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Research progress of son dynamic therapy in the prevention and treatment of periodontal disease

Periodontal disease is an inflammatory disease that occurs in periodontal supporting tissues, affecting 15% to 20% of the world’s population. It is a common oral bacterial infection. The main method for the prevention and treatment of periodontal disease is to remove the initiating factor dental plaque biofilm. In terms of prevention, it mainly includes the use of toothbrushes, dental floss, and interdental brushes. In terms of treatment, it mainly includes supragingival surgery and subgingival curettage. (SRP) and auxiliary use of mouthwash and antibiotics, but these methods have certain limitations.

While describing the above prevention methods and limitations, this article introduces some cutting-edge research on periodontal disease prevention and treatment, focusing on the concept of sonodynamic therapy (SDT), its mechanism of action, and its role in periodontal disease.

  1. Prevention and treatment of periodontal disease

1.1 Routine prevention and treatment of periodontal disease

It is mainly used by patients to remove plaque by mechanical means. However, due to poor efficiency and methods of removing plaque by themselves, patients often cause gingivitis and then induce periodontal disease. In the conventional treatment of periodontal disease, the basic treatment of SRP has limitations: some areas with anatomical limitations such as the posterior axial angle or root bifurcation are often unable to reach the bottom of the periodontal pocket for thorough debridement with hand instruments. For cases related to actinomycetes, SRP alone cannot achieve the best therapeutic effect.

In drug treatment, the use of chlorhexidine mouthwash can inhibit bacteria to a certain extent, but it is cytotoxic; the use of antibiotics such as amoxicillin, metronidazole, and adriamycin is effective in the adjuvant treatment of periodontal disease, but such drugs There are certain drawbacks, such as the difficulty in permeating biofilms and the long-term use of drug resistance, so the use of mouthwash and antibiotics is not the best way to assist in the treatment of periodontal disease. In this case, some new ideas for the prevention and treatment of periodontal disease have emerged, which provide the possibility to improve the treatment efficiency and effectiveness of periodontal disease.

1.2 Progress in periodontal disease prevention and adjuvant treatment

The frontiers of periodontal disease prevention and treatment research mainly include the application of microorganisms, propolis extracts, metal materials, and photodynamic therapy (PDT), etc., all of which have certain antibacterial capabilities and potential capabilities for the prevention and treatment of periodontal disease. The use of other microbial population changes can reduce the number of periodontal disease-causing bacteria and then reduce the risk of periodontitis. Chen et al. found that the use of antibacterial methods to reduce the number of herpes viruses and bacterial pathogens can simultaneously reduce the number of periodontal pathogens, which may be related to the synergistic effect between viruses and bacteria, but the use of drugs to reduce the number of herpes viruses will also produce drug resistance or even break The original ecosystem level.

Vohra et al. used probiotics as the experimental group during SRP and found that the effect was better than the simple use of SRP at a follow-up visit 3 months after treatment. The specific manifestation was that the periodontal bleeding index and probing bleeding level of the experimental group were lower. However, in the third and sixth months of follow-up visits, there was no significant difference in the level of periodontal exploration and attachment loss between the test group and the control group, which may indicate that the long-term effect of adjuvant probiotics is not ideal. The use of propolis extract has anti-inflammatory and antioxidant capabilities. Kizildag et al. found that propolis extract caffeic acid phenethyl ester can inhibit the oxidative stress response and alveolar bone loss in diabetic periodontitis rats, but the existing research is through the whole body Caffeic acid phenethyl ester is used to reduce the oxidative stress response in rat serum to inhibit bone loss. There is no study on the effect of local effect on periodontal.

In terms of metal materials, Fang et al. found that the titanium coating can prevent the adhesion of Porphyromonas gingivalis and has a higher local concentration, but the duration is too short to maintain. PDT is a new type of treatment developed with the development of fiber optic technology and laser medicine in the 1980s. It activates photosensitizers with specific wavelengths of visible light to kill cells at targeted sites.

Studies have confirmed that PDT can effectively reduce the number of periodontal disease’s main pathogenic bacteria Porphyromonas gingivalis and actinomycetes, and does not require systemic administration, so PDT can effectively prevent periodontal disease. However, PDT has a superficial site of action, and its ability to act on bacteria in deep periodontal pockets is poor. Based on the above progress in periodontal prevention and treatment, there is an urgent need for a new method of periodontal prevention and treatment that can solve the above shortcomings.

  1. SDT overview

2.1 The emergence of SDT

In 1989, when Japanese scholar Yumita et al. used hematoporphyrin derivatives as photosensitizers for PDT, they discovered that hematoporphyrin drugs can also cause significant cell damage through ultrasound activation, and proposed the concept of sonodynamic therapy. With the advancement of ultrasound medicine, some scholars have found that using ultrasound to activate some photosensitizers can also achieve killing effects, and define the sensitizer that mediates the effects of SDT as a sonosensitizer. Since then, relevant research on SDT has been launched.

2.2 SDT concept

SDT is a treatment method that uses ultrasound combined with sonosensitizer to kill target cells or pathogenic microorganisms. It mainly relies on ultrasound as an energy source to activate the sonosensitizer. In SDT, low-frequency ultrasound has the advantages of harmlessness, low price, and reusability, so it is widely used in medical diagnosis, treatment, and industry. For example, mediated microbial killing is used in medical scalers to remove plaque. In industry, it can reduce the bacterial load in food without affecting the food itself.

Ultrasound can trigger chemical changes in sonosensitizers under non-invasive conditions, and produce a killing effect on targeted tissues. There are many types of sonosensitizers used in SDT, mainly concentrated in porphyrins, xanthenes, quinolones, phenothiazines, non-steroidal anti-inflammatory drugs, etc. Among them, porphyrins and their derivatives have low toxicity. It is the most widely used type of sonosensitizer in SDT.

2.3 Comparison between SDT and PDT

2.3.1 Similarities between SDT and PDT

Both SDT and PDT can be used to treat periodontal disease. Both are non-invasive and non-invasive procedures with a certain degree of targeting and minimizing damage to surrounding normal tissues. In vitro, experimental studies have shown that after the use of SDT and PDT, the level of reactive oxygen species (ROS) in tumor cells has increased, and the increase in intracellular ROS content will lead to an increase in intracellular oxidative pressure, which in turn leads to cell death. The two can be used alone, in combination, or in combination with radiotherapy and chemotherapy.

2.3.2 Differences between SDT and PDT

In terms of function, compared with the short penetration of light waves, sound waves can reach deep tissues for action. The penetrating power of SDT has an appropriate tissue attenuation coefficient, which can safely and non-invasively focus the energy to target cells in the deep range while reaching deep lesions. Therefore, SDT has improved to some extent the limitation that PDT can only be used in the treatment of superficial diseases. It can not only kill cells but also minimize adverse reactions. In terms of the mechanism of action, the role of PDT mainly revolves around the generation of ROS, the destruction of blood vessels around the tumor, and the activation of the body’s immune response to target cells. The mechanism of action of SDT is quite different from that of PDT.

  1. SDT mechanism of action

Existing studies have shown that the mechanism of action of SDT includes acoustic cavitation, sonoluminescence, thermal effect, singlet oxygen mechanism, and delivery effect. Each mechanism is related to the other. The following is a description of these mechanisms. analyze.

3.1 Acoustic cavitation

Acoustic cavitation is the interaction between ultrasound and surrounding media, including two forms of stable cavitation and inertial cavitation. Stable cavitation uses ultrasonic vibration to form a liquid stream, which then mixes with the surrounding medium. Inertial cavitation is related to the generation of ROS: the bubbles generated by ultrasound acting on the surrounding medium will change with the periodic changes of ultrasound intensity, and their internal pressure will be irregularly stretched. When the volume of the bubble and the sound wave reaches resonance, they will quickly become internal Explosion, instantaneous high temperature and extreme pressure to the local auction site, and at the same time, the bubble will generate free radicals and other substances in the process of implosion to generate ROS, including peroxides, superoxides, and singlet oxygen, which form oxidative pressure on cells.

3.2 Sonoluminescence

When the ultrasound just reaches the strength of the bubble collapse, the sound wave acts on the surrounding medium to generate light. The light generated by the sound wave can activate the sensitizer to concentrate a large amount of ROS, destroy the bacterial cell membrane, protein, and DNA structure, and increase the sonosensitizer, bubbles, and surroundings. The reaction between the media achieves the killing of target cells.

3.3 Thermal effect

When the bubbles generated by ultrasound acting on the surrounding medium collapse, they will cause instantaneously high temperatures at the local hot spots, thereby realizing effective killing of the site of action. Firstly, high temperature can increase the kinetic energy of cell membranes, improve cell membrane permeability, and play an important role in the transfer of therapeutic agents to target organs; secondly, high temperature can cause coagulation and necrosis of pathogenic microorganism cells; finally, high temperature can decompose the sensitizer and pyrolyze the surrounding medium The water and other methods increase the content of ROS and increase the oxidative pressure in the target cells.

3.4 Singlet oxygen mechanism

Singlet oxygen is an excited oxygen molecule, which can cause cell peroxidation and thus play a killing effect. Yumita et al. found that when hematoporphyrin is used as a sonosensitizer for SDT treatment, histidine as an O-2 scavenger can reduce cell killing ability, confirming that singlet oxygen is generated in SDT.

3.5 Delivery

The microbubbles produced by the action of ultrasound have the ability to bring the therapeutic agent into the cell. Currently, microbubbles have been widely used for drug delivery. For example, doxorubicin (DOX) can be transported into the cell membrane by microbubbles under the action of ultrasound. This method can reduce the non-specific release of DOX and improve delivery efficiency.

  1. The effect of SDT on bacteria

A number of studies have shown that SDT has a significant killing effect on bacteria: Wang et al. found that SDT mediated by Hypocrellin B can effectively destroy the integrity of methicillin-resistant Staphylococcus aureus biofilm. Costley et al. found that the Rose Bengal-antibacterial peptide conjugate used for antibacterial SDT can effectively kill Staphylococcus aureus and Pseudomonas aeruginosa, and ultrasonic pretreatment of Pseudomonas aeruginosa biofilm can increase the diffusion of sonosensitizer by 2.6 times. , To further improve the killing effect of bacteria. There are also reports confirming that SDT has a significant killing effect on Candida albicans.

As an emerging treatment technology, SDT has been successfully applied to treat a variety of diseases, such as atherosclerosis, glioma, and cancer. Ultrasound alone can be used for a variety of antibacterial programs, which can eliminate microorganisms at the level of bacteria and viruses. Ultrasound combined with sonosensitizers increases the potential to activate ROS overcomes the resistance of biofilms, destroys the structure of biofilms, and kills bacteria in the membranes.

The mechanism of SDT killing bacteria includes the following aspects:

①SDT focused ultrasound can generate shear forces to form pores in the biofilm structure, increase the permeability of the cell membrane, and facilitate other drugs to penetrate the biofilm to produce killing effects.

② The sonosensitizer is delivered to the bacteria through the pores of the biofilm and is activated by ultrasound to induce the generation of ROS, which increases the internal oxidative pressure of the bacteria.

③Under the action of ultrasound, the cavitation around the bacterial cells produces light. Under the action of this light, the sonosensitizer changes from the ground state to the excited state to produce ROS, which mediates the photooxidation of the bacterial cells.

The ROS generated by the sonosensitizer in the activated state can further generate ROS through direct pyrolysis or pyrolysis with water. The basic experiments of the antibacterial effect of SDT and the study of the mechanism of killing bacteria show that SDT has a high application prospect for the treatment of periodontal disease.

  1. The application status and advantages of SDT in the prevention and treatment of periodontal disease

Experimental studies by Zhuang et al. found that SDT mediated by hematoporphyrin monomethyl ether (HMME) has a good therapeutic effect on periodontitis in rats, which is specifically manifested in the site between the first and second molars of the maxilla In the experiment, the rats in the experimental group had a significant reduction in the degree of alveolar bone loss compared with the control group and effectively reduced the inflammatory lesions of the periodontal tissue. It shows that SDT can inhibit bone resorption and has the ability to treat periodontal disease.

SDT also has incomparable advantages in the prevention and treatment of periodontal disease: On the one hand, the interaction between ultrasound and sonosensitizers can produce a large amount of ROS, which can form oxidative pressure on bacteria to achieve the killing effect. Because ROS has high cytotoxicity in bacteria, it can kill bacteria efficiently without adverse reactions such as drug resistance, so SDT can kill periodontal pathogens safely and harmlessly. On the other hand, SDT can penetrate tens of centimeters of soft tissue safely and non-invasively and has little effect on the surrounding normal tissues. It can effectively act on the periodontal pocket wall and deep bacteria. SDT has obvious advantages over other methods of treating periodontal disease, and it is expected to be applied clinically in the future.

  1. Conclusion

Although SDT is safe and effective, the research on SDT in the field of periodontal disease prevention and treatment at home and abroad is still in its infancy. At present, there are still some problems waiting for us to solve:

①The mechanism that affects SDT to kill bacteria is not completely clear, and there is no A large number of in vivo and in vitro experiments to study.

②The application of sonosensitizers needs further study. How to find a sonosensitizer with a lower price and faster bacteria removal efficiency is a question worthy of discussion.

③The ROS produced by SDT is beneficial in eliminating bacteria, but the specific method of ROS generation and the elimination method after generation are not yet known. Compared with traditional treatment methods, SDT has unparalleled advantages, ensuring that it has broad development prospects and use-value in the treatment of periodontal disease.

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