A REVIEW ON RECENT ADVANCEMENTS IN TREATMENT OF …

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940

Sivadasu et al. World Journal of Pharmacy and Pharmaceutical Sciences

A REVIEW ON RECENT ADVANCEMENTS IN TREATMENT OF

PERIODONTITIS

Praveen Sivadasu*, Boppudi Bindu Sri, Gorre Asha, Bhukya Chandana,

Abdul Safiya Naseema, Mamillapalli Sneha Latha and Padmalatha K.

Vijaya Institute of Pharmaceutical Science for Women, Enikepadu, Vijayawada-521 108

Krishna District Andhra Pradesh, India.

ABSTRACT

Periodontitis is considered as a chronic localized inflammatory disease

related to teeth and its supporting structures. The disease is initiated by

subgingival periopathogenic bacteria followed by inflammation of

gums, degeneration of the periodontal ligament and alveolar bone loss.

In this outlook scaling and root planing was considered as the basic

treatment approaches to treat periodontitis which have severe

shortcomings like unable to reach the deep pockets and inhibiting the

progression of the bacterial infection. In order to overcome the

shortcomings of scaling and root planing various novel preventive

treatment modalities like host modulation, anti-microbial therapy, and

full mouth disinfection can be used as either adjunctive treatments or

stand-alone treatment options. These novel treatment modalities had

shown significant improvement in blocking the growth of bacteria when compared with the

traditional approaches of treatment. This review will cover an update on the past and the

recent advancements in the various treatment modalities for periodontal diseases.

KEYWORDS: Periodontitis; Periodontal therapy; Oral hygiene; Host modulators; Anti-

microbial.

INTRODUCTION

Periodontitis (PDT) disease was known to mankind from ancient times. Physicians and

researchers have established different forms of this disease, clinical symptoms, and the rate at

which disease progression happens.[1-3]

Chronic periodontitis is termed as a progressive

disease where gingival periodontal ligament and alveolar bone will be affected and as a result

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 9, Issue 3, 940-961 Review Article ISSN 2278 – 4357

*Corresponding Author

Praveen Sivadasu

Vijaya Institute of

Pharmaceutical Science for

Women, Enikepadu,

Vijayawada-521 108

Krishna District Andhra

Pradesh, India.

Article Received on

11 January 2020,

Revised on 13 Feb. 2020,

Accepted on 17 Feb. 2020

DOI: 10.20959/wjpps20203-15679


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of this infection, there will be a change in tooth structure leading to alveolar bone

resorption.[4-6]

Periodontitis can be diagnosed by understanding the anatomy of healthy gums. A healthy

gum will be in pink color stippled firmly to the underlying tissue, scalloped at cemento-

enamel junction with a gingival crevice of 1-3 mm without any bleeding and this attached

gingival extends from gingival groove to mucogingival junction by tightly binding to the

underlying bone and resists any kind of injury.[7]

Further, any kind of deviations from this

condition will lead to either gingivitis or periodontitis. Gingivitis is considered as an acute

and a reversible condition where inflammation is restricted to only marginal and surrounding

connective tissue without any loss of attachment. Whereas, periodontitis is considered as a

chronic and irreversible condition which occurs when the inflammation reaches the

periodontal ligament and alveolar bone.[8-10]

The pocket formation between tooth surface and gingiva occurs due to apical displacement of

the epithelium at the junctions which can be termed as a primary indicator for periodontitis.

However, it is known that not all cases of gingivitis will lead to periodontitis. Similarly Loe

et al.[11]

has done a study on the initiation and progression of periodontal disease in the

Srilankan population. From the study, it was evident that 8% of the population had rapid

progression of the disease, while 81% had moderate progression and for 11% of the

population there is no progression of the disease from gingivitis.

Periodontitis is associated with the incidence of coronary heart disease, pneumonia,

rheumatoid arthritis, preterm birth, head and neck squamous cell carcinoma( HNSCC) and

risk of developing lung, kidney, pancreas and hematological cancer.[12]

An understanding of

the latest trends in the treatment options is essential to treat periodontitis.

ETIOLOGY

By the mid-1960s, several researchers had come to the conclusion that initiation and

progression of periodontal disease are caused by the supra and subgingival dental plaque

which is now called the microbial biofilm. The identification and characterization of these

―periodontal pathogens‖ have been a major driving factor of periodontal research for the past

5 decades. Periodontitis is termed as a chronic inflammatory disease, in which severe forms

of the disease are associated with specific bacteria that have colonized the subgingival area

regardless of the host’s protective mechanisms. In recent times focus on the etiology of


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periodontal disease has changed markedly with a emphasis on specific anaerobic

microrganisms like porphyromonas gingivals (p. Gingivalis), tanneralla forsythia, treponema

denticola, aggregatibacter actinomycetemcomitans (previously known as actinobacillus

actinomycetemcomitans), prevotella intermedia, and others including fusobacterium

nucleatum, wolinella recta, and spirochetes as the initiating factors which are also considered

as primary etiologic factors.[13, 14]

Further, in more aggressive (and rare) forms of periodontal

disease microorganisms like aggregatibacter actinomycetemcomitans have been observed. [15,

16] Furthermore, a group of pathogens not typically present in the oral cavity has also been

linked to periodontal diseases, such as enterobacteracea, pseudomonadacea, and

acinetobacter.[17]

SIGNS AND SYMPTOMS[18]

Swollen or puffy gums

Bright red, dusky red or purplish gums

Gums that feel tender when touched

Gums that bleed easily

Gums that pull away from your teeth(recede), making your teeth look longer than normal

New spaces developing between your teeth

Pus between your teeth and gums

Painful chewing

A change in the way your teeth fit together when you bite

Halitosis, or bad breath, and a persistent metallic taste in the mouth

Deep pockets between the teeth and the gums (pockets are sites where the attachment has

been gradually destroyed by collagen-destroying enzymes, known as collagenases).

Loose teeth, in the later stages (though this may occur for other reasons, as well)People

should realize gingival inflammation and bone destruction are largely painless. Hence,

people may wrongly assume painless bleeding after teeth cleaning is insignificant,

although this may be a symptom of progressing periodontitis in that person.

PATHOPHYSIOLOGY

Besides dental caries, periodontal disease is considered as one of the most prevalent diseases

in the world. The milder, reversible form of the disease, gingivitis, comprises inflammation

of the gingival tissue. In disease-susceptible individuals, gingivitis may progress to

periodontitis, which is a chronic inflammatory state of the gingiva causing destruction of

https://en.wikipedia.org/wiki/Halitosis

https://en.wikipedia.org/wiki/Gingival_and_periodontal_pockets

https://en.wikipedia.org/wiki/Collagen

https://en.wikipedia.org/wiki/Collagenases

https://en.wikipedia.org/wiki/Occlusal_trauma


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connective tissue as well as of alveolar bone resulting in reduced support for the teeth and

ultimately tooth loss as shown in Fig. 1.[19-21]

The pathogenesis of periodontitis has been

gradually elucidated during the latter half of the 20th century. In the 1960s and 1970s,

research on humans and animals showed that bacteria play a critical role in initiating

gingivitis and periodontitis.[22]

Leading up to the 1980s, there were further advances within

the field and the pivotal role of the host inflammatory response in disease progression began

to emerge.[23]

Further, systemic conditions and environmental factors such as smoking were

also shown to greatly affect the disease onset and progress.[24]

For over a decade now, the

concept of periodontitis has been considered to be a complex interaction between the

microbial challenge and the host response, which alters the physiology of both connective

tissue and the bone as depicted in Fig. 2.[25]

Fig 1: Characteristics of periodontitis.


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Fig. 2. Schematic overview of the pathogenesis of periodontitis.

CURRENT TREATMENT APPROACHES OF PERIODONTITIS

The initiation of periodontitis is generally caused by bacterial infections. Further, treating

periodontitis is considered a great challenge due to the formation of bacterial biofilm which is

hugely resistant to antimicrobials and host response modulators. Bacteria continue to remain

in the oral cavity even after the removal.[26]

Various approaches can be used to treat

periodontitis like Surgical, non-surgical and pharmacological therapies which are explained

in detail in the below section.

Nonsurgical treatments

Scaling

Scaling removes tartar and bacteria from your tooth surfaces and beneath your gums. It may

be performed using instruments, a laser or an ultrasonic device.[27]

Root planing

Root planing smoothes the root surfaces and inhibit the further build-up of tartar and bacteria,

and removes bacterial by-products that contribute to inflammation and delay healing or

reattachment of the gum to the tooth surfaces as shown in Fig 3.[28]


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Fig. 3: Root planning.

Surgical treatments

Surgical approach to treat periodontitis is required when the progress of the infection is way

too advanced and different surgical options were discussed below in detail.

Flap surgery (pocket reduction surgery)

Flap surgery will be initiated by making a tiny incision on the gum so that it can be lifted by

exposing the roots. Further, more effective scaling and root planing can be performed as

periodontitis causes considerable loss of bone as shown in Fig 4. Post scaling and root

planing the gum tissue is sutured back in place and proper care should be taken to keep the

gum tissue healthy and to avoid relapse of bacterial infection.[29]

Fig. 4: Pictorial view of flap surgery.


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Soft tissue grafts

Gum tissue damage in periodontitis leads to changes in the gumline which should be

replaced. A typical procedure involves removing a small segment of tissue either from the

upper portion of the mouth or from a donor and attached to the affected site as shown in Fig

5. Further, this tissue grafts can reduce the recession of gums, coverage of exposed roots and

gives a pleasing appearance to the teeth.[30]

Fig. 5: Pictorial view of a soft tissue graft.

Bone grafting

A typical bone grafting procedure will be performed when the bacterial infection has

completely destroyed the bone surrounding the teeth. Further, the procedure involves placing

a graft consisting of either bone from the patient or from a donor or it can also be of synthetic

origin as depicted in Fig 6. The placed graft gives strength to hold the teeth in place and

serves as a platform for the regrowth of damaged bone.[31]

Fig. 6: Pictorial representation of a bone graft.


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Guided tissue regeneration

Tissue regeneration technique is employed to treat periodontitis when the bacterial infection

is in an advanced stage. A typical procedure involves placing a piece of biocompatible fabric

between damaged bone and teeth. The grafted material will prevent the entry of unwanted

tissues and allow the damaged bone to grow back.[32]

Similarly to treat the infected bone a

special gel containing tissue simulating proteins is applied to the infected root.[33]

Pharmacological therapies

The systemic antimicrobial approach in the treatment of periodontitis

Traditional antimicrobial approach to treat periodontitis involves mechanical debridement of

root surfaces to disrupt the formed bacterial biofilm.[34]

Further, this approach blocks the only

progression of biofilm attachment but if the disease is caused by invasive periopathogenic

bacteria like (Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis or

Prevotella intermedia) mechanical debridement is not sufficient to treat the disease. In order

to overcome the above drawback systemic anti-microbial approach can be used. Wherein, the

systemic anti-microbial approach includes the administration of drugs like amoxicillin,

metronidazole, tetracyclines (doxycycline), clindamycin, azithromycin, clarithromycin and

ciprofloxacin (Table 1) as an adjunct to mechanical debridement. As reported earlier

periodontal lesions to occur due to a mixture of pathogenic bacteria where a combination of

prescribed antibiotics would be necessary.[35]

Further, when a periodontal infection is caused

by enteric rods, pseudomonas or A. actinomycetemcomitans a combination of metronidazole

and ciprofloxacin can be used and in another case, a combination of amoxicillin and

clavulanic acid can also be used to treat periodontal infections.[36]

Research data also

suggested that given antibiotics are within the therapeutic range to treat the infection

effectively. However, disadvantages include inadequate drug concentration in the periodontal

pocket, a rapid decline of the plasma antibiotic concentration to sub-therapeutic levels and

high peak plasma concentration that might be associated with side effects that can be

overcome by formulating novel micro and nano-drug carriers.


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Table 1: Antibiotics used in the treatment of periodontal diseases.

Antibiotics Dosage in adult periodontitis References

Metronidazole 500 mg three times daily [37]

Clindamycin 150 mg three times daily for eight days [38]

Penicillins (amoxicillin) 250-500 mg three times daily [39]

Tetracyclines (doxycycline) 200 mg initially, 100 mg for seven days [40]

Azithromycin 250-500 mg for three days [41]

Claritromycin 500 mg 2 x daily for three days [41]

Fluoroquinolones (ciprofloxacin) 500 mg twice a day for eight days [42]

Amoxicillin/Metronidazole 250-375 mg of each 3 x daily for 8 days [43]

Metronidazole/Ciprofloxacin 250 mg of each 2 x daily for 8 days [44]

Amoxicillin + clavulanic

acid/metronidazole 250 mg 3 x daily for 8 days

[45]

The local antimicrobial approach in the treatment of periodontitis

Delivery devices intended to cure periodontal infections locally are fibers, strips, films,

injectable gels, micro/nanoparticulate systems or vesicular systems. Further, various drugs

like tetracycline-hydrochloride, doxycycline, minocycline, metronidazole, chlorhexidine, and

ofloxacin were used to load in the above-mentioned carriers to treat periodontal infections.[46]

Some of the commercially available local delivery systems for periodontal treatment and their

characteristics are given in Table 2.

Table 2: Commercially available local delivery systems for periodontal treatment

Commercial

product

Local drug

delivery system

Therapeutic

compound Applications Advantages

ActisiteTM

Nonabsorbable

Fiber

25% tetracycline

HCl

1 application

7-day treatment

chairside

Bactericidal High

levels of tetracycline in

GCF

AtridoxTM

Gel

10% doxycycline

hyclate

1 application 7-day

treatment Chairside

Forms solid implant

Biodegradable

bactericidal

ArestinTM

Microspheres

1mg minocycline

HCl

1 application 14-day

treatment Chairside

Bioadhesive

Biodegradable

Bactericidal

Periocline®

Dentomycin® Gel

2% minocycline

HCl

1 application 14-day

treatment Chairside

Bioadhesive

Biodegradable

bactericidal

Periochip® Thin, solid, chip

2.5 mg

chlorhexidine

digluconate

1 application 7-day

treatment Chairside

Biodegradable

bactericidal

Elyzol® Gel 25% metronidazole

benzoate

2 applications 7-day

treatment Chairside

Biodegradable

bactericidal


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Topical antiseptics

Povidone-iodine

The broad-spectrum antibacterial properties of povidone-iodine are well known in medicine.

This compound is effective against various periodontopathic bacteria and cytomegalovirus

activity (herpes virus implicated in the pathogenesis of periodontitis). Povidone-iodine does

not exhibit adverse side effects such as discoloration of teeth and tongue or change in taste as

seen with the usage of chlorhexidine. It has a low potential for developing resistance and

adverse effects. Further, a solution containing a 10% concentration of povidone-iodine is

considered as an effective concentration for subgingival irrigation. A typical procedure

involves applying the above-said concentration with the help of an endodontic syringe up to 5

min. different researchers have reported a favorable clinical outcome after treating advanced

periodontitis with subgingival povidone-iodine and systemic antibiotics.[47]

Sodium hypochlorite

Sodium hypochlorite has been used as an endodontic irrigant for more than 75 years. Sodium

hypochlorite poses various advantages like broad antimicrobial activity; rapid bactericidal

action; relatively non-toxic; no color or staining; ease of access; and economical. Various

research works suggested that using sodium hypochlorite as a treatment option improved

periodontal histological healing.[48]

Corticosteroids for local application on the periodontium

Corticosteroids are a class of drugs that were used for various biomedical applications

because of their potent anti-inflammatory and immunosuppressant properties.[49]

Topically,

their predominant anti-inflammatory action appears to be on eicosanoid formation.

Corticosteroids stimulate the production of various polypeptides, collectively called

lipocortin that inhibits phospholipase A2 activity. Further, another corticosteroid induced-

complex, vasocortin has been found to inhibit oedema formation. Corticosteroids are thought

to in some ways stabilize lysosomal membranes, thus suppressing the release of lytic

enzymes.[50]

Literature suggested that budesonide which is a new generation corticosteroid

with potent local anti-inflammatory effect could be used in the treatment of periodontal

disease. Further, in vivo studies have shown that inhaled budesonide could not modulate

periodontal breakdown, this might be due to inappropriate formulation and dosage.

Additional studies are needed to estimate the effects of budesonide on the oral mucosa and

the periodontium.[51]

While a topical application of corticosteroids for skin disorders is well


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documented, there is considerably less critical information available for lesions of the oral

mucosa, including periodontal disease. Therefore, there is a need for further research into

therapeutic systems that improve local delivery of corticosteroids to oral mucosa and

periodontium as well as controlled clinical studies in order to evaluate the clinical

effectiveness of these formulations attended for treatment of periodontal lesions.[52]

Host modulatory therapies

Host Modulatory Therapies (HMT) can be used to reduce the progression of infection and

allows to treat the infection and can also be used as preventive agents against the periodontal

infection. In the last two decades, scientists have investigated various host modulating

strategies in both animal and human experimental models and prescribed a set of modulations

like regulation of production of arachidonic acid metabolites; regulation of bone remodeling;

regulation of matrix metalloproteinase (MMPs) activity; regulation of nitric oxide synthase

activity.[53]

Nonsteroidal anti-inflammatory drugs (NSAIDs)

The non-steroidal anti-inflammatory drugs are a group of pharmacological agents that have

been well studied as an inhibitor of the host response in periodontal disease. These agents

have been shown to prevent the formation of arachidonic acid metabolites, especially

prostaglandins which have an important role in the pathogenesis of periodontitis.[54]

In vitro

and in vivo preclinical studies using NSAIDs have suggested their ability to reduce

prostanoid formation by inhibiting COX enzymes.[55]

Biphosphonates

Biphosphonates are the therapeutic agents used to slow down the alveolar bone loss and

increase mineral bone density. In recent times research works have suggested that a

significant clinical improvement was observed. These results encourage the use of

bisphosphonates as adjunctive agents to periodontal therapy. However, additional studies are

further needed in order to evaluate the relative risk-benefit ratio of bisphosphonate

therapy.[56]

Regulation of matrix metalloproteinase activity

Matrix metalloproteinases (MMPs) represent a family of zinc-dependent membrane-bound

and secreted proteolytic enzymes that catalyze the breakdown of proteins in the cell plasma

membrane or within the extracellular matrix.[57]

Deregulation of MMPs activity is required in


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different conditions such as rheumatoid arthritis, tumor cell metastasis, and periodontal

disease.[58]

The ability of anti-microbials like tetracycline and doxycycline to inhibit MMP

activity was first identified in the early 1980s. Tetracyclines block the active enzyme and

inhibit reactive oxygen species involved in the activation of these enzymes.[59]

RECENT ADVANCEMENT IN TREATMENT OF PERIODONTITIS

There are many advancements introduced in the probing system which helps in knowing the

correct measurements of pocket depth and clinical attachment loss. The various

advancements in the treatment of periodontal disease are as follows.

1. Vaccine for the disease.

2. Lasers in the treatment of periodontal disease.

3. Probiotics in the treatment of periodontal disease.

4. Microsurgery for periodontal treatment.

5. Photodynamic therapy in the treatment of periodontal disease.

6. Tissue engineering in the treatment of periodontal disease.

7. Nanotechnology in the treatment of periodontal disease.

8. Newer drugs developed for treating periodontal disease.

9. Ozone therapy in periodontology.

Vaccine for disease

The vaccination process gives immunity to the body by producing antibodies against the

antigens. The vaccination concept for periodontitis was introduced because the origin of the

disease is due to bacteria with some other factors. Vaccination work on three principles 1.

Active immunization in which entire bacteria cells are introduced in a host as an antigen, 2.

Passive immunization in which monoclonal antibodies are introduced in host and 3. Genetic

immunization where the live and viral vaccine is introduced. In the 20th

century, the

periodontal vaccine came into existence with Vancott's vaccine and the Inava endocarp

vaccine. Bacterias like P. Gingivalis, Aggregatibacter actinomycetemcomitan and T.

Forsythia are responsible for periodontal infection. This vaccination process has the potential

to stop the progress of infection and improve quality of life.[60]

Laser in treatment of periodontal disease

Albert Einstein has given the concept of Laser. Nowadays laser is being used for various

purposes in the field of periodontology, like de-epithelialization, incision, curettage, sulcular

debridement frenectomy, second stage implant surgery etc., Laser-Assisted New Attachment


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Procedure (LANAP) with ultrasonic root debridement was done for immediate post-treatment

effects on putative bacterial pathogens in deep human periodontal pockets. A typical

procedure involves selecting 26 systemically-healthy adults with severe periodontitis.

LANAP surgery was performed using, pulsed Nd: YAG laser, with laser energy (4.0W, 150-

µs pulse duration, 20-Hz) directed circumferentially around teeth parallel to root surfaces in a

coronal-apical direction to probing depth. After ultrasonic root debridement and gingival flap

advancement to the alveolar bone crest, a second laser pass (4.0 W, 650-µs pulse duration,

20-Hz) was similarly performed in an apical-coronal direction to thermally initiate a fibrin

clot at the tooth-gingival flap junction. Another laser system SiroLaser Blue has been

introduced that works at three wavelengths that is at 970, 660 and 445nm. This system has

been newly introduced in the United States in September 2018 and promoted by Dr. Smon

Suppelt for its cutting efficiency at 445nm. This is manufactured by Dentsply Sirona. This

system emits blue light at 445nm.[61, 62]

Probiotics in the treatment of periodontitis

At the beginning of the 20th

century, Elie Metchnikoff discovered some useful bacteria that

have a positive effect on health and suggested that these bacteria can help to eliminate

harmful bacteria. Probiotics are defined as ―Live microorganisms that once administered in

adequate amounts confer a health advantage on the host". The mechanism of probiotics is as

follows.

They compete for space and inhibit the pathogenic bacteria or its growth that cause dental

plaque.

Compete for nutrients and inhibit the growth of the pathogen.

They increase the production of IgA antibodies or inhibits the production of pro-

inflammatory cytokines.

All these mechanisms act as antagonists to pathogenic bacteria and reduce tissue

inflammation and destruction. Probiotics are used in the form of tablets, lozenges, capsules,

cheese, yogurt, rinses and liquids.[63]

Golfre et al. in their study used Lactobacillus reuteri

Prodentis as a probiotic to treat patients with peri-implant mucositis or periimplantitis who

already had periodontitis in combination with non-surgical mechanical therapy and found out

that there was a significant improvement in clinical parameters both in mucositis and

periimplantitis around the implant.[64]


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Microsurgery for periodontal treatment

Microsurgery is defined as the surgical procedure done under the microscope for better

visualization and for better healing. In the field of periodontology, microsurgery is being used

for procedures like root coverage procedure, papilla reconstruction, aesthetic implant surgery,

periodontal flap surgery, etc.,[65]

Tibbetts and Shanelec in 1994 used the microsurgical

technique for regeneration and augmentation of periodontal soft tissue. The advantage of this

procedure is better and fast healing with less post-operative pain.[66]

Similarly, Cortellini and

Tonetti in 2007 came with the concept of minimally invasive surgical technique and later

introduced the concept of space provision for regeneration with the modified MIST (M-

MIST). The procedure is done under magnification with microsurgical instruments. Loups or

microscope is being used for the purpose with magnification ranging from 3.5-20. The main

advantage of the procedure is less postoperative pain and better and faster healing.[67]

Photodynamic therapy in the treatment of periodontal disease

Jodelbaner and Von Tappeiner introduced the term photodynamic in 1904. With it’s targeted

action and non-invasive nature this treatment modality has been successfully used for the

treatment of many precancerous and cancerous lesions. A typical procedure involves using

the photosensitizer that gets localized to the site of action and upon illumination, with the

light of wavelength 630-700 nm the photosensitizer turns into the excited state and leads to

two types of reaction Type I and Type II reactions in photodynamic therapy. The Type I

pathway involves reactions that require a transfer of an electron from the photosensitizer

triplet state with the involvement of a substrate to produce radical ions that can react with

oxygen to produce cytotoxic species. In Type II pathway energy transfer takes place from the

photosensitizer triplet, state to the ground state molecular oxygen (triplet) to produce excited

singlet oxygen species, which can lead to oxidation of biological molecules. Birang et al. In

their study found that adjunctive laser therapy or photodynamic therapy showed more

improvement of CAL gain compared to that of SRP alone, which shows that laser and

photodynamic therapy reduces inflammatory mediators like IL-1beta and IL-17 and enhances

the clinical symptoms.[68, 69]

Tissue engineering in the treatment of periodontal disease

Melcher introduced the concept of tissue engineering in the field of periodontology, and he

introduced the cell barrier principle in1976. Due to the introduction of guided tissue

regeneration in periodontology by Nyman and karring in 1982 using the barrier membrane


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has raised the evolution of tissue engineering. Gaubys et al. Studies showed a positive

influence on periodontal tissue complex regeneration by stem cell therapy. Recent

advancement has focused on the development of periodontal ligament attachment around

dental implants to replace lost teeth. Similarly, gene therapy where genes are transferred to

the desired site by means of vector which can be viral like Retrovirus, Lentivirus,

Adenovirus, Adenoassociated virus or non-viral vectors like physical vectors consisting of

Electroporation, Gene gun, Ballistic particle delivery; chemical vectors like Cationic polymer

diethylamino methyl-dextran, Calcium phosphate co-precipitation, Lipid mediated types like

Cationic liposomes, Lipoplexes and as Gene-editing tools like Zinc finger nucleases (ZFNs),

Transcription Activator Like Effector-based Nucleases (TALENS) and Clustered Regularly

Interspaced Short Palindromic Repeats (CRISPR-Cas9) is being used for controlling the

release of growth factor to the defect site so that an appropriate amount of factors are released

at the appropriate time and in the production of pluripotent cells, called induced pluripotent

stem cells. It is also being used to enhance host modulation to resist disease.[70, 71]

Nanotechnology in the treatment of periodontal disease

Tanaguchi introduced the term ―nanotechnology‖. Dr.Richard Phillips Feynman attributed

the discovery of nanotechnology. ―Nanotechnology is research and technology development

at the atomic, molecular or macromolecular level in the length scale of approximately 1-100

nm range, to provide a basic understanding of phenomena and materials at the nanoscale and

to form and use structures, devices, and systems that have novel properties and functions due

to their little and/or intermediate size‖. Various nanoparticles used in the field of

periodontology are carbon nanoparticles, Titanium nanotubes coated dental implants,

nanoceramics for bone regeneration, nanorobots for oral analgesia.[72]

New drugs for treating periodontal disease

Newer drugs like Resolvin are used in periodontal disease, as it lowers the recruitment of

neutrophils at the inflammation site and reduces the cytokines and reactive oxygen species

and thus reduces inflammation. Other drugs like Adalimumab, Golimumab, anti-cytokine

loke Anakinra, Tocilizumab and RANKL inhibitors like Denosumab are also preferable as

they induce periodontitis but they are still under study. Reed et al. studied on amixicile a new

antibiotic which is a novel inhibitor of pyruvate ferredoxin oxidoreductase. A minimal

inhibitory concentration ranging from 0.5-1.5 micrograms per ml has inhibited the growth

and other central processes to virulence in an in-vitro study.[72]


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Ozone therapy in periodontology

Ozone therapy has a long history of research with humans along with the clinical application.

Joachim Hansler and Hans Wolff developed the ozone generator for medical use. Ozone has

been used for the following purposes: 1. Elimination of pathogens. 2. Restoration of proper

oxygen metabolism. 3. Induction of a friendly ecologic environment. 4. Increased circulation.

5. Immune activation. 6. Simulation of the humoral anti-oxidant system. Routes of

administration are Gaseous ozone, Ozonated water, Ozonized oil.[73]

In 2006 Huth et al study

has shown that ozone in aqueous form acts as a potential antiseptic agent and shows less

cytotoxicity compared to gaseous ozone.[74]

Kshitish and Laxman in 2010 performed a

randomized, double-blind, split-mouth study. The results showed a higher reduction in plaque

index(29%) and bleeding index(26%) using ozone irrigation. Ozone therapy was

contraindicated in pregnancy, Autoimmune disorder, Gravis, Alcohol intoxication, CVD, MI,

Ozone allergy and Hemorrhage.[75]

CONCLUSION

Periodontal diseases comprise a wide range of inflammatory conditions that affect the

supporting structures of the teeth (the gingiva, bone, and periodontal ligament), which could

lead to tooth loss and contribute to systemic inflammation. Chronic periodontitis

predominantly affects adults, but aggressive periodontitis may occasionally occur in children.

Periodontal disease initiation and propagation are through a dysbiosis of the commensal oral

microbiota (dental plaque), which then interacts with the immune defenses of the host,

leading to inflammation and disease. This pathophysiological situation persists through bouts

of activity and quiescence until the affected tooth is extracted or the microbial biofilm is

therapeutically removed and the inflammation subsides. The severity of the periodontal

disease depends on environmental and host risk factors, both modifiable (for example,

smoking) and non-modifiable (for example, genetic susceptibility). Prevention is achieved

with daily self-performed oral hygiene and professional removal of the microbial biofilm on a

quarterly or bi-Annual basis. New treatment modalities that are actively explored include

antimicrobial therapy, host modulation therapy, laser therapy, and tissue engineering for

tissue repair and regeneration.

ACKNOWLEDGMENTS

The authors express their gratitude to the Principal of Vijaya Institute of Pharmaceutical

Sciences for Women for providing necessary support in due course of the work.


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Conflict of Interest

The author confirms that this article content has no conflict of interest.

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