
45, pp.450–455.
•Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws,
American Association of Oral and Maxillofacial Surgeons, 2007. American
Association of Oral and Maxillofacial Surgeons position paper on
bisphosphonate-related osteonecrosis of the jaws. Journal of Oral and
Maxillofacial Surgery, 65, pp.369–376.
•Aguirre-Zorzano, L.-A., García-De La Fuente, A.M., Estefanía-Fresco, R., et
al., n.d. [Details missing – please provide full citation information for accurate
formatting.]
•Alshareef, A., Attia, A., Almalki, M., Alsharif, F., Melibari, A., Mirdad, B., et
al., 2020. Effectiveness of probiotic lozenges in periodontal management of
chronic periodontitis patients: Clinical and immunological study. European
Journal of Dentistry, 14, pp.281–287.
•American Academy of Periodontology, 2015. Comprehensive periodontal
therapy: A statement by the American Academy of Periodontology. Journal of
Periodontology, 86(7), pp.835–838.

61
•American Dental Association. (2021). Guide to patient selection and limiting
radiation exposure. [online] Available at:
https://www.ada.org/en/membercenter/oral-health-topics/x-rays [Accessed 10
Sep. 2021].
•Andres, S., Pevny, S., Ziegenhagen, R., Bakhiya, N., Schafer, B., Hirsch-Ernst,
K.I. and Lampen, A., 2018. Safety aspects of the use of quercetin as a dietary
supplement. Molecular Nutrition & Food Research, 62, p.1700447.
•Anonymous. (2002). Evidence supporting zinc as an important antioxidant for
skin. International Journal of Dermatology, 41, pp.606–611.
•Armitage, G.C. and Xenoudi, P., 2016. Post-treatment supportive care for the
natural dentition and dental implants. Periodontology 2000, 71, pp.164–184.
•Arunachalam, L.T., Sudhakar, U., Vasanth, J., Khumukchum, S. and Selvam,
V.V., 2017. Comparison of anti-plaque and anti-gingivitis effect of curcumin
and chlorhexidine mouth rinse in the treatment of gingivitis: A clinical and
biochemical study. Journal of Indian Society of Periodontology, 21, pp.478–
483.
•Augusco, M.A.C., Sarri, D.A., Panontin, J.F., Rodrigues, M.A.M., Fernandes,
R.M.N., Silva, J., Cardoso, C.A.L., Rambo, M.K.D. and Scapin, E., 2023.
Extracts from the leaf of Couroupita guianensis (Aubl.): Phytochemical,
toxicological analysis and evaluation of antioxidant and antimicrobial activities
against oral microorganisms. Plants, 12, p.2327.
B
•Barbosa, A.A., Leite, C.C., Costa, F.H.S. and Almeida, R.C., 2021.
Effectiveness of Lippia sidoides-based products in oral care: A systematic
review. Phytotherapy Research, 35(10), pp.5432–5440.
•Batool, F., Morand, D.-N., Thomas, L., et al., 2018. Synthesis of a novel
electrospun polycaprolactone scaffold functionalized with ibuprofen for
periodontal regeneration: An in vitro and in vivo study. Materials (Basel), 11,
p.580.
•Benic, G.I. and Hammerle, C.H., 2014. Horizontal bone augmentation by
means of guided bone regeneration. Periodontology 2000, 66, pp.13–40.
•Bosma-den Boer, M.M., Van Wetten, M.-L. and Pruimboom, L., 2012.
Chronic inflammatory diseases are stimulated by current lifestyle: How diet,
stress levels and medication prevent our body from recovering. Nutrition &
Metabolism, 9, p.32.

62
•Botelho, M.A., Nogueira, N.A.P., Bastos, G.M., Fonseca, S.G., Lemos, T.L.G.,
Matos, F.J.A. and Montenegro, D., 2008. Antimicrobial activity of the essential
oil from Lippia sidoides, carvacrol and thymol against oral pathogens. Brazilian
Journal of Medical and Biological Research, 41(2), pp.101–107.
•Brodzikowska, A., Górski, B., Szerszeń, M. and Sanz, M., 2023. Efficacy of
guided tissue regeneration using frozen radiation-sterilized allogenic bone graft
as bone replacement graft compared with deproteinized bovine bone mineral in
the treatment of periodontal intra-bony defects: Randomized controlled trial.
Journal of Clinical Medicine, 12(4), p.1396.
•Bureau, G., Longpre, F. and Martinoli, M.G., 2008. Resveratrol and quercetin,
two natural polyphenols, reduce apoptotic neuronal cell death induced by
neuroinflammation. Journal of Neuroscience Research, 86, pp.403–410.
•Buser, D., Dula, K., Belser, U.C., Hirt, H.P. and Berthold, H., 1996. Localized
ridge augmentation using guided bone regeneration. Clinical Oral Implants
Research, 7(3), pp.211–220.
C
•Caglar, E., Kargul, B. and Tanboga, I., 2005. Bacteriotherapy and probiotics’
role on oral health. Oral Diseases, 11(3), pp.131–137.
•Carmagnola, D., Tarce, M., Dellavia, C. et al., 2017. Engineered scaffolds and
cell-based therapy for periodontal regeneration. Journal of Applied Biomaterials
& Functional Materials, 15, pp.e303–e312.
•Cekici, A., Kantarci, A., Hasturk, H. and Van Dyke, T.E., 2014. Inflammatory
and immune pathways in the pathogenesis of periodontal disease.
Periodontology 2000, 64(1), pp.57–80.
•Chapple, I.L.C., 2009. Potential mechanisms underpinning the nutritional
modulation of periodontal inflammation. Journal of the American Dental
Association, 140(2), pp.178–184.
•Chapple, I.L.C., 2022. Time to take gum disease seriously. British Dental
Journal, 232(6), pp.360–361.
•Chapple, I.L.C., Bouchard, P., Cagetti, M.G., Campus, G., Carra, M.C., Cocco,
F. et al., 2021. Nutrition and periodontal health: Consensus report of the
European Federation of Periodontology and the International Association for
Dental Research. Journal of Clinical Medicine, 10(2), p.197.

63
•Ciancio, S.G., 1983. Use of antibiotics in periodontal therapy. In: M.G.
Newman and A. Goodman, eds. Antibiotics in Dentistry. Chicago:
Quintessence, pp
•Cobb, C.M., 2002. Clinical significance of non-surgical periodontal therapy:
An evidence-based perspective of scaling and root planing. Journal of Clinical
Periodontology, 29(s2), pp.6–16. https://doi.org/10.1034/j.1600-051X.29.s2.4.x
•Costa, P.F., Vaquette, C., Zhang, Q. et al., 2014. Advanced tissue engineering
scaffold design for regeneration of the complex hierarchical periodontal
structure. Journal of Clinical Periodontology, 41(3), pp.283–294.
D
•Dahlin, C., Linde, A., Gottlow, J. and Nyman, S., 1988. Healing of bone
defects by guided tissue regeneration. Plastic and Reconstructive Surgery,
81(5), pp.672–676.
•Dahlin, C., Linde, A., Gottlow, J. and Nyman, S., 1988. Healing of bone
defects by guided tissue regeneration. Plastic and Reconstructive Surgery,
81(5), pp.672–676. https://doi.org/10.1097/00006534-198805000-00004
•Davies, A., 1973. The mode of action of chlorhexidine. Journal of Periodontal
Research, 12(Suppl.), pp.68–75.
•Deas, D.E., Moritz, A.J., McDonnell, H.T. and Powell, C.A., 2020. Crown
lengthening: a periodontal perspective. Compendium of Continuing Education
in Dentistry, 41(3), pp.168–174.
•Dommisch, H., Kuzmanova, D., Jönsson, D., Grant, M. and Chapple, I.L.C.,
2018. Effect of micronutrient malnutrition on periodontal disease and
periodontal therapy. Periodontology 2000, 78(1), pp.129–153.
E
•European Food Safety Authority (EFSA). (2015). Scientific opinion on dietary
reference values for vitamin A. EFSA Journal, 13(3), p.4028.
https://doi.org/10.2903/j.efsa.2015.4028
F
•Farag, A., Hashimi, S.M., Vaquette, C., et al. (2018). The effect of
decellularized tissue engineered constructs on periodontal regeneration. Journal
of Clinical Periodontology, 45, pp.586–596.
•Farag, A., Vaquette, C., Theodoropoulos, C., et al. (2014). Decellularized
periodontal ligament cell sheets with recellularization potential. Journal of
Dental Research, 93, pp.1313–1319.
64
•Farooq, A., Yar, M., Khan, A.S., et al. (2015). Synthesis of piroxicam-loaded
novel electrospun biodegradable nanocomposite scaffolds for periodontal
regeneration. Materials Science and Engineering: C, 56, pp.104–113.
•Feres, M., Figueiredo, L.C. and Soares, G.M.S. (2022). Antibiotics in the
treatment of periodontitis: Current status and future directions. Periodontology
2000, 89(1), pp.160–173.
•Feres, M., Figueiredo, L.C., Vieira, A.R. and Botelho, M.A. (2013). Clinical
and microbiological evaluation of a herbal gel containing Lippia sidoides in the
treatment of gingivitis. Journal of Applied Oral Science, 21(2), pp.151–156.
•Fernández, C.E., Maturana, C.A., Coloma, S.I., Carrasco-Labra, A. and
Giacaman, R.A. (2021). Teledentistry and mHealth for promotion and
prevention of oral health: A systematic review and meta-analysis. Journal of
Dental Research, 100(9), pp.914–927.
•Finney, M., Walker, J.T., Marsh, P.D. and Brading, M.G. (2003).
Antimicrobial effects of a novel Triclosan/zinc citrate dentifrice against mixed
culture oral biofilms. International Dental Journal, 53(Suppl. S1), pp.371–378.
•Forouhi, N.G., Krauss, R.M., Taubes, G. and Willett, W. (2018). Dietary fat
and cardiometabolic health: Evidence, controversies, and consensus for
guidance. BMJ, 361, p.k2139.
•Fu, J.H. and Wang, H. (2020). Breaking the wave of peri-implantitis.
Periodontology 2000, 84(1), pp.161–175.
•Fujii, H., Iwase, M., Ohkuma, T., et al. (2013). Impact of dietary fiber intake
on glycemic control, cardiovascular risk factors and chronic kidney disease in
Japanese patients with type 2 diabetes mellitus: The Fukuoka Diabetes Registry.
Nutrition Journal, 12, p.159.

G
• Gao, X., Zhang, Y. and Li, Y. (2023). Long-term outcomes of guided
tissue regeneration in periodontal therapy: A systematic review and meta-
analysis. Journal of Periodontology, 94(3), pp.349–359.
• Genco, R.J. and Borgnakke, W.S. (2013). Risk factors for periodontal
disease. Periodontology 2000, 62, pp.59–94.

65
• Goldstein, M., Boyan, B.D., Cochran, D.L., et al. (2001). Human
histology of new attachment after root coverage using subepithelial connective
tissue graft. Journal of Clinical Periodontology, 28, pp.657–662.
• Gómez, M.V., Toledo, A., Carvajal, P., et al. (2018). A multicenter study
of oral health behavior among adult subjects from three South American cities.
Brazilian Oral Research, 32, e22.
• Gondivkar, S.M., Gadbail, A.R., Gondivkar, R.S., et al. (2019). Nutrition
and oral health. Disease-a-Month, 65, pp.147–154.
• Gou, M., Huang, Y.Z., Hu, J.G., et al. (2019). Epigallocatechin-3-gallate
cross-linked small intestinal submucosa for guided bone regeneration. ACS
Biomaterials Science & Engineering, 5, pp.5024–5035.
• Gröber, U., Reichrath, J., Holick, M.F. and Kisters, K. (2014). Vitamin
K: An old vitamin in a new perspective. Dermato-Endocrinology, 6, e968490.
H
• Hajishengallis, G. (2015). Periodontitis: From microbial immune
subversion to systemic inflammation. Nature Reviews Immunology, 15(1),
pp.30–44. https://doi.org/10.1038/nri378
• Hajishengallis, G. (2020). Interconnection of periodontal disease and
comorbidities via inflammation. Nature Reviews Immunology, 20(1), pp.40–55.
https://doi.org/10.1038/s41577-019-0178-8
• Hamburg, M.A. and Collins, F.S. (2010). The path to personalized
medicine. New England Journal of Medicine, 301, pp.1–4.
• Hämmerle, C.H.F. and Jung, R.E., 2003. Bone augmentation by means of
barrier membranes. Periodontology 2000, 33, pp.36–53.
• Haps, S., Slot, D.E., Berchier, C.E. and Van der Weijden, G.A. (2008).
The effect of cetylpyridinium chloride-containing mouth rinses as adjuncts to
toothbrushing on plaque and parameters of gingival inflammation: A systematic
review. International Journal of Dental Hygiene, 6, pp.290–303.
• Haydari, M., Bardakci, A.G., Koldsland, O.C., Aass, A.M., Sandvik, L.
and Preus, H.R. (2017). Comparing the effect of 0.06%-, 0.12% and 0.2%
chlorhexidine on plaque, bleeding and side effects in an experimental gingivitis
model: A parallel group, double masked randomized clinical trial. BMC Oral
Health, 17, p.118.
• Heitz-Mayfield, L.J.A. and Lang, N.P. (2013). Surgical and non-surgical
periodontal therapy. Journal of Clinical Periodontology, 40(s14), pp.S58–S66.

66
 I
• Invernici, M.M., Salvador, S.L., Silva, P.H.F., Soares, M.S.M., Casarin,
R.C.V. and Palioto, D.B. (2022). Clinical and microbiological effects of
probiotics as adjuncts to periodontal treatment: A systematic review and meta-
analysis. Nutrients, 14(5), p.1036. https://www.mdpi.com/2072-6643/14/5/1036
• Irving, M., Stewart, R., Spallek, H. and Blinkhorn, A. (2018). Using
teledentistry in clinical practice as an enabler to improve access to clinical care:
A qualitative systematic review. Journal of Telemedicine and Telecare, 24(3),
pp.129–146. https://doi.org/10.1177/1357633X16686776
• Isbrucker, R.A. and Burdock, G.A. (2006). Risk and safety assessment on
the consumption of licorice root (Glycyrrhiza sp. , its extract and powder as a
food ingredient, with emphasis on the pharmacology and toxicology of
glycyrrhizin. Regulatory Toxicology and Pharmacology, 46, pp.167–192.
J
• Jafer, M., Patil, S., Hosmani, J., Bhandi, S.H., Chalisserry, E.P. and Anil,
S. (2016). Chemical plaque control strategies in the prevention of biofilm-
associated oral diseases. Journal of Contemporary Dental Practice, 17, pp.337–
343.
• Jeong, Y., Jung, S. and Kim, J. (2022). Associations of dietary patterns
with the risk of periodontal disease: A systematic review and meta-analysis.
Nutrients, 14(20), p.4362. https://www.mdpi.com/2072-6643/14/20/4362
• Jepsen, S., Caton, J.G., Albandar, J.M., Bissada, N.F., Bouchard, P.,
Cortellini, P., … and Papapanou, P.N. (2018). Periodontal manifestations of
systemic diseases and developmental and acquired conditions: Consensus report
of workgroup 3 of the 2017 World Workshop. Journal of Clinical
Periodontology, 45(Suppl 20), pp.S219–S229.
• Jia, L., Zhang, X., Xu, H., et al. (2016). Development of a doxycycline
hydrochloride-loaded electrospun nanofibrous membrane for GTR/GBR
applications. Journal of Nanomaterials, 2016, pp.1–10.
• Jiang, Y., Liu, J.M., Huang, J.P., et al. (2021). Regeneration potential of
decellularized periodontal ligament cell sheets combined with 15-deoxy-12,14-
prostaglandin J2 nanoparticles in a rat periodontal defect. Biomedical Materials,
16, p.045008.
K

67
• Karamani, I., Kalimeri, E., Seremidi, K., Gkourtsogianni, S. and Kloukos,
D. (2022). Chlorhexidine mouthwash for gingivitis control in orthodontic
patients: A systematic review and meta-analysis. Oral Health & Preventive
Dentistry, 20(1), pp.279–294. https://doi.org/10.3290/j.ohpd.b3170043
• Khouly, I., Braun, R.S. and Mangano, F.G. (2021). Probiotics as an
adjunctive therapy for periodontitis: A systematic review and meta-analysis.
Journal of Periodontology, 92(1), pp.1–14.
• Kinane, D.F., Stathopoulou, P.G. and Papapanou, P.N. (2017).
Periodontal diseases. Nature Reviews Disease Primers, 3, 17038.
• Kirchhof, G., Lindner, J.F., Achenbach, S., Berger, K., Blankenberg, S.,
Fangerau, H. et al. (2018). Stratified prevention: Opportunities and limitations.
Report on the 1st interdisciplinary cardiovascular workshop in Augsburg.
Clinical Research in Cardiology, 107(3), pp.193–200.
https://doi.org/10.1007/s00392-017-1186-y
• Knight, E.T., Liu, J., Seymour, G.J., et al. (2016). Risk factors that may
modify the innate and adaptive immune responses in periodontal diseases.
Periodontology 2000, 71(1), pp.22–51.
• Kumar, P. (2020). Interventions to prevent periodontal disease in tobacco,
alcohol and drug dependent individuals. Periodontology 2000, 84(1), pp.84–
101.
L
• Lalla, E. and Papapanou, P.N. (2011). Diabetes mellitus and
periodontitis: A tale of two common interrelated diseases. Nature Reviews
Endocrinology, 7(12), pp.738–748.
• Lamont, R.J., Koo, H. and Hajishengallis, G. (2023). The oral microbiota:
Community structure and role in health and disease. Microbiology and
Molecular Biology Reviews, 87(1), e00112-22.
• Lamster, I.B. and Pagan, M. (2017). Periodontal disease and the
metabolic syndrome. International Dental Journal, 67(2), pp.67–77.
• Lang, N.P., Bartold, P.M., Cullinan, M., Jeffcoat, M., Mombelli, A.,
Murakami, S. et al. (2008). Consensus report: Aggressive periodontitis. Annals
of Periodontology, 13(1), pp.13–19. https://doi.org/10.1902/jop.2008.080516
• Lasserre, J.F., Leprince, J.G., Toma, S. and Brecx, M.C. (2015).
Electrical enhancement of chlorhexidine efficacy against the periodontal

68
pathogen Porphyromonas gingivalis within a biofilm. New Microbiologica, 38,
pp.511–519.
• Lee, C.H., Hajibandeh, J., Suzuki, T., et al. (2014). Three-dimensional
printed multiphase scaffolds for regeneration of periodontium complex. Tissue
Engineering Part A, 20(9-10), pp.1342–1351.
• Lee, J.E., Lee, J.M., Lee, Y., Park, J.W., Suh, J.Y., Um, H.S. and Kim,
Y.G. (2017). The antiplaque and bleeding control effects of a cetylpyridinium
chloride and tranexamic acid mouth rinse in patients with gingivitis. Journal of
Periodontal & Implant Science, 47(3), pp.134–142.
• Leite, F.R.M., Nascimento, G.G., Scheutz, F. and López, R. (2018).
Effect of smoking on periodontitis: A systematic review and meta-regression.
American Journal of Preventive Medicine, 54(6), pp.831–841.
• Li, J.Y., Cao, H.Y., Liu, P., Cheng, G.H. and Sun, M.Y. (2014).
Glycyrrhizic acid in the treatment of liver diseases: Literature review. BioMed
Research International, 2014, Article ID 872139.
• Lindhe, J., Nyman, S. and Karring, T. (1982). Scaling and root planing in
shallow pockets. Journal of Clinical Periodontology, 9(5), pp.415–426.
M
• Marçal, F.F., Paulo, J.P.M., Barreto, L.G., Guerra, L.M.C. and Silva, P.G.
(2022). Effectiveness of orthodontic toothbrush versus conventional toothbrush
on plaque and gingival index reduction: a systematic review and meta-analysis.
International Journal of Dental Hygiene, 20(1), pp.87–99.
https://doi.org/10.1111/idh.12511
• Matarazzo, F., de Oliveira, F.B. and Mayer, M.P.A. (2023). Systemic
antibiotics in the treatment of periodontitis: A critical review. Journal of
Clinical Periodontology, 50(1), pp.10–22.
• Messier, C., Epifano, F., Genovese, S. and Grenier, D. (2012). Licorice
and its potential beneficial effects in common oro-dental diseases. Oral
Diseases, 18(1), pp.32–39.
• Milward, M.R. and Chapple, I. (2013). The role of diet in periodontal
disease. Clinical Dental Health, 52, pp.18–21.
• Mira, A., Simon-Soro, A. and Curtis, M.A. (2017). Role of microbial
communities in the pathogenesis of periodontal diseases and caries. Journal of
Clinical Periodontology, 44(Suppl 18), pp.S23–S38.

69
• Mooney, E.C., Holden, S.E., Xia, X.J., Li, Y., Jiang, M., Banson, C.N.,
Zhu, B. and Sahingur, S.E. (2021). Quercetin preserves oral cavity health by
mitigating inflammation and microbial dysbiosis. Frontiers in Immunology, 12,
774273.
• Muniz, F.W.M.G., Nogueira, S.B., Cavagni, J. and Rösing, C.K. (2020).
The effect of vitamin C on periodontal treatment: A systematic review. Clinical
Oral Investigations, 24(1), pp.25–34.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780401/
• Murphy, K.G., 2003. Postoperative healing complications associated with
periodontal plastic surgery procedures. Annals of Periodontology, 8(1), pp.266–
275.
• Myneni, S.R.V. and Wang, H.H. (2020). Biological strategies for the
prevention of periodontal disease: Probiotics and vaccines. Periodontology
2000, 84(1), pp.161–175.
N
• Najeeb, S., Zafar, M.S., Khurshid, Z., Zohaib, S. and Almas, K. (2016).
The role of nutrition in periodontal health: An update. Nutrients, 8(9), p.530.
O
• Offenbacher, S., Braswell, L., Loos, A. et al. (1987). Effects of
flurbiprofen on the progression of periodontitis in Macaca mulatta. Journal of
Periodontal Research, 22, pp.473–478.
P
• Papapanou, P.N., Sanz, M., Buduneli, N., Dietrich, T., Feres, M., Fine,
D.H., et al. (2018). Periodontitis: Consensus report of workgroup 2 of the 2017
World Workshop on the Classification of Periodontal and Peri‐Implant Diseases
and Conditions. Journal of Clinical Periodontology, 45(Suppl 20), pp.S162–
S170.
• Park, C.H., Rios, H.F., Jin, Q., et al. (2010). Biomimetic hybrid scaffolds
for engineering human tooth-ligament interfaces. Biomaterials, 31(19),
pp.5945–5952.
• Park, C.H., Rios, H.F., Jin, Q., et al. (2012). Tissue engineering bone-
ligament complexes using fiber-guiding scaffolds. Biomaterials, 33(1), pp.137–
145.
• Phan, T.N., Buckner, T., Sheng, J., Baldeck, J.D. and Marquis, R.E.
(2004). Physiologic actions of zinc related to inhibition of acid and alkali

70
production by oral streptococci in suspensions and biofilms. Oral Microbiology
and Immunology, 19(1), pp.31–38.
• Pihlstrom, B.L., Michalowicz, B.S. and Johnson, N.W. (2005).
Periodontal diseases. The Lancet, 366(9499), pp.1809–1820.
https://doi.org/10.1016/S0140-6736(05)67728-8
• Preshaw, P.M., Alba, A.L., Herrera, D., Jepsen, S., Konstantinidis, A.,
Makrilakis, K. et al. (2012). Periodontitis and diabetes: A two-way relationship.
Diabetologia, 55(1), pp.21–31.
• Preshaw, P.M., Alba, A.L., Herrera, D., Jepsen, S., Konstantinidis, A.,
Makrilakis, K. and Taylor, R. (2018). Periodontitis and diabetes: A two-way
relationship. Diabetologia, 61(1), pp.21–31.
R
• Ramseier, C.A., Rasperini, G., Batia, S. et al. (2012). Advanced
reconstructive technologies for periodontal tissue repair. Periodontology 2000,
59(1), pp.185–202.
• Ranjbar-Mohammadi, M., Zamani, M., Prabhakaran, M.P. et al. (2016).
Electrospinning of PLGA/gum tragacanth nanofibers containing tetracycline
hydrochloride for periodontal regeneration. Materials Science and Engineering:
C, 58, pp.521–531.
• Rasperini, G., Pilipchuk, S.P., Flanagan, C.L. et al. (2015). 3D-printed
bioresorbable scaffold for periodontal repair. Journal of Dental Research,
94(Supplement 1), pp.153S–157S.
• Ravindran, P. (2006). Turmeric—The golden spice of life. In: Ravindran,
P. ed. Turmeric: The Genus Curcuma. 1st ed. Boca Raton: CRC Press, Taylor &
Francis Group, pp.1–14.
• Ren, X., Zhang, Y., Xiang, Y., Hu, T., Cheng, R. and Cai, H. (2023). The
efficacy of mouthwashes on oral microorganisms and gingivitis in patients
undergoing orthodontic treatment: a systematic review and meta-analysis. BMC
Oral Health, 23(1). https://doi.org/10.1186/s12903-023-02920-4
• Retzepi, M. and Donos, N. (2010). Guided Bone Regeneration:
Biological principle and therapeutic applications. Clinical Oral Implants
Research, 21(6), pp.567–576. https://doi.org/10.1111/j.1600-0501.2010.01922.x
• Rosen, E., Borenstein, R. and Taschieri, S., 2023. Effect of guided tissue
regeneration on endodontic-periodontal lesions: A systematic review.
International Endodontic Journal, 56(2), pp.210–222.

71
 S
• Sadasivuni, K.K., Ahmad, T. and Ponnamma, D., 2022. Lignin mediated
ZnO incorporated biopolymer-based guided tissue regeneration membrane with
antibacterial activity. Frontiers in Chemistry, 10, Article 837858.
• Safi, A., et al., 2024. Comparison of clinical outcomes between guided
tissue regeneration and guided bone regeneration: A systematic review and
meta-analysis. Journal of Clinical Periodontology. Available at:
https://pubmed.ncbi.nlm.nih.gov/38646940/ [Accessed 6 May 2025].
• Şahin, T., Akca, G. and Özmerıç, N. (2024). The role of probiotics for
preventing dysbiosis in periodontal disease: a randomized controlled trial.
Turkish Journal of Medical Sciences, 54(1), Article 40.
https://doi.org/10.55730/1300-0144.5798
• Salazar, C.R., Laniado, N., Mossavar-Rahmani, Y. et al. (2018). Better
diet quality is associated with lower odds of severe periodontitis in US
Hispanics/Latinos. Journal of Clinical Periodontology, 45(7), pp.780–790.
• Sanz, M., Herrera, D., Kebschull, M. et al. (2020). Treatment of stage I–
III periodontitis—The EFP S3 level clinical practice guideline. Journal of
Clinical Periodontology, 47(S22), pp.4–60. https://doi.org/10.1111/jcpe.13290
• Schlagenhauf, U., Jakob, L., Eigenthaler, M. et al. (2016). Regular
consumption of Lactobacillus reuteri-containing lozenges reduces pregnancy
gingivitis: an RCT. Journal of Clinical Periodontology, 43(11), pp.948–954.
https://doi.org/10.1111/jcpe.12606
• Schwalfenberg, G.K. and Genuis, S.J. (2015). Vitamin D, essential
minerals, and toxic elements: Exploring interactions between nutrients and
toxicants in clinical medicine. The Scientific World Journal, 2015, Article ID
318595. https://doi.org/10.1155/2015/318595
• Sensabaugh, C. and Sagel, M.E. (2009). Stannous fluoride dentifrice with
sodium hexametaphosphate: Review of laboratory, clinical and practice-based
data. Journal of Dental Hygiene, 83(2), pp.70–78.
• Shakhsi Niaee, M., Hedayatipanah, M., Torkzaban, P. and Mohammadi,
T. (2024). A chewing gum containing EDTA, MSM and xylitol works
comparable to chlorhexidine mouthrinse. Scientific Reports, 14(1), p.28200.
https://doi.org/10.1038/s41598-024-79551-4
• Shimabukuro, Y., Nakayama, Y., Ogata, Y. et al. (2015). Effects of an
ascorbic acid-derivative dentifrice in patients with gingivitis: a double-masked,

72
randomized, controlled clinical trial. Journal of Periodontology, 86(1), pp.27–
35.
• Shin, Y.W., Bae, E.A., Lee, B. et al. (2007). In vitro and in vivo
antiallergic effects of Glycyrrhiza glabra and its components. Planta Medica,
73(3), pp.257–261.
• Sidabutar, M., Simamora, F.D., Ayu, S., Mahastuti, P. and Laba, M.M.
(2024). The use of the teledentistry application Drgbeta.com to increase access
to oral health services. Journal of International Dental and Medical Research,
17(1), pp.220–226. Available at: http://www.jidmr.com
• Silva, R.F.M. and Pogačnik, L. (2020). Polyphenols from food and
natural products: Neuroprotection and safety. Antioxidants, 9(1), p.61.
https://doi.org/10.3390/antiox9010061
• Sivaramakrishnan, G., Alsobaiei, M. and Sridharan, K. (2021). Powered
toothbrushes for plaque control in fixed orthodontic patients: a network meta-
analysis. Australian Dental Journal, 66(1), pp.20–31.
https://doi.org/10.1111/adj.12798
• Slavin, J. and Carlson, J. (2014). Carbohydrates. Advances in Nutrition,
5(6), pp.760–761. https://doi.org/10.3945/an.114.006650
• Slot, D.E., Valkenburg, C. and Van der Weijden, G.A. (2020).
Mechanical plaque removal of periodontal maintenance patients: a systematic
review and network meta-analysis. Journal of Clinical Periodontology, 47(S22),
pp.107–124. https://doi.org/10.1111/jcpe.13275
• Slots, J. (2004). Systemic antibiotics in periodontics. Journal of
Periodontology, 75(11), pp.1553–1565.
https://doi.org/10.1902/jop.2004.75.11.1553
• Sluijs, E., Slot, D.E., Hennequin-Hoenderdos, N.L., Valkenburg, C. and
Van der Weijden, F.G. (2023). The efficacy of an oscillating-rotating power
toothbrush compared to a high-frequency sonic power toothbrush on parameters
of dental plaque and gingival inflammation: a systematic review and meta-
analysis. International Journal of Dental Hygiene, 21(1), pp.77–94.
https://doi.org/10.1111/idh.12597
• Staudte, H., Sigusch, B.W. and Glockmann, E. (2019). Vitamin C
deficiency and periodontal disease: A systematic review. International Journal
of Dental Hygiene, 17(1), pp.3–12.
T

73
• Tannock, G.W., 1997. Probiotic properties of lactic-acid bacteria: plenty
of scope for fundamental R & D. Trends in Biotechnology, 15(7), pp.270–274.
https://doi.org/10.1016/s0167-7799(97)01056-1.
• Taskan, M.M. and Gevrek, F., 2020. Quercetin decreased alveolar bone
loss and apoptosis in experimentally induced periodontitis model in Wistar rats.
Antiinflammatory & Antiallergy Agents in Medicinal Chemistry, 19, pp.436–
448.
• Tatakis, D.N. and Lee, E., 2021. Crown lengthening surgery: a
comprehensive review of the literature. Journal of Esthetic and Restorative
Dentistry, 33(2), pp.233–241.
• Tatakis, D.N., Trombelli, L. and Wikesjö, U.M.E., 2000. Guided tissue
regeneration: Histologic observations from human studies. Journal of
Periodontology, 71(2), pp.299–309.
• Tavelli, L., McGuire, M.K., Zucchelli, G., et al., 2020. Extracellular
matrix-based scaffolding technologies for periodontal and peri-implant soft
tissue regeneration. Journal of Periodontology, 91, pp.17–25.
• Tilak, J.C., Banerjee, M., Mohan, H. and Devasagayam, T.P., 2004.
Antioxidant availability of turmeric in relation to its medicinal and culinary
uses. Phytotherapy Research, 18, pp.798–804.
• Tonetti, M.S., Eickholz, P., Loos, B.G., Papapanou, P., van der Velden,
U., Armitage, G. et al., 2015. Principles in prevention of periodontal diseases:
Consensus report of group 1 of the 11th European Workshop on
Periodontology. Journal of Clinical Periodontology, 42(S16), pp.S5–S11.
• Tonetti, M.S., Greenwell, H. and Kornman, K.S., 2018. Staging and
grading of periodontitis: Framework and proposal of a new classification and
case definition. Journal of Periodontology, 89(Suppl 1), pp.S159–S172.
• Tonetti, M.S., Jepsen, S., Jin, L. and Otomo-Corgel, J., 2017. Impact of
the global burden of periodontal diseases on health, nutrition and wellbeing of
mankind: a call for global action. Journal of Clinical Periodontology, 44(5),
pp.456–462.
• Trombelli, L., et al., 2023. Flap surgery for periodontal pockets: A
comparative clinical study. Journal of Clinical Periodontology, 50(3), pp.301–
308.
U

74
• Urban, I.A., Lozada, J.L., Jovanovic, S.A., Nagursky, H. and Nagy, K.,
2019. Vertical ridge augmentation with titanium-reinforced, dense PTFE
membranes and a combination of particulate autogenous bone and anorganic
bovine bone-derived mineral. International Journal of Oral & Maxillofacial
Implants, 34(1), pp.179–189.
V
• Van Dyke, T.E., 2017. Pro-resolving mediators in the regulation of
periodontal disease. Molecular Aspects of Medicine, 58, pp.21–36.
• Vaquette, C., Fan, W., Xiao, Y., et al., 2012. A biphasic scaffold design
combined with cell sheet technology for simultaneous regeneration of alveolar
bone/periodontal ligament complex. Biomaterials, 33, pp.5560–5573.
• Varela-López, A., Giampieri, F., Bullón, P., Battino, M. and Quiles, J.L.,
2016. Role of lipids in the onset, progression and treatment of periodontal
disease: A systematic review of studies in humans. International Journal of
Molecular Sciences, 17, p.1202.
• Varoni, E., Tarce, M., Lodi, G. and Carrassi, A., 2012. Chlorhexidine
(CHX) in dentistry: State of the art. Minerva Stomatologica, 61, pp.399–419.
W
• Wang, H.L. and Boyapati, L., 2006. “PASS” principles for predictable
bone regeneration. Implant Dentistry, 15(1), pp.8–17.
• Weijden, F., Slot, D.E., van der Sluijs, E. and Hennequin-Hoenderdos,
N.L., 2022. The efficacy of a rubber bristles interdental cleaner on parameters
of oral soft tissue health – a systematic review. International Journal of Dental
Hygiene, 20(1), pp.26–39. https://doi.org/10.1111/idh.12492.
• Wen, W., Chau, E., Jackson-Boeters, L., et al., 2010. TGF-β1 and FAK
regulate periostin expression in PDL fibroblasts. Journal of Dental Research, 89,
pp.1439–1443.
• Wolbach, S. and Bessey, O.A., 1942. Tissue changes in vitamin
deficiencies. Physiological Reviews, 22, pp.233–279.
• Worthington, H.V., MacDonald, L., Poklepovic Pericic, T., Sambunjak,
D., Johnson, T.M., Imai, P., et al., 2019. Home use of interdental cleaning
devices, in addition to toothbrushing, for preventing and controlling periodontal
diseases and dental caries. Cochrane Database of Systematic Reviews, 4(4).
X

75
• Xiao, E., Mattos, M., Vieira, G.H. and Graves, D.T., 2024. Bone loss and
inflammation in periodontal disease. Frontiers in Microbiology, 15, p.1469414.
Y
• Yang, M., Gao, X., Shen, Z., et al., 2019. Gelatin-assisted conglutination
of aligned polycaprolactone nanofilms into a multilayered fibre-guiding scaffold
for periodontal ligament regeneration. RSC Advances, 9, pp.507–518.
• Yao, S., Chen, L. and Huang, Y., 2023. The role of vitamin C
supplementation in healing after periodontal flap surgery. Scientific Dental
Journal, 7(3), pp.112–118.
• Yar, M., Farooq, A., Shahzadi, L., et al., n.d. Novel meloxicam releasing
electrospun poly-[incomplete citation – journal name, year, volume and pages
needed to complete this reference].
• Yechiel, G., Liron, G. and Nurit, B., 2014. Efficacy of PerioChip® in the
treatment of chronic periodontitis: A randomized controlled trial. Journal of
Applied Oral Science, 22(4), pp.287–294.
Z
• Zeng, Y., Nikitkova, A., Abdelsalam, H., Li, J. and Xiao, J., 2019.
Activity of quercetin and kaempferol against Streptococcus mutans biofilm.
Archives of Oral Biology, 98, pp.9–16.
• Zhou, Y., Liu, L. and Zhang, W., 2021. Systemic conditions and
periodontal disease: Interplay and implications. Frontiers in Cellular and
Infection Microbiology, 11, p.766944.
• Zong, G., Holtfreter, B., Scott, A.E., Völzke, H., Petersmann, A.,
Dietrich, T., Newson, R.S. and Kocher, T., 2016. Serum vitamin B12 is
inversely associated with periodontal progression and risk of tooth loss: A
prospective cohort study. Journal of Clinical Periodontology, 43, pp.2–9.

76
77
78