|Year : 2012 | Volume
| Issue : 2 | Page : 78-83
Scope of photodynamic therapy in periodontics and other fields of dentistry
V Shivakumar1, M Shanmugam1, G Sudhir2, S Pavithra Priyadarshoni3
1 Department of Periodontics, Chettinad Dental College & Research Institute, Kelambakkam, Chennai, India
2 Ganga Medical Centre & Hospital, Coimbatore, Tamilnadu, India
3 Dental Surgeon, Coimbatore, Tamilnadu, India
|Date of Web Publication||4-Sep-2012|
Department of Periodontics, Chettinad Dental College & Research Institute, Kelambakkam, Chennai
| Abstract|| |
The advancement in science and technology in the medical field amends a path for embedding new treatment modalities to the challenges presented by the viable diseases. The increasing use of lasers in dentistry and medicine reflects the great advances in this technology during recent decades. A. The gold standard for the non surgical treatment of periodontal disease remains mechanical periodontal debridement. The mechanical periodontal treatment has to be often sustained with various anti infectious means, such as antiseptics or antibiotics. Antimicrobial agents used systemically or as a local drug delivery further suppress the periodontal pathogens, increasing the benefits of conventional mechanical therapy. The emergence of resistant microorganisms and a shift in the microflora after extended use limit the use of antimicrobials. This created the foundation for our modern use of chemotherapy and emergence of photodynamic therapy. The oral cavity is especially suitable for photodynamic antimicrobial chemotherapy (PACT) because it is relatively accessible to illumination. A search was initiated to locate original research articles, review articles, and case reports pertaining to the key words: photodynamic therapy, periodontal treatment, photosensitizer, wound healing, laser, photodentistry. Electronic database was selected and articles were retrieved from PubMed and Google This article presents an overview of photodynamic therapy as it represents a novel therapeutic approach in the management of oral biofilms.
Clinical Relevance to Interdisciplinary Dentistry
- Photodynamic therapy is a non invasive treatment modality which can be used in all the major specialty treatments in the field of dentistry.
- Inflammation, soft tissue and bone healing, postoperative pain, and post treatment tooth hypersensitivity can be managed in pedodontia, oral surgery, peroidontics, endodontics, and conservative dentistry.
- Antimicrobial photodynamic therapy reduces bacterial contamination, especially during the surgical procedures.
Keywords: Periodontal treatment, photodynamic therapy, photosensitizer, wound healing
|How to cite this article:|
Shivakumar V, Shanmugam M, Sudhir G, Priyadarshoni S P. Scope of photodynamic therapy in periodontics and other fields of dentistry. J Interdiscip Dentistry 2012;2:78-83
|How to cite this URL:|
Shivakumar V, Shanmugam M, Sudhir G, Priyadarshoni S P. Scope of photodynamic therapy in periodontics and other fields of dentistry. J Interdiscip Dentistry [serial online] 2012 [cited 2014 Jul 25];2:78-83. Available from: http://www.jidonline.com/text.asp?2012/2/2/78/100598
| Introduction|| |
Recent years have seen an increased focus on using laser systems as an adjunct in periodontal therapy. In periodontics, the most commonly used are high-power lasers. CO2, Nd:YAG, and Er:YAG lasers have been used for calculus removal, osseous surgery, and soft-tissue management, such as gingivectomy, gingival curettage, and melanin pigmentation removal. 
Several studies have shown that processes such as inflammation, soft tissue and bone healing, and side effects such as postoperative pain and post-treatment tooth hypersensitivity can be positively influenced by laser photo therapy (LPT). ,, Besides this, the association of low-power lasers with photosensitizers, the so-called "antimicrobial photodynamic therapy" (aPDT), can also be used for reducing bacterial contamination of periodontal pockets. ,,
Because the antimicrobial activity of photosensitizers is mediated by singlet oxygen, photodynamic antimicrobial chemotherapy (PACT) has a direct effect on extracellular molecules, and the polysaccharides of an extracellular polymeric matrix also are susceptible to photodamage. Antioxidant enzymes, such as superoxide dismutase and catalase, protect against some oxygen radicals, but not against singlet oxygen.  This dual activity, not displayed by antibiotics, represents a significant advantage of PACT.
Photodynamic therapy (PDT) is the light-induced non-thermal inactivation of cells, microorganisms, or molecules. This utilizes light to activate a photosensitizing agent in the presence of oxygen. The exposure of the photosensitizer to light results in the formation of toxic oxygen species, causing localized photodamage and cell death. Clinically, this reaction is cytotoxic and vasculotoxic. Depending on the type of agent, photosensitizers may be injected intravenously, ingested orally, or applied topically.
There are two mechanisms for this last process. Type I reaction involves electron transfer directly from the photosensitizer producing ions, or electron/hydrogen removal from a substrate molecule to form free radicals. These radicals react rapidly with oxygen, resulting in the production of highly reactive oxygen species (superoxide, hydroxyl radicals, and hydrogen peroxide). Type II reactions produce the electronically excited and highly reactive state of oxygen known as singlet oxygen. Usually it involves a contribution from both the mechanisms. 
| Dyes (Photosensitizer)|| |
- (1) Tricyclic dyes (methylene blue, toludine blue O, and acridine orange) (2) Phthalocyanines (aluminum disulfonated phthalocyanine and cationic Zn(II) phthalocyanine)
- Chlorines: Chlorine e6, stannous (IV) chlorine e6, chlorine e6-2.5 N-methyl-d-glucamine (BLC1010), polylysine and polyethyleneimine conjugates of chlorine e6
- Porphyrines: Hematoporphyrin HCl, photofrin, and 5-aminolevulinic acid (5-ALA), benzoporphyrin derivative (BPD)
- Xanthenes: Erythrocine
- Monoterpene: Azulene
| Source of Light|| |
We have three light systems for the therapy:
- Diode laser systems: They are easy to handle, portable, and cost-effective.
- Non-coherent light sources: Preferred for treatment of larger areas and include tungsten filament, quartz halogen, xenon arc, metal halide, and phosphor-coated sodium lamps.
- Non-laser light sources include light-emitting diodes (LEDs). They are economical, light weight, and highly flexible. 
| Data Collection|| |
A search was initiated to locate original research articles, review articles, and case reports pertaining to the keywords: photodynamic therapy, periodontal treatment, photosensitizer, wound healing, laser, photodentistry. Electronic database was selected and articles were retrieved from PubMed and Google.
Studies on periodontal clinical parameters
In a study that included 30 patients, comparison was made based on the clinical parameter bleeding on probing (BOP) between sites that underwent scaling and root planing (SRP) alone and sites that were treated with adjuvant PDT. Significant diminishing of BOP was noted after photodynamic laser therapy, compared with SRP alone. The reduction of BOP was maintained both at 1 week and 1 month after PDT. One month after performing PDT, there was a discrete tendency to increase the bleeding scores, but at lower levels compared to the bleeding scores after SRP alone. 
Another study included 20 patients with untreated chronic periodontitis. Their results showed baseline median values for probing depth (PD), gingival recession (GR), and relative attachment level (RAL) which were not different in the test group and control group. Values for RAL, PD, sulcus fluid flow rate (SFFR), and BOP decreased significantly 3 months after treatment in the control group with a higher impact on the sites treated with adjunctive PDT, and the authors summarized that in patients with chronic periodontitis, clinical outcomes of conventional subgingival debridement can be improved by adjunctive PDT. 
Studies on the effect on periodontal microbes
Ten patients (between 40 and 50 years of age) with active periodontal sites (in a total of 253 teeth) were treated with SRP in a study. Based on the results of the study, patients treated with PDT achieved the greatest bacterial reduction among all examined individual germs and reported a reduction of 87.57% (P < 0.05). The total overall results for all groups improved at 7 days. After 1 month, patients treated with PDT produced remarkable reduction in bacterial count, i.e.. 80.11% (P > 0.05), and after 3 months, reduction in bacterial count was 91.37%. 
A study was conducted on a 7-day oral plaque biofilm formed on natural enamel surfaces in vivo using a previously reported in situ device. The study showed that the photosensitizer is taken up into the biomass of the biofilm and significant cell death is caused by PDT. In addition, the treated biofilms are much thinner than the control samples and demonstrate a different structure from the control samples, with little evidence of channels and a less dense biomass. It was clearly visible in transmission electron microscopy (TEM) of the in vivo-formed plaque biofilms which revealed considerable damage to bacteria in the biofilm, vacuolation of the cytoplasm, and membrane damage after the PDT. These results clearly demonstrate the potential value of PDT in the management of oral biofilms. 
Studies on the effect on periodontal structure
Researchers at São Paulo State University found that using PDT was an effective method to minimize destruction of periodontal tissue which can accompany treatment for periodontal diseases. In a rat population, PDT did minimal damage to periodontal tissues, in comparison to other techniques including SRP and antibiotic therapy. Also, PDT is significantly less invasive than other treatments for periodontal diseases. It can provide improved dentin hypersensitivity and reduced inflammation of the tissues surrounding the teeth, and allows tissues to repair faster. ,
A 2007 study by Andersen et al. used PDT in combination with conventional SRP and reported a significant reduction of pocket depth after 6-12 weeks, which increased the effectiveness of PDT in the treatment of chronic periodontitis. The amount of cementum that must be removed is also reduced significantly, which allows for better tissue regeneration without an increased risk of hypersensitivity. Furthermore, PDT's antibacterial effects are advantageous for patients with systemic diseases (such as cardiovascular diseases, diabetes, and immunosuppresion) and for those who display high resistance to antibiotic therapy. 
Studies on anti-inflammatory potential
Some studies have analyzed the inflammatory aspects of periodontal tissue and have shown that patients who have undergone conventional periodontal treatment in combination with LPT show better results. , It has been reported that LPT is able to reduce gingival inflammation and metalloproteinase 8 (MMP-8) expression when applied after SRP, as well as to reduce inflammatory cells on histology. 
Ozawa et al. showed that LPT significantly inhibits the increase in plasminogen activity induced in human periodontal ligament cells in response to mechanical tensile force.  Plasminogen activity is capable of activating latent collagenase, the enzyme responsible for cleaving collagen fibers. LPT also effectively inhibits prostaglandin E2 (PGE2) synthesis. The findings of a study suggest an inhibitory effect of LPT irradiation on interleukin (IL)-1β and interferon (IFN)-γ production and a stimulatory effect on platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-β. These alterations may be responsible for the anti-inflammatory effects of LPT and its positive effects on wound healing. 
Effect on wound healing
A study showed that sites receiving LPT (4 J/cm 2 , λ = 588 nm) had significantly faster surface epithelization than control sites, 3, 7, and 15 days after surgery. Additionally, complete wound healing was achieved faster in sites receiving LPT (within 18-21 days) than in control sites (within 19-24 days). In particular, the evidence from in vivo studies indicates that LPT may be beneficial in enhancing periodontal healing after gingivectomy, scaling, root planning, and intrabony defect surgery. 
Stein et al. reported that LPT has a biostimulatory effect on human osteoblast-like cells during the first 72 h after irradiation.  Histological studies using animal experimental models have also demonstrated that LPT can promote an increase in collagen fiber deposition, as well as in the amount of well-organized bone trabeculae after 30 days of induced-bone defect healing.  The effects of LPT on the bone healing process in surgically created bone cavities were evaluated using a biochemical assay. The results indicated that LPT acts by affecting calcium transport during new bone formation. 
Effect on pain and hypersensitivity management
LPT has been suggested as an alternative method for postoperative pain control. Compared to oral analgesics and nonsteroidal anti-inflammatory drugs, LPT can be advantageous because the therapeutic window for its anti-inflammatory action overlaps with its ability to improve tissue repair.  Some authors describe a possible stabilization of nerve cell membranes, probably due to the more stable conformation of the lipid bilayers induced by LPT, and the associated integral proteins of the nerve cell membrane. 
Several mechanisms are proposed to explain the decrease in pain after LPT in Dentinal Hypersensitivity (DH). The positive effects are mainly attributed to the formation of tertiary dentin and the reduction in sensory nerve activity.  Although information on the neurophysiological mechanism is not yet conclusive, it is postulated that LPT mediates an analgesic effect related to the depolarization of C-fiber afferents.
Photodynamictherapy in implantology
Laser PDT can be used in implantology to promote osseointegration and to prevent peri-implantitis. Studies have shown that laser photobiomodulation can be successfully used to improve bone quality around dental implants, allowing early wearing of prostheses.  The results of a study showed significant differences on the concentration of calcium hydrxyapatite on irradiated and control specimens and concluded that infrared laser photobiomodulation does improve bone healing.  The percentage of bone fill and re-osseointegration also improved with photobiomodulation. 
One of the most interesting developments over the last years has been the introduction of the 9.6-μm CO 2 laser. It has been shown in the recent literature that the use of this new device can preserve tissue, with almost no adverse effects at the light microscopic level. Intraoperatively used PDT or peri-implant care of ailing implants with the CO 2 laser seems to be more of value than the conventional methods. Data suggest that lethal photosensitization may have potential in the treatment of peri-implantitis. 
| Further Scope of PDT In Dentistry|| |
In a study, 24 rats were orally inoculated with Streptococcus mutans r three consecutive days and fed with a cariogenic diet and water with 10% of sucrose ad libitum during the experimental period. Twelve animals were treated by either light or photosensitizer and the remaining 12 animals were treated with 100 μM of methylene blue for 5 min and irradiated by an LED. Microbiological samples were collected before, immediately after, 3, 7, and 10 days after treatment, and the number of total microaerophiles was counted. The result showed that the number of total microaerophiles in the PDT group remained lower than in the control group until 10 days post-treatment. These findings suggest that PDT could be an alternative approach to reduce bacteria in dental caries. 
In another study, 30 anterior teeth from 21 patients with periapical lesions that had been treated with conventional endodontic treatment and antibiotic therapy were selected. Microbiological samples were taken after accessing the root canal, after endodontic therapy, and after PDT. It was concluded that the use of PDT added to conventional endodontic treatment leads to a further major reduction of microbial load and PDT is an efficient treatment to kill multidrug-resistant microorganisms. 
In a study, the authors aimed to investigate the potential use of laser for treating patients whose facial structures are predisposed to deviation in growth and development as much as chin-cups, face-masks, and headgear are used. Three groups of three hamsters were established: Group A, the normal development group or control group; Group B, three hamsters treated with a chin-cup; and Group C, the laser group. The long-term study over 7 months showed slower lower jaw growth in both groups B and C, relative to Group A. The importance of these findings is the implied possibility of laser use in the future to modify the growth and development of facial structures in humans. 
A study aimed to analyze the effect of single low-level laser therapy (LLLT) irradiation on pain perception in patients having fixed appliance treatment. Seventy-six patients (46 women, 30 men; mean age, 23.1 years) enrolled in this single-blind study were assigned to two groups. The results showed that LLLT immediately after multibanding reduced the prevalence of pain perception at 6 and 30 h. The authors concluded that LLLT might have positive effects in orthodontic patients not only immediately after multibanding, but also for preventing pain during treatment. 
Diagnosis and treatment of oral lesions
A relatively new approach in the diagnosis of oral lesions is topical application of 5-ALA. In 5-ALA-mediated photodynamic diagnosis, the difference in the fluorescence ratio between normal and premalignant/malignant tissue facilitates the distinction between malignant and nonmalignant lesions. Application of fluorescence in the diagnosis of oral leukoplakia in Eastman dental institute for oral healthcare sciences and and colleagues are examined 71 patients who exhibited clinically suspicious oral leukoplakia.  Three hours prior to examination, the patients rinsed their mouths with a 0.4% solution of 5-ALA for 15 min. This relatively short contact with 5-ALA was advantageous for diagnosis because the fluorescence intensity in malignant tissue decreases rapidly following 5-ALA application.
Oral leukoplakia and oral verrucous hyperplasia are common premalignant lesions that may transform into squamous cell or verrucous carcinoma. Topical 5-ALA-based PDT has been used to treat premalignant and malignant lesions in the oral cavity. PDT of the oral mucosa causes superficial necrosis, leaving little scarring and no cumulative toxicity. 5-ALA-based PDT appeared to be an effective treatment for oral leukoplakia. 
| Future Direction|| |
Although the therapeutic potential of light-based treatments has been recognized for some time, the expansion of PDT has occurred only recently, due to its promising results and clinical simplicity. While PDT is currently applied mostly in oncological therapy, in the future, it will most likely be applied to other areas. Clinical PDT is continuing to grow because of the relatively recent availability of portable and dependable light sources.
Pre-clinical work has shown that photosensitizers are more toxic against microbial species than against mammalian cells, and that the illumination-based toxicity occurs much earlier in prokaryotic than in eukaryotic cells. PACT appears to be the most efficient for the treatment of localized and superficial infections such as mucosal and endodontic infections, periodontal diseases, caries, and peri-implantitis, which are the potential targets.
The concept of photodynamic laser therapy itself is very attractive because it selects the target tissue by "marking" it with the photosensitizer, and the therapy (laser energy) is active (focused) only on "marked" cells or tissues.
Development of new photosensitizers, more efficient light delivery systems, and further animal studies are required to establish the optimum treatment parameters before investigators can proceed to clinical trials and eventual clinical use.
The future of PDT will depend on the interactions between clinical applications and technological innovations. Allison et al.  have described PDT as the therapy that "is truly the marriage of a drug and a light", and as a result, only interdisciplinary research approaches can overcome all the difficulties and challenges of PDT.
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