# Clinical Applications of Low-Intensity Pulsed Ultrasound and Its Underlying Mechanisms in Dentistry
## 7 Conclusions and Prospect  
As a non-invasive treatment, LIPUS has been found to contribute to bone regeneration, bone remodeling, and cell metabolism. It has been considered as a novel therapeutic tool in dentistry. The feasibility of LIPUS has been proven by both animal experiments and human control experiments. As previously described, LIPUS has great potential in periodontal tissue regeneration, OTM-related periodontal remodeling, implant bone integration, TMJ bone formation, and dentin-pulp complex repair. We discovered that the TGF-\(\beta\)1/Smad pathway has an effect on both TMJ-OA treatment and dentin-pulp complex repair, so this pathway may be a therapeutic target for TMJ-OA and dentin-pulp injury. Besides, the ratio of OPG/RANKL plays a regulatory role in OITRR and OTM, which suggests that boosting the amount of OPG may be a novel treatment idea. Nevertheless, the practical application in the human body is limited and its mechanism of is still in the exploratory stage. In addition, LIPUS mainly serves as a supporting measure in most oral diseases, which can speed up the treatment process of the disease, shorten the treatment time, and alleviate the pain. LIPUS is suggested for application with various parameters in treating different diseases. We found that the most common parameters of LIPUS are 1.5 MHz and 30 \(\text{maw}/\text{cm}^{2}\) for 20 \(\text{min}/\text{day}\) (Table 1). However, we found that the signaling pathways activated by LIPUS may also participate in the development of multiple diseases, such as organ fibrosis [128]. Therefore, whether the application of LIPUS in the human body will promote the occurrence and development of fibrosis or result in the emergence of adverse side effects is worth considering. In this case, the maximum single-use time and the maximum frequency of LIPUS should also be carefully studied. The lack of clarity on the use of LIPUS may also be one of the reasons why LIPUS has shown limited studies in humans. Actually, many effects of LIPUS remain unknown, so it is still necessary to strengthen the research on LIPUS in the future, especially regarding the underlying cellular and molecular mechanisms. It would be helpful to design models that can better simulate the human environment to explore the mechanisms of action of LIPUS in different oral diseases or the relationship between different mechanisms to make it more targeted to treat diseases. Besides, there is less research on implant osseointegration and dentin-pulp complex, so more research is required to expand the understanding of LIPUS. However, in studies on the bone biological role of LIPUS, animal experiments constitute the majority and animal models are mostly based on the tibia rather than the jaw. Further studies are needed to verify whether there are differences in LIPUS used in the tibia and jaw. More human trials or human tooth slice organ experiments are also urgent to validate the efficacy and safety of LIPUS. More importantly, the optimal frequency and duration of LIPUS in treating different oral diseases need to be found through controlled experiments in order to enhance the effectiveness and efficiency of the application of LIPUS. In conclusion, LIPUS was proven to have broad application prospects in the prevention and treatment of oral diseases, but its application remains a great challenge. Because LIPUS has a positive effect on a wide range of oral diseases, it will be possible to simultaneously