Applications of Photobiostimulation therapy in periodontal treatment

Introduction

Periodontal diseases, primarily characterized by inflammation and destruction of the supporting structures of the teeth, pose significant health challenges. Traditional treatment modalities include mechanical debridement, surgical interventions, and pharmacological therapies. However, these approaches often have limitations, including patient discomfort, risk of infection, and varying degrees of efficacy. In recent years, photobiostimulation (PBM), also known as low-level laser therapy (LLLT), has emerged as a promising adjunctive treatment in periodontal therapy. PBM involves the application of low-intensity light to stimulate cellular activity and promote tissue healing and regeneration.

Mechanism of Photobiostimulation

Photobiostimulation operates on the principle that light at specific wavelengths can trigger biological processes within cells. The primary mechanism involves the absorption of light by chromophores in the cells, leading to a series of photochemical reactions. Cytochrome c oxidase, a key enzyme in the mitochondrial respiratory chain, is one of the main chromophores targeted by PBM. When light of specific wavelengths (typically in the red to near-infrared spectrum, 600-1000 nm) is absorbed by these chromophores, it leads to a cascade of cellular events:

Enhancement of Mitochondrial Activity

The absorption of light by cytochrome c oxidase enhances its enzymatic activity, leading to an increase in mitochondrial respiration. This results in elevated production of adenosine triphosphate (ATP), the primary energy currency of the cell. Enhanced ATP production provides the energy necessary for various cellular processes, including proliferation, migration, and differentiation.

Modulation of Reactive Oxygen Species (ROS)

The light-induced activation of mitochondria also leads to the production of reactive oxygen species (ROS). At low to moderate levels, ROS act as signaling molecules that regulate various cellular functions, including gene expression and cell proliferation. PBM helps in maintaining ROS levels within a range that promotes cell signaling without causing oxidative stress or damage.

Release of Nitric Oxide (NO)

Photobiostimulation can also lead to the release of nitric oxide (NO) from intracellular stores. NO is a versatile signaling molecule involved in numerous physiological processes, including vasodilation, immune response modulation, and neurotransmission. In the context of PBM, NO plays a role in improving blood flow and oxygenation to the treated area, which supports tissue healing and regeneration.

Gene Expression and Protein Synthesis

PBM has been shown to influence gene expression and protein synthesis. The increased ATP and ROS levels, along with other signaling pathways activated by PBM, can lead to the upregulation of genes associated with cell proliferation, anti-inflammatory responses, and tissue repair. This results in the production of proteins and growth factors that are essential for cellular repair and regeneration.

Anti-Inflammatory Effects

One of the critical benefits of PBM is its anti-inflammatory effect. PBM modulates the levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α), reducing inflammation. It also promotes the release of anti-inflammatory cytokines, which help in resolving inflammation and promoting tissue healing.

Cellular Proliferation and Migration

Photobiostimulation enhances the proliferation and migration of various cell types, including fibroblasts, keratinocytes, and endothelial cells. These cells are crucial for tissue repair and regeneration. For instance, fibroblasts are responsible for synthesizing the extracellular matrix, which provides structural support to tissues, while endothelial cells are essential for angiogenesis (the formation of new blood vessels).

Angiogenesis

Angiogenesis is a critical process in tissue healing and regeneration, and PBM promotes this process by stimulating the proliferation and migration of endothelial cells. Enhanced angiogenesis improves blood supply to the treated area, providing necessary nutrients and oxygen for tissue repair.

Modulation of Pain

PBM has analgesic effects, which are beneficial for pain management. The mechanisms underlying these effects include the modulation of pain-related neurotransmitters, reduction of inflammation, and the influence of peripheral nerves’ conduction velocity. PBM can also reduce the production of pain mediators such as bradykinin and substance P, providing relief from discomfort and pain.

Applications of Photobiostimulation in Periodontal Therapy

Reduction of Inflammation:

Inflammation is a critical component of periodontal diseases, and its effective management is essential for successful periodontal therapy. Photobiostimulation (PBM), also known as low-level laser therapy (LLLT), has been shown to have significant anti-inflammatory effects, making it a valuable tool in reducing periodontal inflammation. The anti-inflammatory mechanisms of PBM are multifaceted and involve various cellular and molecular processes.

Modulation of Pro-inflammatory Cytokines

Cytokines are signaling molecules that play a central role in the inflammatory response. Pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) are typically elevated in inflamed periodontal tissues. PBM has been shown to modulate the production and release of these cytokines, leading to a reduction in inflammation. IL-1β is a potent pro-inflammatory cytokine that promotes the recruitment of inflammatory cells and the destruction of periodontal tissues. PBM reduces IL-1β levels, thereby diminishing its inflammatory effects and contributing to tissue preservation and healing. TNF-α is another key pro-inflammatory cytokine involved in periodontal inflammation. PBM downregulates TNF-α expression, reducing inflammation and tissue damage. IL-6 is involved in the acute phase of the inflammatory response. PBM has been shown to decrease IL-6 levels, contributing to the resolution of inflammation.

In addition to reducing pro-inflammatory cytokines, PBM promotes the production of anti-inflammatory cytokines, which help resolve inflammation and facilitate healing. IL-10 is a potent anti-inflammatory cytokine that inhibits the synthesis of pro-inflammatory cytokines. PBM increases IL-10 levels, which helps in dampening the inflammatory response and promoting tissue repair. TGF-β is involved in tissue regeneration and repair. PBM stimulates the production of TGF-β, which aids in the resolution of inflammation and the promotion of healing processes.

Oxidative stress is a condition characterized by an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses. It plays a significant role in periodontal inflammation. PBM helps in modulating ROS levels, maintaining them within a range that supports cellular signaling without causing oxidative damage. PBM-induced ROS at controlled levels can act as signaling molecules that regulate inflammation and cellular repair. By preventing excessive ROS production, PBM reduces oxidative stress and its associated inflammatory damage. PBM enhances the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase, which neutralize ROS and protect tissues from oxidative damage. This contributes to the reduction of inflammation.

PBM promotes cellular repair and regeneration, which is crucial for resolving inflammation and restoring periodontal health. PBM stimulates the proliferation of fibroblasts, the primary cells responsible for synthesizing the extracellular matrix. This leads to increased collagen production, which helps in repairing and regenerating inflamed periodontal tissues. PBM enhances the migration and proliferation of epithelial cells, which are essential for re-epithelialization and the formation of a protective barrier over inflamed tissues. Inflamed tissues often suffer from reduced blood flow and oxygenation, which can exacerbate inflammation and hinder healing. PBM improves vascularization and enhances blood flow to the treated area. PBM induces the release of nitric oxide (NO), a potent vasodilator that relaxes blood vessels and improves blood flow. Enhanced blood flow delivers oxygen and nutrients to the inflamed tissues, supporting their recovery. PBM promotes angiogenesis, the formation of new blood vessels, which improves tissue perfusion and oxygenation. This is critical for the healing of inflamed periodontal tissues.

Promotion of Wound Healing:

PBM enhances the healing of periodontal wounds by promoting the proliferation and migration of fibroblasts, which are essential for the synthesis of the extracellular matrix. Additionally, PBM stimulates angiogenesis, the formation of new blood vessels, which is critical for supplying nutrients and oxygen to the healing tissues. One of the key aspects of wound healing is the proliferation and migration of cells involved in tissue repair. PBM has been demonstrated to stimulate the activity of several cell types essential for wound healing. Fibroblasts play a critical role in wound healing by synthesizing extracellular matrix components, including collagen. PBM enhances fibroblast proliferation and collagen synthesis, leading to the formation of new connective tissue. Studies have shown that PBM can increase the expression of collagen type I and type III, which are crucial for the structural integrity of periodontal tissues. Keratinocytes are essential for re-epithelialization, the process by which new epithelial tissue covers a wound. PBM stimulates keratinocyte migration and proliferation, promoting faster re-epithelialization and wound closure. This is particularly important in periodontal therapy, where the rapid restoration of the epithelial barrier can prevent infection and further tissue damage. Endothelial cells are involved in angiogenesis, the formation of new blood vessels. PBM enhances the proliferation and migration of endothelial cells, leading to improved vascularization of the wound area. Enhanced blood supply provides the necessary nutrients and oxygen for tissue repair and regeneration.

Growth factors and cytokines are signaling molecules that regulate various aspects of wound healing. PBM influences the expression and activity of these molecules, creating an environment conducive to healing. PBM increases the levels of growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and transforming growth factor-beta (TGF-β). VEGF promotes angiogenesis, FGF stimulates fibroblast activity and collagen production, and TGF-β regulates cell proliferation and differentiation. The combined effect of these growth factors accelerates wound healing. PBM modulates the production of cytokines involved in inflammation and healing. By reducing pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α), and increasing anti-inflammatory cytokines such as interleukin-10 (IL-10), PBM creates a favorable environment for wound healing. Angiogenesis is crucial for providing oxygen and nutrients to the healing tissue. PBM stimulates angiogenesis through several mechanisms. PBM induces the release of nitric oxide (NO), a potent vasodilator that promotes blood vessel formation. NO enhances endothelial cell proliferation and migration, contributing to the development of new capillaries in the wound area.

As mentioned earlier, PBM increases the expression of VEGF, which is a key regulator of angiogenesis. VEGF stimulates the growth of new blood vessels, improving tissue perfusion and oxygenation, which are essential for wound healing. Oxidative stress, characterized by excessive levels of reactive oxygen species (ROS), can impair wound healing. PBM helps modulate ROS levels, maintaining them within a range that supports healing without causing cellular damage. PBM enhances the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase, which neutralize ROS and protect cells from oxidative damage. By reducing oxidative stress, PBM promotes a favorable environment for tissue repair.

Matrix remodeling is a critical phase of wound healing that involves the degradation of damaged extracellular matrix components and the synthesis of new ones. PBM facilitates this process by regulating the activity of matrix metalloproteinases (MMPs) and their inhibitors. MMPs are enzymes that degrade damaged extracellular matrix components. PBM modulates the activity of MMPs, ensuring that matrix degradation and synthesis are balanced for optimal tissue repair. PBM also influences the expression of TIMPs, which regulate MMP activity. By maintaining a balance between MMPs and TIMPs, PBM supports effective matrix remodeling and wound healing.

One of the significant challenges in periodontal therapy is the regeneration of alveolar bone lost due to disease. PBM has shown potential in promoting bone regeneration by stimulating osteoblast activity, increasing the expression of bone morphogenetic proteins (BMPs), and enhancing mineralization. This makes PBM a valuable adjunct in procedures such as guided tissue regeneration (GTR) and bone grafting. PBM has been reported to have antimicrobial properties, which can be beneficial in reducing the microbial load in periodontal pockets. The light energy can disrupt bacterial cell walls and inhibit the growth of periodontal pathogens. When combined with conventional scaling and root planing (SRP), PBM can enhance the effectiveness of periodontal debridement.

Pain Management:

Pain and discomfort are common complaints among periodontal patients, especially following surgical procedures. PBM has analgesic effects that can help in reducing postoperative pain and discomfort. The analgesic effects of PBM are multifaceted and involve several biological processes that collectively contribute to pain relief. PBM influences the levels of neurotransmitters involved in pain perception. For example, PBM has been shown to reduce the levels of substance P, a neuropeptide associated with pain transmission. By decreasing substance P levels, PBM reduces the intensity of pain signals transmitted to the brain. Inflammation is a common source of pain in periodontal disease. PBM reduces the levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). By decreasing inflammation, PBM alleviates pain associated with inflamed periodontal tissues. PBM has been shown to stimulate the production of endogenous opioids, such as endorphins and enkephalins. These naturally occurring pain-relieving molecules bind to opioid receptors in the nervous system, reducing pain perception and providing analgesia. PBM can alter the conduction velocity of nerves, which affects the transmission of pain signals. By modulating nerve activity, PBM can reduce the speed and intensity of pain signals, leading to pain relief. PBM enhances blood flow and microcirculation in the treated area. Improved blood flow helps to remove pain-inducing metabolites and delivers oxygen and nutrients to the tissues, which can alleviate pain and promote healing.

Clinical Evidence and Studies

Numerous clinical studies have investigated the efficacy of PBM in periodontal therapy. A systematic review and meta-analysis by Sousa et al. (2016) evaluated the effects of PBM on periodontal treatment outcomes. The analysis included randomized controlled trials and concluded that PBM, as an adjunct to SRP, significantly improved clinical attachment levels and reduced probing depths compared to SRP alone. Another study by Ozcelik et al. (2008) assessed the impact of PBM on the healing of periodontal pockets following SRP. The results indicated that PBM-treated sites exhibited faster and more pronounced improvements in clinical parameters, including reduced bleeding on probing and decreased pocket depths. Kamma et al. (2009) conducted a clinical trial to assess the anti-inflammatory effects of PBM in patients with aggressive periodontitis. The results demonstrated a significant decrease in pro-inflammatory cytokines (IL-1β, TNF-α) in the PBM-treated group, indicating the potential of PBM in managing periodontal inflammation. Pourabbas et al. (2014) conducted a split-mouth study to evaluate the effects of PBM on periodontal wound healing following flap surgery. The study reported that the PBM-treated sites exhibited faster wound healing, improved tissue regeneration, and reduced postoperative pain compared to the control sites. Lopes et al. (2015) examined the impact of PBM on wound healing after gingivectomy. The study found that PBM significantly enhanced epithelialization and collagen formation, leading to improved wound healing and reduced healing time. Kreisler et al. (2004) conducted a clinical trial to assess the effectiveness of PBM in reducing pain following periodontal surgery. The results showed that patients treated with PBM experienced significantly lower pain levels and a reduced need for analgesic medications compared to the placebo group.

Braun et al. (2012) evaluated the effects of PBM on clinical periodontal parameters in patients with chronic periodontitis. The study reported significant improvements in probing depth (PD) and clinical attachment level (CAL) in the PBM-treated group compared to the control group. Qadri et al. (2013) conducted a randomized controlled trial to assess the impact of PBM on periodontal clinical parameters and microbiological outcomes. The results indicated that PBM-treated patients exhibited significant reductions in PD, CAL, and periodontal pathogen levels, suggesting enhanced periodontal health. Sanz-Moliner et al. (2013) conducted a clinical trial to assess the efficacy of PBM as an adjunct to nonsurgical periodontal therapy. The results demonstrated that PBM significantly enhanced the clinical outcomes of nonsurgical periodontal treatment, leading to improved periodontal health. Zare et al. (2014) investigated the adjunctive use of PBM with scaling and root planing (SRP) in patients with chronic periodontitis. The study found that the combination of PBM and SRP resulted in greater reductions in PD and improvements in CAL compared to SRP alone, highlighting the synergistic effects of PBM (References are available in the book).

Protocols and Parameters

The effectiveness of PBM depends on various parameters, including the wavelength of the light, the energy density, the duration of exposure, and the treatment frequency. Commonly used wavelengths in periodontal therapy range from 600 to 1000 nm, which fall within the red and near-infrared spectrum. These wavelengths are well-absorbed by cellular chromophores and have optimal tissue penetration. Energy density, measured in joules per square centimeter (J/cm²), is a critical factor in determining the therapeutic dose. Studies suggest that an energy density range of 1 to 6 J/cm² is effective for periodontal applications. The duration of each treatment session can vary from a few seconds to several minutes, depending on the area being treated and the energy density used. Protocols for specific periodontal applications,

Reduction of Inflammation

• Wavelength: 660 nm (red) or 810 nm (near-infrared).
• Energy Density: 2-4 J/cm².
• Power Output: 50-100 mW.
• Exposure Time: 60-120 seconds per site.
• Frequency: 2-3 times per week for 2-3 weeks.
• Application: Directly to the inflamed gingival tissue.

Promotion of Wound Healing

• Wavelength: 660 nm (red) or 830 nm (near-infrared).
• Energy Density: 3-5 J/cm².
• Power Output: 50-200 mW.
• Exposure Time: 60-120 seconds per site.
• Frequency: 2-3 times per week for 3-4 weeks.
• Application: Directly to the surgical site or area of tissue injury.

Pain Management

• Wavelength: 810 nm (near-infrared) or 904 nm (near-infrared).
• Energy Density: 1-3 J/cm².
• Power Output: 30-100 mW.
• Exposure Time: 30-60 seconds per site.
• Frequency: Daily for the first week, then 2-3 times per week as needed.
• Application: Directly to the painful area, including soft tissues and TMJ (temporomandibular joint) regions.

Enhancement of Clinical Periodontal Parameters

• Wavelength: 660 nm (red) or 810 nm (near-infrared).
• Energy Density: 2-4 J/cm².
• Power Output: 50-100 mW.
• Exposure Time: 60-120 seconds per site.
• Frequency: 2-3 times per week for 4-6 weeks.
• Application: Along the gingival margin and periodontal pockets.

Safety and Side Effects

PBM is considered a safe and non-invasive therapy with minimal side effects. When used within the appropriate parameters, PBM does not induce thermal damage to the tissues. However, it is essential to adhere to the recommended guidelines to avoid potential risks such as eye exposure to laser light and overexposure leading to phototoxic effects.

Future directions and research

The field of PBM is continually evolving, and ongoing research aims to further elucidate its mechanisms and optimize its clinical applications. Future studies may focus on the synergistic effects of PBM with other therapeutic modalities, the development of standardized treatment protocols, and the long-term outcomes of PBM-treated periodontal patients. Combining PBM with stem cell therapy could significantly enhance tissue regeneration. PBM can stimulate stem cell proliferation and differentiation, promoting faster and more effective periodontal regeneration. Integrating PBM with advanced drug delivery systems, such as nanocarriers, can improve the localized delivery of anti-inflammatory and antimicrobial agents, potentially enhancing therapeutic outcomes. Development of smart PBM devices that can automatically adjust parameters based on real-time feedback from the tissue. These devices could use sensors to monitor tissue response and optimize wavelength, energy density, and exposure time for personalized treatment.

Further research into the molecular mechanisms of PBM can provide deeper insights into how it influences cellular processes. Understanding these pathways could lead to the development of targeted PBM protocols for specific periodontal conditions. Genomic and proteomic studies could identify specific genes and proteins modulated by PBM, offering biomarkers for treatment efficacy and aiding in the customization of therapy based on individual genetic profiles. Conducting large-scale, multicenter clinical trials to validate the efficacy and safety of PBM in diverse populations. These studies can help establish standardized protocols and guidelines for clinical practice. Establishing standardized PBM protocols and guidelines through collaboration with professional organizations and regulatory bodies. Standardization can ensure consistent and effective application of PBM across clinical settings.

Conclusion

Photobiostimulation represents a promising adjunctive therapy in periodontal treatment, offering benefits such as reduced inflammation, enhanced wound healing, bone regeneration, antimicrobial effects, and pain management. Clinical evidence supports its efficacy, and ongoing research continues to expand our understanding of its mechanisms and applications. As the field advances, PBM has the potential to become an integral component of comprehensive periodontal care, improving patient outcomes and quality of life.

References

References are available in the hardcopy of the website “Periobasics: A Textbook of Periodontics and Implantology”.