describes the current evidence on novel approaches in non surgical periodontal therapy

1. Novel approaches in non-
surgical periodontal
therapy
Dr. Lakkireddy Vasavi reddy
II MDS

2. Contents: • Introduction
• Air-powder polishing
• Photodynamic therapy
• Lasers
• Biofilm decontamination
approach
• Perioprotect
• Ozone therapy
• Hyperbaric oxygen therapy
• H2O2 photolysis
• Bioelectric effect
• Extracorporeal shock wave
therapy
• Electrical stimulation of
osteogenesis.
• Antioxidants
• Bisphosphonates
• Statins
• Proresolving mediators
• Gene therapy
• Nanotechnology
• Hyaluronic acid
• Naturoceutics/ phytotherapy.

3. Introduction:
Periodontitis……sub-gingival microbiota…
- SRP…gold standard treatment

4. Air powder polishing:
Air-polishing devices using a low abrasive
powder have become a promising alternative
in recent years.

5. study Purpose conclusion
Petersilka - 2003 To evaluate the efficacy of a new air-polishing powder(glycine) in
subgingival plaque removal at interdental sites during periodontal
maintenance therapy
In periodontal maintenance therapy, air-polishing with glycine-based powder is more
effective than hand instrumentation in removing subgingival plaque at interdental sites
with up to 5 mm probing depth, in addition to being timeefficient and safe
Petersilka - 2003 To evaluate the efficacy of subgingival plaque removal in buccal and lingual
sites during supportive periodontal therapy with a glycine-based air-
polishing powder
In supportive periodontal therapy, air-polishing with glycine-based powder is more effective
than hand instrumentation in removing subgingival biofilm from periodontal pockets of 3–5
mm in depth, and offers greater patient comfort
Flemmig TF- 2007 To evaluate the subgingival debridement efficacy of glycine powder
airpolishing in periodontal pockets of various depths, in order to determine
the method’s potential application in supportive periodontal therapy
Glycine powder air-polishing for 5 seconds per surface is effective and time efficient in
removing subgingival biofilm in periodontal pockets with a probing depth of approximately
4 mm
Petersilka - 2008 To evaluate the safety and efficacy of glycine powder in comparison with
sodium bicarbonate powder and hand instrumentation on gingival
epithelium in vivo, using histological analysis
Glycine powder air-polishing is safe and causes less gingival erosion than hand
instrumentation and sodium bicarbonate air-polishing
Moëne R- 2010 To evaluate patient acceptance, the safety and the short-term
microbiologic effect of the AIR-FLOW® PERIO Method in subjects on
maintenance care, with residual pockets of ≥ 5 mm
Subgingival air-polishing with AIR-FLOW® PERIO is more time efficient than hand
instrumentation Air-polishing is safe and more acceptable for the patients
Flemmig TF- 2011 To evaluate the efficacy and safety of subgingivally applied glycine powder
air-polishing in removing bacterial biofilm in moderate to deep periodontal
pockets, in comparison to conventional scaling and root planing (SRP)
Subgingival glycine powder air-polishing with AIR-FLOW® PERIO is more effective in
removing subgingival biofilm in moderate to deep periodontal pockets than scaling and root
planing The method is safe and comfortable for patients Full-mouth glycine powder air-
polishing may result in a beneficial shift of the oral microbiota
Wennström JL-
2011
To evaluate the clinical and microbiological effects and perceived
treatment discomfort of root debridement by subgingival air-polishing in
comparison with ultrasonic instrumentation in patients on supportive
periodontal therapy (SPT)
No significant differences in clinical or microbiological outcomes were observed between
the two methods of subgingival root debridement of moderate/deep
periodontal pockets, in supportive periodontal therapy patients
Lu et al - 2018 to evaluate the effect of supragingival glycine air polishing (SGAP) on the
subgingival periodontal pathogens during maintenance therapy and to
check the association of periodontal pathogens and clinical parameters.
Supragingival glycine air polishing had a reliable effect in removing subgingival dental plaque
biofilm during maintenance period, and three months may be a proper maintenance
interval for pockets not more than 5 mm.
Tsang et al - 2018 to investigate the effect of subgingival GPAP as an additional approach to
nonsurgical periodontal treatment in subjects with chronic periodontitis.
GPAP, as an additional approach to nonsurgical periodontal treatment, may be beneficial for
the short- term improvement of subclinical inflammation when measured by gingival
crevicular fluid volume

6. Sculean et al reviewed current evidence from the literature during a consensus conference held during the
Europerio 7 Congress in Vienna (2012)
RESULTS
• Air-polishing devices have shown to be efficient in removing both sub and supragingival biofilm and stains
• The new generation of powders and devices with subgingival nozzles provide better access to subgingival and
interdental areas
• In shallow pockets up to 4 mm and in deeper pockets ≥ 5 mm, air-polishing removes biofilm significantly more
efficiently than hand curettes
• Full-mouth glycine powder air-polishing results in a significantly decreased load of Porphyromonas gingivalis in
the oral cavity
• Subgingival biofilm removal with air-polishing is considerably faster than hand instrumentation or ultrasonics
• Glycine-based air-polishing is perceived as more comfortable by the patients than hand instrumentation or
ultrasonics
• Subgingival air-polishing with glycine-based powder is safe if used as per recommendation.
CONCLUSION: Subgingival air-polishing with the new generation of powders is efficient, fast, comfortable and
safe.

7. Consensus Conference Findings on Supragingival and Subgingival Air Polishing.
Cobb et al- 2017
The conference reported the following conclusions:
1) Supra- and subgingival air polishing using glycine powder is safe and effective for removal of
biofilms from natural tooth structure and restorative materials;
2) there is no evidence of soft-tissue abrasion when using glycine powder in an air-polishing
device;
3) in periodontal probing depths of 1 mm to 4 mm, glycine-powder air polishing, using a standard
air-polishing nozzle, is more effective at removing subgingival biofilm than manual or ultrasonic
instruments; and
4) at probing depths of 5 mm to 9 mm, using a subgingival nozzle, glycine powder air polishing is
more effective at removing subgingival biofilm than manual or ultrasonic instrumentation.

8. Erythritol:
• Erythritol can be found naturally in many organisms, which indicates that it is a byproduct of metabolism of
sugar. Erythritol is normally made from glucose that is created from corn or wheat starch.
• The starch is first treated with enzymes (special proteins) that break the starch down into glucose. This
glucose is then mixed with yeast, such as Moniliella pollinis or Trichosporonoides megachliensis, and the
yeast ferments the glucose to form erythritol.
• Muller in 2014 evaluated repeated subgingival air-polishing in residual pockets with a new erythritol powder
containing 0.3% chlorhexidine. The results showed no significant differences between test and control group
and concluded that repeated subgingival air-polishing reduced the number of pockets >4 mm similar to
ultrasonic debridement. It was safe and induced less pain.
• Hagi et al in 2015 evaluated erythritol powder (EPAP) influence on the clinical and microbiologic parameters
over a period of 6 months in patients undergoing supportive periodontal therapy. The subgingival use of
EPAP by means of an air-polishing device may be considered safe and may lead to comparable clinical and
microbiologic outcomes to those obtained with SRP.

9. Trehalose powder
• Non-cariogenic disaccharide approved for use in food processing.
• it is highly water soluble (689 g/l) with a pH of 6.4.
• abrasive effect on tooth substance- as low as a glycine formula while
having comparable particle diameters of 25– 35 µm.
• Kruse et al (2019) compared trehalose powder for subgingival air-polishing
with sonic debridement in residual periodontal pockets during
maintenance therapy. He concluded that Subgingival air-polishing with
trehalose powder showed comparable clinical outcomes to sonic scaling.
Sonic scaling evoked more discomfort compared to air-polishing.

10. Bioglass:
• Sultan et al in 2019 evaluated the use of novel bioglass powder on root
surface. He stated that the AP with BioMinF spherical particles may be
preferred to the conventional NaHCO3, in light of the benefitsof using
bioactive glasses and the more conservative behaviour of the glass
particles observed following polishing

11. Systematic reviews:
Buhler –2014- in a systematic review on effects of air polishing on oral tissues conluded that
consistent evidence suggests that sodium bicarbonate powders should not be used in
periodontally affected dentitions because of their considerable potential of harm to cementum,
dentine and gingiva. There is consistent evidence demonstrating less potential of harm on soft and
hard periodontal tissues of powders consisting of glycine and can be safely used.
Zhang et al – 2019- in systematic review evaluated the effect of subgingival debridement by
ultrasonic debridement (UD) in comparison with subgingival air polishing (SubGAP) during
periodontal maintenance and concluded that The clinical efficacy of SubGAP compared with that
of UD for periodontal maintenance remains inconclusive on account of limited evidence. To date,
neither SubGAP nor UD showed superior clinical effect when compared. High-quality, well-
designed clinical studies are still needed to ascertain the long-term clinical stability.

12. Photodynamic
therapy:
• It is based on the principle that the photosensitizer
(photoactivatable substance) binds to the targeted cells and
then can be activated by light of the appropriate wavelength in
the presence of oxygen. This results in the generation of singlet
oxygen and free radicals, which are extremely toxic to certain
cells and bacteria.
• The use of photodynamic therapy was first reported by a
Danish physician, Niels Finsen. In 1978, studies by Thomas
Doughtery and co-workers showed striking results from clinical
testing of this therapy employed on malignant tumours.
• Inactivation of microorganisms using photodynamic therapy
has been defined as either antimicrobial photodynamic
therapy (aPDT), photodynamic antimicrobial chemotherapy
(PACT) or photodynamic disinfection.
• Methylene blue mediated aPDT (Periowave) is an example of
PDT employed in periodontics

13. • The two main components of photodynamic therapy are source of
light and photosensitizer dye.
Chemical name of
photosensitizer
Trade
name
Commercial
source
Wavelength of light
used
Indocyanine green Periogreen® Elexxion 820 nm
Hematoporphyrin derivative Photofrin® Axcan pharma 632 nm
Benzoporphyrin derivative
monoacid ring-A
Visudyne® QLT Inc. and Novartis
opthalmics
690 nm
5- Aminolevulinic acid Levulan® DUSA pharmaceuticals
Inc.
632 nm
Methylaminolevulinate Metvix® Galderma 632 nm
Meta-tetra hydroxyphenyl
chlorine
Foscan® Biolitec AG 652 nm

15. Systematic review Conclusion
Azarpazhooh et
al., 2010
aPDT as an independent treatment or an adjunct therapy to SRP was
not superior to SRP
Atieh et al., 2010 The use of aPDT in conjunction with SRP was associated with
significant clinical parameter improvements
Sgolastra et al.-
2013
The use of aPDT adjunctive to conventional treatment provided short-
term benefits. There was no evidence of effectiveness for the use of
aPDT as an alternative to SRP
Smiley et al., 2015 aPDT with a diode laser adjunctive to SRP had a beneficial effect with
a moderate level of certainty

16. Systematic review Conclusion
Vohra et al 2016 aPDT is effective as an adjunct to SRP for the management of AgP, however,
further randomized clinical trials with well defined control groups are needed in
this regard.
Franco et al - 2018 it was not possible to state that repeated applications of aPDT, in association with
non-surgical treatment of residual pockets, have effective clinical effects in the
periodontal maintenance therapy. Although one can consider that aPDT is a
promising adjuvant therapy, it is still necessary to carry out more RCTs with low
risk of bias in order to confirm or refute the benefits of multiple applications for
residual periodontal pockets.
Peron et al- 2019 Although our results suggest that PACT (Photodynamic antimicrobial
chemotherapy) displays antimicrobial action on P. gingivalis, thus improving the
PD, a nonuniformity in the PACT protocol and the limited number of studies
included lead to consider that the bactericidal efficacy of PACT against
periodontal pathogens in PD remains unclear.

17. Biofilm decontamination
procedure:
• Desiccant is a simple liquid solution that
contains a concentrated blend of
sulphonic/sulphuric acids. (Hybenx gel)
• These acids have a strong affinity to bind to
the water present in the biofilm matrix and to
quickly detach, destroy, and eradicate the
biofilm

18. Prini-Prato in 2016 in a case report treated acute periodontal abscess with Hybenex positioned into the pocket on the root
surface with no instrumentation and systemic antibiotics and concluded that biofilm decontamination approach was promising
treatment for acute periodontal abscess and local application of this material avoids systemic or local antibiotics.
Lombardo in 2015 evaluated the clinical and microbiological effects of the adjunctive administration of a locally delivered
desiccant liquid with molecular hygroscopic properties (HYBENX® Oral Tissue Decontaminant™; HBX) in association with sub-
gingival ultrasonic debridement (UD) and concluded that a decreased inflammatory signs and reduction of the bacterial load can
be obtained in the short term by topical association of the desiccant agent HBX with UD.
Bracke et al in study showed that the combined adjunctive treatment with SRP indicated a complete absence of detectable
bacterial DNA (13 species) and the four inflammatory mediators (MMP8, IL-1ß, IL-6, and TNF-alpha) from samples taken from
the gingival sulci treated with HBX.
Isola in 2018 conducted a RCT using desiccant agent in treatment of periodontitis and conclude that scaling and root planning
plus desiccant resulted in greater reduction in clinical, microbial and inflammatory mediators compared to SRP alone.
Shantipriya reddy et al in 2018 evaluated the treatment effect of the biofilm decontamination approach on acute periodontal
abscesses in patients on periodontal maintenance therapy and concluded that this novel approach of Biofilm Decontamination
using HYBENX® gel seems to be a very promising technique for the treatment of acute periodontal abscess, having an added
advantage of avoiding the use of any systemic or local antibiotics.

19. Boric acid gel:
New antibacterial
compounds that
contains boron.It plays a
role in inflammatory and
immune response
regulation
It also plays a vital role
in osteogenesis and the
maintenance of bones.
Bone regeneration and
development are
adversely affected in
boron deficiency,
increasing the risk of
bone loss.
regulate the oxidant–
antioxidant level of the
affected tissue through
gulathione ,decreases
lipid peroxidation and
enhances the
antioxidant defense
mechanism and vitamin
levels.
Borinic acid quinoline esters are a
recently‐identified class of new antibacterial
and anti‐inflammatory compounds known to
inhibit osteoclastic bone resorption.

20. Luan et al in 2008 tested potential effectiveness of 1% topical boron in treating periodontal disease. The
results indicated that boron application significantly reduces the formation of an inflammatory infiltrate and
reduces bone loss, measured histologically and by micro-CT.
Demirer in 2012 evaluated the histopathologic and morphometric effects of systemic boric acid in a rat
periodontitis model. They demonstrated that systemic administration of boric acid reduced periodontal
inflammation and alveolar bone loss in periodontal disease in rats.
Saglum in 2013 in a randomized clinical trial evaluated the effects of boric acid irrigation as an adjunct to
scaling and root planing. They suggested that boric acid could be an alternative to chlorhexidine, and it might
be more favorable because boric acid was superior in whole‐mouth BOP as well as PD and CAL reduction for
moderate pockets in early time periods.
Kanoriya in 2017 in a RCT evaluated the effects of the subgingival delivery of 0.75 % boric acid gel as an
adjunct to SRP. They concluded that BA as an adjunct to SRP can provide a new insight into therapeutic
strategies for the management of CP, but further clinical evaluations are needed.

21. Perioprotect:
• PerioProtect is a comprehensive method customized for individual patients to help
manage biofilms growing in the spaces or pockets between teeth and gum tissue.
• The method is a combination of treatments, including a non-invasive chemical debriding
therapy used in conjunction with traditional mechanical debriding procedures.
• The chemical therapy involves a tray delivery of doctor-prescribed solutions to chemically
debride biofilm from the periodontal pocket and alter the pocket's microbiological
environment to disrupt biofilm growth.
• Hydrogen peroxide gel, locally administered using PerioProtect (prescription customized
trays) in the treatment of subjects with moderate to advanced periodontitis has shown
statistically significant clinical improvements in pocket depths and bleeding when
compared with Scaling and root planing alone.

22. • Mark S. Putt in 2012, the adjunctive-3
months-1.7% hydrogen peroxide gel, locally
-PerioProtect (prescription customized
trays)-moderate to advanced periodontitis-
statistically significant clinical improvements
in pocket depths and bleeding when
compared with SRP alone

23. laser therapy:
• Its hard tissue applications are also comparatively increasing as an adjunct or as an
alternative to conventional scaling and root planing procedures.
• Erbium-doped Yttrium Aluminium Garnet (Er YAG), Neodymium-doped Yttrium
Aluminium Garnet (Nd YAG), CO2 and Erbium Chromium: Yttrium-Scandium-Gallium
Garnet (Er YSGG) lasers are all explored for hard tissue applications. Out of these, Nd YAG
laser have shown to induce undesirable changes on the root surface.
• Nd YAG and CO2 laser induces charring and melting, but CO2 laser is advantageous if
proper parameters are followed .
• Neodymium-doped Yttrium Aluminium Perovskite (Nd YAP) laser was found to be equally
efficacious as traditional SRP (scaling and root planing).
• In contrast, Er YAG laser has been proved to be beneficial and in combination therapy it
has led to a notable improvement in all clinical parameters

26. • Review by Sumra et al in 2018 states that Er YAG laser is a viable
option for non-surgical periodontal therapy if proper parameters are
followed i.e. the energy in the range of 140–160 mJ and frequency of
10 Hz because at a lesser energy level of 100–120 mJ and 6.5 Hz laser
is not effective with no superiority over conventional procedures and
at higher energy levels of 300 mJ it presents large and deep grooves
with maximum number of craters on the root surface. Nd YAG and
CO2 laser should be avoided because they cause more harm than
good and they offer no additional advantage in any of the clinical
parameters which were assessed.

27. Laser Technology to Manage Periodontal Disease:
A Valid Concept?
Sameul et al 2014
• Conclusion:
Studies utilizing laser technology may demonstrate positive effects on
1) selectively decreasing the biofilm environment,
2) removing calculus deposits and neutralizing endotoxin,
3) removing sulcular epithelium to assist in reattachment and
decreased pocket depth, and
4) biostimulation for enhanced wound healing. Comparisons of studies
to determine the difference between lasers and their respective effects
on the periodontium are difficult to assess due to a wide variation of
laser protocols.

28. Bio-electric effect:
• The bioelectric effect is the synergistic killing effect observed on
biofilm cells that are exposed to antibiotics in the presence of an
electric direct current (DC) or alternating current (AC) field.
• Direct current fields of 1.5 to 20 volts and current densities of 2-5 mA/cm2.
• 12-24hrs of application time.

29. Blenkinsopp et al (1992) Used electric fields to enhance the efficacy of antibiotics in killing bacterial biofilm
Costerton et al reported that application of a low-intensity direct current (max. 2.1 mA/cm 2 ) to a flow cell in which
Pseudomonas aeruginosa biofilm had been established was relatively ineffective in reducing bacterial numbers alone, but
increased the killing efficacy of tobramycin by over four orders of magnitude when the two modalities were applied concurrently
Padmini et al in 2018 In an invitro study investigated i if the subgingival plaque biofilm resistance can be reduced using
doxycycline in the presence of low-intensity electric field (bioelectric effect).It was concluded that the ability of doxycycline
antibiotic in inhibiting plaque biofilm was significantly enhanced by application of a weak electric field (5 volts for 2 min).
Lasserre et al in 2015 studied the influence of low electric direct currents (DC) on chlorhexidine (CHX) efficacy against the
periodontal pathogen Porphyromonas gingivalis within a biofilm and showed a significant enhancement of the chlorhexidine
0.2% efficacy against P.gingivalis was observed when applying 10mA currents.
Del Pozo et al in a systematic review (2008) reported that it has been shown how the application of direct electric current alone
can provoke surface detachment of bacterial biofilms but it is not clear which electric parameters are important and the optimal
antimicrobial concentration to achieve the maximum effect remains to be defined.

30. Extra corporeal shock wave therapy:
• Extracorporeal shock waves are high-energy acoustic waves generated
under water with high-voltage explosion and vaporization.
• ESWT has been shown to have bactericidal effect on several
microorganisms including A aureus. S epidermidis. Pseudomonas
aerogenosa.
• Shock waves stimulate the early expression of angiogenesis-related
growth factors, including endothelial nitric oxide synthase (eNOS),
(VEGF), and proliferating cell nuclear antigen (PCNA), contributing to
induced vascularization and improving blood supply, with increased cell
proliferation and tissue regeneration and repair

32. For:
• Gerdesmeyer et al 2005 – reported
antibacterial effect on application
of shock waves of 2Hertz energy
and at least 1000 impulses.
• Novak et al 2008 reported
bactericidal effect of selective
species in oral biofilm with energy
as low as 0.3J/mm2 and only
100impulses
• Gnanadas et al. Successful
treatment of biofilm infections
using shock waves combined with
antibiotic therapy
Against:
• Kerfoot et al 1992 reported no
bactericidal effect.
• Sathish kumar et al 2008 that
single application of ECSWT could
not overcome the P. gingivalis
infection

33. Electrical stimulation on osteogenesis of alveolar
bone :
• Use of electrial stimulation for osteogenesis in medicine in non-union of
fracture, regeneration of partial limb.
Effects:
Undifferentiated mesenchymal cells to osteoblasts
Increase growth factors
Increase calcium and phosphate ions at cathode
Increase cyclic nucleotides.

34. Author Work done Reported
Yoshimura et al GTR enhanced EMF Reported alveolar bone
defect treated showed
better results compared
to controls.
Hwang et al Biphasic direct current
(BCS) has been found to
enhance osteogenesis,
and could be applied
clinically to the early
bone formation around
implants.

35. Periodontal vaccines:
Periodontal immunization can be active or passive
Active immunization:
•Whole bacterial cell
•Subunit vaccine
•Synthetic peptides
Passive immunization
•Murine monoclonal antibodies
•Plantibodies
Genetic immunization
•Plasmid vaccines
•Live, viral vector vaccines

36. • The virulence factors of P. gingivalis which have been used as subunits for the development
of active immunization are:
• outer membrane protein,
• gingipains,
• fimbriae and
• heat shock protein.
Three types of vaccines were employed for the control of periodontal diseases. These include
the vaccines prepared from pure cultures of streptococci and other oral organisms;
autogenous vaccines; stock vaccines such as Vancott's vaccine, Goldenberg's vaccine, or Inava
endocarp vaccine.

37. study conclusion
Hardham et al. a study to evaluate the immunogenic properties and vaccine performance of a monovalent canine periodontal disease vaccine in
the mouse oral challenge model of periodontitis. They prepared experimental vaccines from formalin, heat, or aeration-
inactivated cultures of Porphyromonas gulae . Based on the results of the study, the authors concluded that a periodontal
vaccine may be a useful tool in preventing the progression of periodontitis in animals.
Lee et al. A study to evaluate the performance of P. gingivalis HSP60 as a vaccine candidate. Rats were immunized with P. gingivalis HSP60,
and experimental alveolar bone loss was induced by the infection with multiple periodontopathogenic bacteria. Results showed
a very strong inverse relationship between postimmune anti-P. gingivalis HSP immunoglobulin G (IgG) levels and the amount of
alveolar bone loss induced by either P. gingivalis or multiple bacterial infection.
Genco et al. studied the effects of immunization with invasive or noninvasive P. gingivalis strains on the pathogenesis of infection in a mouse
chamber model. They concluded that immunization with invasive P. gingivalis A7436 and W83 or noninvasive P. gingivalis 33277,
HG405, and 381 protected mice from secondary lesion formation and death after challenge with invasive P. gingivalis A7436 or
W83. P. gingivalis-specific antibody did not, however, inhibit the colonization of P. gingivalis within chambers.
Miyachi et al. a study to clarify the effect of arginine-specific-gingipain A (rgpA), a DNA vaccine that could prevent alveolar bone loss in mice.
The results of this study suggested that immunization with rgpA DNA vaccine via the nasal cavity is an effective method for
preventing alveolar bone loss incurred by infection with P. gingivalis.
Yonezawa et
al.
in a study evaluated the protective potential of rgpA DNA vaccine against a lethal challenge of P. gingivalis and also analyzed the
induction of cellular immune responses by the DNA vaccine. Based on the results, it appeared that immunization with the rgpA
DNA vaccine may induce both humoral and cellular immune responses for protection against P. gingivalis challenge, further
demonstrated that attenuated excessive interferon-γ production in animals immunized with an rgpA DNA vaccine may play a key
role in protection against P. gingivalis infection.
DeCarlo et al. conducted an experiment in a rat periodontitis model to investigate the use of P. gingivalis binding domain, recombinant heme
acquisition rHA2 as an immunogen for periodontitis vaccine. It was concluded that subcutaneous administration of rHA2,
without addition of adjuvant, stimulated an immune response which was significant enough to provide some clinical protection
from periodontitis.

38. Choi et al. studied the effect of immunization with a P. gingivalis fimbrial protein, a capsular polysaccharide (CPS), or a
CPS-fimbrial protein conjugate vaccine and compared their effects in human peripheral blood lymphocytes
severe combined immunodeficiency mice. They concluded that CPS-fimbrial protein conjugated from P.
gingivalis could potentially be developed as a vaccine against periodontal infection by P. gingivalis.
Houri-Haddad et al. a study to test the hypothesis that different adjuvants in P. gingivalis vaccines would differentially modify the host
response to a live P. gingivalis infection. Results showed that vaccination with P. gingivalis in alum attenuated the
pro-inflammatory cytokine levels at the site of infection, while the vaccine containing incomplete Freund's
adjuvant did the opposite. Although both vaccines induced a similar humoral IgG response, P. gingivalis-induced
abscesses were significantly smaller in the alum-adjuvant group. Therefore, the authors concluded that the
immune response and the resultant protection to a P. gingivalis infection, in P. gingivalis-vaccinated mice, are
adjuvant-dependent.
O'Brien-Simpson et
al.
a study to show that P. gingivalis W50 whole cells exhibit the same binding pattern to fibrinogen, fibronectin,
hemoglobin, and collagen Type V as the arginine- and lysine-specific cysteine protease complex (RgpA-Kgp
complex), which binds to these proteins with nanomolar dissociation constants. They also showed that the
adhesins of the RgpA-Kgp complex are important in providing protection in the murine lesion and periodontitis
models when the complex is used as a vaccine and that the immune response is predominately a Th2 response.
The results suggested that when the RgpA-Kgp complex or functional binding motif, or active site peptides are
used as a vaccine, they induce a Th2 response that blocks function of the RgpA-Kgp complex and protects against
periodontal bone loss.
Huang et al. in 2019 have used a novel technique of cell free protein synthesis as a platform to produce vaccine
candidates. They were able to recombinantly generate a cocktail of P.gingivalis proteins that were capable of eliciting a
high serum IgG response as well as were capable of protecting the mice from progressive bone loss.

39. Systematic reviews:
Dhingra K and Vandana KL in 2010 published a systematic review of preclinical studies of Prophylactic vaccination
against periodontal disease where only two randomized controlled animal trials qualified, and they reported exactly
opposite effects of vaccine administration in Macaca fascicularis experimental periodontitis models by
administration of two different agents (i.e., a negative effect with combined whole-cell antigens of Porphyromonas
gingivalis and Prevotella intermedia in contrast to a positive effect with cysteine proteases of P. gingivalis).They
concluded that due to the insufficient quantity and quality of animal trials, no adequate evidence could be gathered
to use the beneficial effects of these animal experiments to formulate a prophylactic human periodontal vaccine.
A systematic review by Meenakshi et al in 2020 evaluated 48 studies on periodontal vaccines and concluded that
studies evaluating Porphyromonas gingivalis are the most common and the structures showing the most potential as
a vaccine candidate are Outer membrane proteins, fimbriae and gingipains, the structure having the least potential
is Lipopolysaccharide.

40. Limitations:
• The intricacy of the periodontopathic bacteria might be a problem as
a substantial number of bacteria appears to be involved in
periodontal disease.
• bacterial whole cells or crude extracts preparation for vaccination is
not desirable because the antigenic determinants of bacteria
potentially possess a high risk of cross reactivity with human
counterparts.
• Vaccines may be contaminated with unwanted proteins or toxins, or
even live viruses.

41. Ozone therapy:
• Ozone as a disinfectant in medicine was first used and introduced by Landler in 1870 and in
year 1932, Dr. E.A.Fisch- a swiss dentist had the first idea to use ozonated water or gas in his
practice.
• Ozone is a powerful oxidizer - it effectively kills bacteria, fungi, viruses, and parasites at a
dramatically lower concentration and no toxic side effects.
• Along with antihypoxic effect of reducing inflammatory processes, ozone causes synthesis of
biologically active substances such as interleukins, leukotrienes, and prostaglandins which are
beneficial in reducing inflammation and promote wound healing.
• Ozone can be used in the form of Ozonated Water, Gaseous Ozone or Ozonized oils.
• HealOzone®, OzonyTron®, Prozone® are some commercially available appliances used for
ozone production in dental treatment.

42. Mechanism
of action:

43. • Karin C Hutch., et al. investigated whether gaseous ozone and aqueous
ozone exerted any cytotoxic effect on human oral epithelial cells (BHY)
and gingival fibroblasts (HGF-1) compared with established antiseptic.
• Ozone gas was found to have toxic effects on both cell types. No
cytotoxic signs were observed for aqueous ozone.

44. STUDY PURPOSE RESULTS
Ebensberger et al.
(2002)
To investigate the effects of irrigating
ozonated water on the proliferation of cells
in the periodontal ligament attached to
roots of extracted human teeth.
Irrigation with ozonated water showed high rates of cells in comparison to
saline solution (control group), but with no significant differences. There were
no differences in the number and distribution of positive PCNA cells in the
coronal and apical part of the roots of the cuspid teeth.
de Ramon e t al.
(2004)
To analyze the clinical, microbiological a n d
immunological responses in patients with
moderate/severe periodontal pockets using
ozone therapy
Ozone had no significant effect on the removal of supragingival plaque, but
reduced the gingival bleeding index, including TNF-alfa and IL-1_. However, it
did not produce changes in the level of periodontal insertion and pocket
depth.
Martínez Abreu &
Abreu Sardiñas
To evaluate the effects of ozonated oil
(Oleozon) in the treatment of moderate
periodontitis.
Improvement of the signs and symptoms was faster in the group treated with
ozonated oil than in the control group. Microbial levels were more compatible
with healthy periodontium in the ozonated group.
Ramzy et al (2005) to assess the clinical and antimicrobial
effect of ozonized water in management of
aggressive periodontitis.
High significant improvement regarding pocket depth plaque index gingival
index and bacterial count was recorded related to quadrants treated by
scaling and rootplaning together with ozone application. They also reported
signicant reduction in bacterial count in sites treated with ozonized water
Huth et al. (2007) To investigate the effects of aqueous ozone
on the NF-kB system.
Aqueous ozone had inhibitory effects on the NF-κB system, suggesting it has
anti-inflammatory properties.

45. study purpose conclusion
Kshitish & Laxman
(2010)
To evaluate and to compare the effects of
irrigating ozonated water (0.082 mg/h for 5-10
minutes) and 0.2% chlorhexidine (Control
group) in clinical parameters such as gingival
index and gingival b leeding index, in addition to
the action of ozone on oral microorganisms
Reduction of the gingival index and bleeding index in the ozone group
was significant in comparison to chlorhexidine. Ozone is a powerful
agent in the inactivation of microorganisms associated to periodontitis.
Skurska et al. (2010) A comparison of the clinical condition and
salivary levels of MMP (Matrix
metalloproteinase) after scaling and root
planing or ozone therapy in patients with
aggressive or c hronic periodontitis.
scaling and root planing (SRP) combined with ozonetherapy does not
contribute to further improvement in clinical periodontal parameters
in patients with aggressive and chronic periodontitis. Ozonetherapy
combined with SRP leads to a decrease of saliva MMP concentration in
patients with aggressive periodontitis.
Huth et al. (2011) To investigate the antimicrobial effectiveness of
aqueous and gaseous ozone in comparison to
the antiseptic chlorhexidine digluconate on
periodontal microorganisms in planktonic state
and in biofilm.
Gaseous ozone presented greater antimicrobial activity against
Aggregatibacter actinomycetemcomitans. Chlorhexidine, aqueous and
gaseous ozone showed dosedependent effectiveness; however, there
was g reater efficacy in planktonic bacteria than in biofilm.
Hayakumo (2012) to evaluate the clinical and microbiological
effects of NBW3 irrigation as an adjunct to
subgingival debridement for periodontal
treatment.
suggests that subgingival irrigation with NBW3 may be a valuable
adjunct to periodontal treatment.
Habashneh et al
(2014)
to determine the clinical and biological effects
of the adjunctive use of ozone in nonsurgical
periodontal treatment.
Irrigation with ozonated water as an adjunctive therapy to SRP
produces no statistically significant benefit compared with SRP plus
distilled water irrigation.

46. study purpose conclusion
Uraz et al (2018) to evaluate the clinical, biochemical
and microbiological efficacy of ozone
treatment as an adjunct to scaling and
root planing (SRP) in generalized
chronic periodontitis (GCP) patients.
adjunctive ozone therapy did not provide additional benefits to
clinical, microbiological (Pg, Tf, Pi) and biochemical parameters
over SRP in chronic periodontitis patients.
Tasdemir et al
(2019)
To evaluate the effects of ozone
therapy on clinical and biochemical
parameters of moderate to severe
generalized periodontitis patients after
non‐surgical periodontal therapy.
Ozone therapy did not have any additional effect on
periodontal parameters. All cytokines were reduced after
periodontal therapy. all the inflammatory parameters
(pentraxin‐3 (PTX‐3), interleukin‐1β (IL‐1β), and high sensitivity
C‐reactive protein (Hs‐CRP) reduced at 3- month followup ,only
PTX‐3 levels were significantly lower at ozone sites compared to
those at the control sites.
Dengizek et al
(2016)
to evaluate the clinical and biochemical
(oxidative stress and pro-inflammatory
mediators) effects of the gaseous
ozone use accompanied by scaling and
root planning (SRP) in periodontal
treatment.
The findings of this study indicate that SRP plus gaseous ozone
versus SRP alone does not correlate to a significant
improvement in periodontal recovery.

47. Ozone toxicity:
• Ozone inhalation can be toxic to the pulmonary system and other organs.
Complications caused by ozone therapy are infrequent at 0.0007 per application.
• Known side-effects are epiphora, upper respiratory irritation, rhinitis, cough,
headache, occasional nausea, vomiting, shortness of breath, blood vessel
swelling, poor circulation, heart problems and at a times stroke.
• Because of ozone's high oxidative power, all materials that come in contact with
the gas must be ozone resistant, such as glass, silicon, and Teflon.
• However, in the event of ozone intoxication, the patient must be placed in the
supine position, and treated with vitamin E and n- acetylcysteine.

48. Hyperbaric oxygen therapy:
• Hyperbaric Oxygen Therapy (HBOT) is a method of administering pure oxygen at greater
than atmospheric pressure to a patient in order to improve or correct conditions.
DURATION
• Average duration of therapy is 60 to 90 minutes.
• Number of therapies may vary from
3-5 for acute conditions,
25-30 for non healing wounds,
50-60 for radiation illnesses.

49. • HBO2 therapy in periodontitis patients - 0.25 Mpa or 2.5 ATA pure oxygen
OD for 90 minutes with an air break or 10 minutes in middle of session.
pure O2 - 45 minutes
air 10 minutes
pure O2 - 45 minutes
In total 10 sessions are given.

50. Mechanism of action in periodontitis:
• HBOT showed to increase oxygen distribution at the base of the pocket which is deleterious to
periodontal pathogens, particularly to the anaerobic microorganisms.
• HBO 2 increases generation of oxygen free radicals, which oxidize proteins and membrane lipids,
damage deoxyribonucleic acid and inhibit bacterial metabolic functions.
• It also facilitates the oxygen-dependent peroxidase system by which leukocytes kill bacteria.
HBO 2 also improves the oxygen-dependent transport of certain antibiotics across bacterial cell
walls. In this way HBOT results in inhibition of bacterial growth.
• HBO 2 also promotes fibroblast replication and collagen formation while the patient is in the
hyperbaric chamber. It also increases bactericidal function of leukocytes. HBOT also improve
gingival microcirculation and increase gingival blood flow.

51. Chen et al2002 HBO2 had beneficial therapeutic effects on severe periodontitis.
HBO2 therapy combined with scaling and root planing was the most beneficial
in the treatment of periodontitis.
Chen et al 2003 HBO had good therapeutic effects.
Guo et al 2004 The hyperbaric oxygen therapy combined with supragingival and subgingival
scaling therapy had synergistic action on periodontitis.
Signoretto et al 2007 HBO may represent a useful aid, especially in combination with SRP.
Chen et al 2012 HBO2 therapy combined with scaling and root planing was the most beneficial
in the treatment of AgP.
Wandhawa et al -
2017
HBOT can be beneficial as an adjunctive therapy of chronic
periodontitis when combined with SRP, and that 8 sessions of HBOT is sufficient
for the purpose.

52. Complications:
• Ocular.
• Barotraumatic lesions of
middle ear, inner ear,
nasal sinus, lungs and
teeth.
• Oxygen toxicity in central
nervous system causing
generalized convulsion
(Paul Bert effect) and in
lung causes (Lorraine
Smith effect) occasional
dry cough and burning
substernal sensations.
• Prolonged
hyperoxygenation causes
alveolar exudation and
edema.
Contraindications:
• Untreated tension pneumothorax.
• Concurrent administration of certain medications like. 1.
Bleomycin - Causes interstitial pneumonia. 2. Cisplatin -
Causes impaired wound healing. 3. Doxorubicin - Causes
cardiotoxicity. 4. Disulfiram - Blocks superoxide dismutase,
which is protective against oxygen toxicity. 5. Sulfamylon -
Causes impaired wound healing.
• Upper respiratory tract infection, chronic pulmonary
obstructive disease, congenital spherocytosis, eustachian
tube dysfunction, asthma, pregnancy, claustrophobia,
seizure disorder, hyperthermia.

53. H2O2 photolysis:
• a novel antimicrobial technique, in which hydroxyl radicals generated by
hydrogen peroxide (H2O2) photolysis act as the active ingredient releasing
hydrogen radicals that possess strong oxidative effects.
• Concerning the safety of H2O2 photolysis treatment, the Food and Drug
Administration of the United States considers the application of 3% H2O2
to oral mucosa “acceptable”25, and light at 405 nm is within the range of
visible light.

54. • Kanno et al in 2017 evaluated the clinical efficacy of hydrogen peroxide
(H2O2) photolysis-based antimicrobial chemotherapy adjunctively
performed with root debridement (RD) for moderate to severe
periodontitis in a randomized controlled trial and showed signicant
differences in PD reduction. They suggested that H2O2 photolysis
treatment can be used as a novel adjunctive antimicrobial chemotherapy
for non-surgical periodontal treatment.

55. Prebiotics:
• SELECTIVELY FERMENTED INGREDIENT
THAT ALLOWS SPECIFIC CHANGES BOTH
IN COMPOSITION OR ACTIVITY OF
GASTROINTESTINAL MICROFLORA THAT
CONFERS BENEFITS UPON HOST WELL
BEING
• Inulin, fructo-oligosacharides,galacto-
oligosacharides and lactulose.
• Prebiotics: 1. short chain(oligofructose)
2.long chain(inulin)
3. full-term
prebiotics(oligofructose-enriched inulin)

56. Probiotics:
• According to the World Health Organization in113, probiotics are defined as live cultures
of microorganisms which, when administered in adequate amounts, confer a health
benefit on the host.
• Probiotics have been delivered as yogurt drinks, lozenges, or slowly dissolving tablets,
chewable tablets, chewing gum, oil drops, and as a toothpaste, mouthrinse, and
toothbrush‐cleaning formulation.
• Doses have ranged from 106to 109 and probiotic strains have included various
Streptococcus, Lactobacillus, Bacillus, and Bifidobacterium strains. While a systematic
review (Goldenberg, 2015) found that 106to 109 colony forming units per day can be used
to prevent antibiotic‐associated diarrhea, there are no guidelines on the concentration or
probiotic strain that should be used for optimal effects in dentistry.

57. Mechanism of action

58. Guided pocket recolonization:
• Teughels et al reported that the subgingival application of a bacterial
mixture including Streptococcus sanguinis, Streptococcus salivarius (S.
salivarius), and Streptococcus mitis after scaling and root planing
significantly suppressed the re-colonization of Porphyromonas gulae
(canine P. gingivalis) and P.intermedia in a beagle dog model.
• This novel approach of Guided Pocket Recolonization may provide a
valuable addition or alternative to the armamentarium of treatment
options for periodontitis

59. systematic
review
Conclusion:
Mastubara 2016 Oral administration of probiotics is a safe and effective adjunct to conventional mechanical
treatment (scaling) in the management of periodontitis, specially the chronic disease entity.
Their adjunctive use is likely to improve disease indices and reduce the need for antibiotics.
Cabezas- 2016 the findings of this meta-analysis seem to support the adjunctive use of L. reuteri to SRP in CP
treatment at short-term, especially in deep pockets. Heterogeneity and limited available data
may reduce the impact of these conclusions. Future long-term RCTs evaluating the clinical
efficacy of adjunctive probiotics to SRP are needed.
Jayaram et al 2016 Stated that it is difficult to conclude whether probiotics offer any clinical benefit in the treatment
of periodontal disease. Most studies show a limited and temporary improvement in periodontal
parameters when probiotics are given. Well-designed clinical studies with larger sample sizes
and long-term follow-ups are required. The possibility of administering a booster dose for better
long-term results may also be considered.
Akram et al - 2019 The outcomes of this review show weak evidence to support the use of probiotics in reducing
inflammatory periodontal parameters in gingivitis. Significant heterogeneity and limited
available data may reduce the impact of these conclusions.

60. Systematic
review
conclusion
Barboza et al -2020 The results of the analyzed studies using probiotics in experimental gingivitis showed a slight
improvement in clinical parameters. The GCF volume significantly decreased in the presence of probiotics
in experimental gingivitis compared to the placebo group. The results indicated that the positive effect of
probiotics were due to the modulation of the host response, not the anti-plaque effect. However, the
available evidence presented heterogeneity between the type of study, type of probiotic, dosage,
administration method, and non-brushing period. Therefore, randomized clinical trials are needed to
elucidate the mechanisms of probiotic action and develop better delivery systems.
Gou et al- 2020 the adjunctive use of probiotics seem to achieve short-term clinical benefits in the treatment of
periodontitis. Conclusions must be treated with caution because of high heterogeneity among included
studies and future long-term RCTs are needed to testify the clinical application value of probiotics.
Ho et al- 2020 Heterogenous evidence implied a long-term clinical benefit of probiotics as an adjunct to NSPT.
Outcomes may be impacted by baseline disease severity. Limited microbiological and immunological data
precluded any conclusive findings. Current evidence is insufficient to formulate clinical
recommendations.
Soler et al- 2020 probiotics may provide an additional benefit to manual debridement in chronic periodontitis. More
studies are required on dose, route of administration and strains of probiotics used.

61. Nisin-based probiotics: Lactobacillus lacti
• Recently, 2 studies(Kajwadkar et al 2017 and Shin et al 2015) examined the
effects of a highly purified form of nisin on oral salivary‐derived biofilms
and planktonic forms of oral gram‐positive and gram‐negative oral
bacteria, including Porphyromonas gingivalis, Prevotella intermedia, A.
actinomycetemcomytans, Treponema denticola, and Enterococcus faecalis.
• Nisin inhibited the planktonic growth of these pathogenic bacteria
significantly at concentrations ranging from 2.5 to 50 μg/ml, and the
inhibitory effects increased with increasing concentrations of nisin up to
200 μg/ml.
• studies support the significant potential for using the probiotic L. lactis and
nisin as a therapeutic for periodontal disease and for promoting a healthy
oral microbiome.

62. Predator therapy: Bdellovibrio bacteriovorus
• Van Essche et al. reported that strain B. bacteriovorus (HD100) could attack and
significantly reduce A. actinomycetemcomitans
• B. bacteriovorus is able to tolerate microaerophilic conditions and that in
anaerobiosis it cannot exert its predatory capacity. Such evidence could lead to its
use as an agent to prevent recolonization of the periodontal pocket following
therapy. (Patini et al 2019)
• Silva et al 2019 evaluated the effects of topical administration of Bdellovibrio
bacteriovorus HD100 on experimental periodontitis (EP) in rats and concluded
that topical use of B. bacteriovorus HD100 promotes a protective effect against
alveolar bone loss and CTAL in rats with EP.

63. Antibiotics:

65. Modulation of
inflammation:

66. Specialised pro resolving lipid mediators:
• Specialized pro-resolution
lipid mediators (SPMs)
comprise several
endogenous mediators such
as lipoxins, resolvins,
protectins, and maresins

67. Prevention of P.gingivalis induced periodontitis by topical application of resolvins was evaluated in a
6 week experiment by Hasturk .et al. Significant progression of periodontal disease, including bone
and attachment loss, was observed in the placebo group. Resolvin E1 application prevented the
onset and progression of periodontal disease in experiment group.
In another study by Hasturk H. ,periodontitis was induced with ligature and P. gingivalis in 39 animals
for a 6 -weeks period. local RvE1 application reversed the inflammatory changes including
inflammatory cell infiltration and osteoclastic activity induced by P. gingivalis.
In a pilot trial by ElSharkawy et al. 2010, 80 subjects with moderate to severe periodontitis were
treated with either scaling and root planing followed by a regimen of 900mg of EPA/DHA plus 81mg
aspirin daily for 6 months Addition of the resolvin generating dietary supplement to standard
periodontal therapy provided an added benefit reducing pocket depth and increasing clinical
attachment and providing measurable reductions in inflammatory mediators in saliva.

68. In another randomized controlled trial, Naqvi et al. compared the effect of DHA
supplementation and low-dose aspirin (test group) with the daily consumption of
placebo (control group) in patients with moderate periodontitis who did not
receive any SRP for 3 months. The authors concluded that the test group
presented with significantly decreased mean pocket depth and gingival index, in
comparison to the control group.
Elkhouli et al. evaluated the additional benefit of a 6-month daily PUFA
supplementation and low-dose aspirin in conjunction with regenerative therapy in
class II furcation defects. Apart from the improvement in clinical parameters, the
experimental protocol achieved a host modulatory effect reflected by a significant
reduction in the levels of proinflammatory markers, such as IL-1b, in the gingival
crevicular fluid.

69. Statins:

70. Mundy et al. in 1999 tested the effects of more than 30,000 compounds on bone formation. They found that
the addition of statins to neonatal murine calvarial bone in organ culture increased new bone formation by two-
to three-fold.
The studies conducted by Low and Al-Qawasmi in 2003 showed that the relationship between osteoprotegerin
(OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) will affect the root resorption. Given that
SMV increases OPG to RANKL ratio in periodontal tissues, it can be a factor in preventing root resorption.
Paula et al. in 2010 did a study to evaluate the effect of ATS on alveolar bone loss induced in Wistar rats. A
significant increase in radiographic density was seen in rats receiving ATS when compared to the control group.
This showed that ATS caused reduction in alveolar bone loss.
Pradeep and Thorat in 2010 investigated the effectiveness of locally delivered SMV, 1.2 mg to improve clinical
parameters and enhance bone formation. This study reported a greater decrease in gingival index and probing
depth and more clinical attachment level gain with significant bone fill at sites treated with scaling and root
planing and locally delivered SMV in patients with chronic periodontitis.

71. Systematic reviews
Estanislau et al in 2019 stated that although we found biological mechanisms and clinical results that
show lower alveolar bone loss and reduction of clinical signs of inflammation, further studies are needed
to evaluate the clinical applicability of statins in the routine treatment of chronic periodontitis.
Ambrosio et al in a systematic review in 2018 evaluated if adjunctive local delivery of statins is more
effective than SRP alone. Local statins may offer additional clinical benefits to SRP, even in smokers and
diabetics.
Mauricio et al in 2017 concluded that the collective evidence emerging from this systematic review and
meta-analysis may support the use of locally applied statins as adjuncts to SRP in CP treatment, based on
being an easy, low-cost alternative, with lesser adverse effects on bacterial resistance.

72. Antioxidants:
• Those substances which when present at low concentrations
compared to those of an oxidisable substrate, will significantly delay
or inhibit oxidation of that substrate” - Halliwell & Gutteridge (1989).
Antioxidants can act by
1. Scavenging the species that initiate peroxidation
2. Quenching singlet oxygen
3. Chelating metals
4. Breaking free radical chains
5. Reducing the concentration of oxygen
The protective or destructive effect of PMN could be associated to the
antioxidant capacity of tissues in an oxidative stress condition.

73. mode of action examples
Preventative
antioxidants
Enzymes: superoxide dismutase enzymes (1, 2 and 3),
catalase, glutathione peroxidase, DNA repair enzymes,
e.g. poly(ADP-ribose) polymerase, others.
Metal ion sequestrators: albumin, lactoferrin,
transferrin, haptoglobin, ceruloplasmin, hemopexin,
carotenoids, superoxide dismutase, catalase,
glutathione peroxidase, glutathione reductase, uric
acid, polyphenolic flavenoids
Scavenging (chain
breaking)antioxida
nts
Ascorbate (vitamin C), carotenoids (including retinol –
vitamin A), uric acid, α-tocopherol (vit E), polyphenols
(flavenoids), bilirubin, albumin, ubiquinone (reduced
form), reduced glutathione and other thiols (free or
protein bound)

74. • Muniz et al in 2016 in a systematic review assessed the effects of the
complimentary use of antioxidant agents to periodontal therapy in terms
of oxidative stress/antioxidants and suggested that use of an antioxidant,
complimentary treatment for periodontal disease has the potential to
improve periodontal clinical parameters.
• However, the impact of the combination of periodontal therapy with
antioxidants in terms of antioxidant/oxidative stress parameters requires
further investigation

75. Anti-cytokine therapy:
TNFα antagonist
1. Adalimumab
2. Golimubab
3. Infliximab
4. Entanercep
Anticytokine agents
1. Anakinra
2. Canakinumab
3. AMG714
4. AIN457
Inhibitor of cytokines from
the tumor necrosis factor
superfamily
Atacicep

76. • In the context of periodontal wound healing, some anti-cytokine
treatments have been tested in animal models. Animal studies have
shown that the systemic administration of recombinant interleukin-11
reduced bone loss in a dog model of periodontitis, and etanercept
reduced inflammation, tissue injury and neutrophil infiltration in a rat
model of experimental periodontitis.
• To present day knowledge, no study using anti-cytokine treatment has
been performed in human in the context of periodontitis only.

77. Tereparatide:
• Teriparatide, a biosynthetic human parathyroid hormone, which consists of
the first 34 amino acids of parathyroid hormone, is an anabolic agent.
• Administration – 1 inj OD – 20 µg/day
• Adverse effects: Blackbox warning from FDA due to adverse effect of
Osteosarcoma

78. Mechanism of action:
• Teriparatide and PTH mediate their biological effects via specific, G-protein-
dependent, highaffinity membrane cell-surface receptors.
• These receptors are expressed on osteoblasts and renal tubular cells; both
these molecules bind to the receptors with the same affinity and exert the
same physiological effects on bone and kidney.
• Binding of ligand induces a cascade that activates protein kinase-1, cyclic
adenosine monophosphate, protein kinase-C and phospholipase-C, which
results into an increase in the number of active osteoblasts, a decrease in
osteoblast apoptosis and probably, recruitment of bone lining cells as newly
formed osteoblasts, thereby increasing bone strength.

80. Bisphosphonates:
• Similar to pyrophosphate
• Generations –
1st generation: Etidronate , clodronate
2nd generation: Pamidronate, Alendronate
3rd gen: Risedronate, Zoledronate

81. Mechanism of action

82. • Akram et al in a systematic review in 2017 assessed the efficacy of
bisphosphonate therapy as an adjunct to scaling and root planing (SRP)
in the management of periodontitis and concluded that adjunctive
bisphosphonate therapy appears to be effective in managing
periodontitis, however, due to the potential risk of osteonecrosis of the
jaws and short‐term follow‐up of the studies, their clinical application is
debatable.

83. Gene therapy:
• Gene therapy is a technique utilized to deliver plasmid DNA encoding the
protein of interest into cells/tissues either directly or via gene delivery
vehicles or vectors.
• In vivo and ex-vivo techniques are the two different approaches by which
gene therapy can be performed. In the former, the gene of interest is
directly applied either alone or in a vector into the anatomical site,
whereas, in the latter approach, the gene transfer into cells takes place
outside the body and then the cells are subsequently transplanted into the
site of interest.

84. Studies:
• A unique advantage of gene therapy is the possibility of delivering more
than one regenerative factor by employing two or more DNAs. This
combinatorial approach has showed significant regenerative potential
compared to individual gene delivery .
• Jin et al (2003): direct in vivo gene transfer of PDGF-B stimulated tissue
regeneration in large periodontal defects
• Anusaksathien et al (2006): ex vivo investigation, showed that the
expression of PDGF genes was prolonged for up to 10 days in gingival
wounds

85. • Franceschi et al (2005) investigated in vitro and in vivo Ad gene transfer of BMP-
7 for bone formation
• A study by Zhaang et al in 2007 used chitosan based scaffolds in the delivery of
PDGF in an in vivo model and demonstrated the potential of porous chitosan in
periodontal regeneration.
• in vivo study by Moutsatos et al demonstrated the direct application of BMP-2
with the efficacy of engineered mesenchymal stem cells (MSCs) as a BMP-2
delivery unit. Significant increase in bone regeneration was observed in the
stem cell based gene delivery group compared to controls

86. Nanotechnology:
• The recent nanotechnology innovations are increasingly providing a suitable
solution for the treatment of many dental disorders including periodontal disease.
• Nanorobotics- dentifrobots.
• Pinon-Segundo et al - Triclosan loaded nanoparticles - reduced gingival
inflammation in dogs.
• Nano metals- silver ,copper, zinc
• Anti- nanobacterial mouthwashes: BPN, gallium nitrate and SNP
• Dendrimers
• Liposomes
• Nanobubbles

87. DRUG DELIVERY MODE ROLE REFERENCES
NANOPARTICLES Potential carrier system for the delivery of active
substances to the periodontal pocket
Aminu et al., 2013
Triclosan-nanoparticles could help decrease
gingival inflammation
Piñón-Segundo et al., 2005
Minocycline-loaded nanoparticles could
significantly decrease symptoms of periodontitis
Yao et al., 2014
Calcium and zincloaded bioactive and
cytocompatible nanoparticles represent a
promising tool for therapeutic approach in
periodontal regeneration
Osorio et al., 2016
Various investigated nanoparticulate drug delivery
systems and their roles in periodontal disease
therapy.

88. DRUG DELIVERY MODE ROLE REFERENCES
NANOGELS Nanogels of cholesterolbearing pullulan modified
with amino groups (CHPNH2) were utilized as a
career to introduce QDs into PDL cells
Fukui et al., 2007
CHPNH2-QD nanoparticles are useful for further
characterization of PDL cells and investigation of
regenerative processes of periodontium
Fukui et al., 2007
NANOCOMPOSITES Thin layer of nanocomposites has been used to
provide coating on tooth surface, which strongly
reduced biofilm formation
Hannig et al., 2007
Nanocomposite hydrogels were synthesized as
model systems and it offers flexibility for local
placement of drugs in the treatment of
periodontal disease
Bako et al., 2008
Dental bioactive nanocomposite composed of 2-
methacryloyloxyethyl phosphoryl choline and
dimethylamino hexadecyl methacrylate is
promising for Class V restorations to inhibit
periodontal pathogens, combat periodontitis and
protect the periodontium
Wang et al - 2016

89. DRUG DELIVERY
MODE
ROLE REFERENCES
NANOFIBERS Poly-ε-caprolactone (PCL) nanofibers containing metronidazole
showed prolonged sustained drug release for at least 19 days and
can be used as a retentive, locally controlled delivery system for
metronidazole in periodontal diseases treatment
Chaturvedi et al., 2012;
Zamani et al., 2010
Low-dose controlledrelease PCL nanofibers containing doxycycline
showed sustained drug release and can be used as a retentive
controlled delivery system for the treatment of periodontal
diseases
Chaturvedi et al., 2013
Drug loaded hyaluronic acid-polyvinyl alcohol nanofiber patch
presented controlled release behavior with good mucoadhesive
strength. The in vivo studies confirmed the maintenance of
minimum inhibitory concentration over an extended period in
addition to a significant anti-inflammatory effect, which suggested
the formulation’s role as an intra-periodontal pocket drug delivery
system
Joshi et al 2015
Resveratrol-loaded PCL nanofibers improved low solubility and
stability of resveratrol and it can supply the drug for treatment of
periodontal disease in the periodontal pocket even longer due to
sustained release and low gingival fluid flow
Zupančič et al., 2015

90. Hyaluronic acid:
• Hyaluronic acid (HA) is a
naturally occurring linear
polysaccharide of the
extracellular matrix of
connective tissue, synovial
fluid, and other tissues.

91. Pistorius Alixander evaluated the efficacy of topical application of HA for treatment of gingivitis and
found that topical application of HA containing preparation was potentially useful adjunct in the
therapy of gingivitis.
Gengigel®(Ricerfarma S.r.l., Milano, Italy) contains high molecular weight fractions of HA in a gel
formulation with 0.2% concentration for its effect in the treatment of plaque-induced gingivitis as
an adjunct to SRP. The adjunctive use of 0.8% Hyaluronan after thorough mechanical debridement
potentially has major clinical benefits in terms of improved healing after non-surgical therapy.
Johannsen et al. conducted a split mouth design study to evaluate the adjunctive effect of local
application of 0.8% Hyaluronan gel to SRP in the treatment of chronic periodontitis. They found a
significant reduction in bleeding on probing (BOP) scores and PD in SRP + hyaluronan gel group as
compared to SRP group
Studies:

92. Gontiya et al. investigated the clinical and histological outcomes of local subgingival application of
0.2% HA gel as an adjunct to SRP in chronic periodontitis patients. They concluded that subgingival
placement of 0.2% HA gel along with SRP provides a significant improvement in gingival
parameters, but no additional benefits were found in periodontal parameters. Histologically,
experimental sites showed reduced inflammatory infiltrates, but the results were not statistically
significant.
Bert et al through a systematic review in 2015 evaluated the effect of hyaluronan (HY) application
as monotherapy or as adjunct to non‐surgical and/or surgical periodontal therapy. They concluded
that Hyaluronan application as adjunct to non‐surgical and surgical periodontal treatment seems
to have a beneficial, generally moderate, effect on surrogate outcome variables of periodontal
inflammation, i.e., BoP and residual PD, and appears to be safe. The large heterogeneity of
included studies, does not allow recommendations on the mode of application or effect size of HY
as adjunct to non‐surgical and surgical periodontal treatment.

93. Naturoceutics/Phytotherapy:
Author Product Conclusion
Bodet et al Licorice extract Potential candidate for the development of a new therapy to
prevent and/or treat periodontitis-associated tissue
destruction.
Tanaka et al Eucalyptus-extract Chewing gum may reduce oral malodor by decreasing the
accumulation of tongue coating.
Sofrata et al Miswak Strong antibacterial effect against oral microorganisms
associated with periodontitis and caries.
Shimazaki et al Lactic acid Routine intake of foods may have a beneficial effect on
periodontal disease.

94. Harokopakis et al Elder flower extract Anti-inflammatory properties
Houde et al Proanthocyanidins Potent antioxidant properties
Abraham et al Triphala Strong inhibitory activity on PMN-type MMPs
involved in the extracellular matrix (ECM)
degradation during periodontitis
Chandra et al Lycopene Treatment modality in gingivitis
Nelson Wood et al Tomato Monthly intake seems to have positive relationship in periodontal
patients
Gebaraa et al Propolis Subgingival irrigation as an adjuvant to periodontal treatment
was more effective than conventional treatment both by clinical
and microbiological parameters.
Soukoulis et al Tea Tree Oil Anti-inflammatory properties
Kushiyama et al Green tea Inverse association between the intake and periodontal disease

95. Coastal pine trees – Pycnogenol-chewing gum for 14 days: reduction in gingival
inflammation
Coenzyme Q10 - modulator of periodontal disease.
Craneberry containing products - prevent attachment of pathogens to host tissues..
Cutando et al Melatonin Plays a role in protecting the oral cavity from
tissue damage that is due to oxidative stress,
and it may contribute to the regeneration of
alveolar bone through the stimulation of
type I collagen fiber production and the
modulation of osteoblastic and osteoclastic
activity

96. Tri-immunophasic therapy: William
Hoisington
• TIP periodontal therapy methods are:
• 1. Bone One Session Treatment (stretch flap technique)
• 2. Controlling occlusal Forces
• 3. Oral Hygiene reinforcement with adjuvant modalities ( Perio-aid)
• 4. Life Style modification
• 5. Enhancing nutrition and Exercise.

97. Conclusion:
Good supragingival plaque control in
combination with mechanical instrumentation
and supportive periodontal therapy can maintain
periodontal health for more than 20 yrs and this
can be considered as ‘gold standard ‘of
periodontal care.
Alternative approaches to this gold standard
should be easy to use, affordable, patient
friendly, and accessible to large mass of people
spread over countries and continents

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