Approximately half of the adult population is suffering from periodontal disease, and conventional periodontal treatment strategies can only slow the progression of the disease. As a kind of tissue engineering, periodontal regeneration brings hope for the treatment of periodontal disease. Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound with a frequency of 1-3 MHz and a much lower intensity (< 1W/cm2) than traditional ultrasound energy and output. LIPUS has been adopted for a variety of therapeutic purposes due to its bioeffects such as thermal, mechanical, and cavitation effects, which induce intracellular biochemical effects and lead to tissue repair and regeneration ultimately. In this systematic review, we summarize the basic research of LIPUS in the treatment of periodontal disease in periodontal disease animal models and the influence of LIPUS on the biological behavior (including promoting osteogenic differentiation of stem cells and inhibiting inflammatory response) and potential mechanism of periodontal ligament stem cells (PDLSCs), hoping to provide new ideas for the treatment of periodontal disease. We believe that LIPUS can be used as an auxiliary strategy in the treatment of periodontal disease and play an exciting and positive role in periodontal regeneration.

The use of low-intensity pulsed ultrasound (LIPUS) for promoting fracture healing has been Food and Drug Administration (FDA)-approved since 1994 due to largely its non-thermal effects of sound flow sound radiation force and so on. Numerous clinical and animal studies have shown that LIPUS can accelerate the healing of fresh fractures, nonunions, and delayed unions in pulse mode regardless of LIPUS devices or circumstantial factors. Rare clinical studies show limitations of LIPUS for treating fractures with intramedullary nail fixation or low patient compliance. The biological effect is achieved by regulating various cellular behaviors involving mesenchymal stem/stromal cells (MSCs), osteoblasts, chondrocytes, and osteoclasts and with dose dependency on LIPUS intensity and time. Specifically, LIPUS promotes the osteogenic differentiation of MSCs through the ROCK-Cot/Tpl2-MEK-ERK signaling. Osteoblasts, in turn, respond to the mechanical signal of LIPUS through integrin, angiotensin type 1 (AT1), and PIEZO1 mechano-receptors, leading to the production of inflammatory factors such as COX-2, MCP-1, and MIP-1β fracture repair. LIPUS also induces CCN2 expression in chondrocytes thereby coordinating bone regeneration. Finally, LIPUS suppresses osteoclast differentiation and gene expression by interfering with the ERK/c-Fos/NFATc1 cascade. This mini-review revisits the known effects and mechanisms of LIPUS on bone fracture healing and strengthens the need for further investigation into the underlying mechanisms.

The blood-brain barrier (BBB) poses a significant challenge to drug delivery for brain tumors, with most chemotherapeutics having limited permeability into non-malignant brain tissue and only restricted access to primary and metastatic brain cancers. Consequently, due to the drug\'s inability to effectively penetrate the BBB, outcomes following brain chemotherapy continue to be suboptimal. Several methods to open the BBB and obtain higher drug concentrations in tumors have been proposed, with the selection of the optimal method depending on the size of the targeted tumor volume, the chosen therapeutic agent, and individual patient characteristics. Herein, we aim to comprehensively describe osmotic disruption with intra-arterial drug administration, intrathecal/intraventricular administration, laser interstitial thermal therapy, convection-enhanced delivery, and ultrasound methods, including high-intensity focused and low-intensity ultrasound as well as tumor-treating fields. We explain the scientific concept behind each method, preclinical/clinical research, advantages and disadvantages, indications, and potential avenues for improvement. Given that each method has its limitations, it is unlikely that the future of BBB disruption will rely on a single method but rather on a synergistic effect of a combined approach. Disruption of the BBB with osmotic infusion or high-intensity focused ultrasound, followed by the intra-arterial delivery of drugs, is a promising approach. Real-time monitoring of drug delivery will be necessary for optimal results.

Bone recovery typically depends on the age of organisms or the prevalence of metabolic disorders such as osteoporosis, which is a metabolic condition characterized by decreased bone strength and bone mineral density (BMD). Therefore, low-intensity pulsed ultrasound (LIPUS), a non-invasive method for osteogenic stimulation, presents promising results. However, heterogeneity in animal study designs is a typical characteristic. Hence, we conducted a systematic review to evaluate the effectiveness of LIPUS in the recovery of experimental bone defects using rat models. We examined the areal and volumetric BMD to identify LIPUS doses to be applied and evaluated the accuracy reported by previous studies.
The Virtual Health Library regional portal, PubMed, Embase, EBSCOhost, Scopus and CAPES were reviewed for animal studies that compared fracture treatments based on LIPUS with sham or no treatments using rat models and reported BMD as an outcome. The tool provided by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) and the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist were used to assess the bias and quality of such studies.
Of the six studies reviewed, the most frequently used LIPUS dose had an ultrasonic frequency of 1.0 MHz, repetition rate of 0.1 kHz and pulse duration of 2000 μs. An intensity (ISATA) of 30 mW/cm2 was the most preferred for bone recovery. However, the BMD could not solely irrefutably evaluate the effectiveness of LIPUS in bone recovery as the results were discordant with each other. The discrepancies in experimental methodologies, low-quality classifications and high risk of bias in the selected studies, however, did not validate the undertaking of a meta-analysis.
On the basis of the BMD results, no sufficient evidence was found to recommend the use of LIPUS for bone recovery in rat models. Thus, this systematic review indicates that the accuracy of such reports must be improved to improve their scientific quality to facilitate a transition of LIPUS applications from pre-clinical research to clinic use.

BACKGROUND: Atypical fractures are caused by the combined effects of severe suppression of bone metabolism (SSBT) due to long-term bisphosphonate therapy and chronic repetitive bone microdamage. Atypical ulnar fractures (AUFs) due to SSBT are rare, and there is no standard treatment strategy for such fractures. The relevant literature was reviewed, and the treatment strategy for AUF is discussed.
METHODS: A systematic review was conducted. All studies on ulnar fractures in individuals with a history of bisphosphonate use were included, and the data were extracted and analyzed from the perspective of the therapeutic strategy.
RESULTS: Forty limbs of 35 patients were included. As for the treatment of AUF, 31 limbs were treated surgically, and conservative treatment with casting was performed for 9 limbs. The bone fusion rate was 22/40 (55.0%), and non-union was seen in all patients treated conservatively. There was a significant difference in the bone fusion rate between patients with surgical treatment and those with conservative treatment. The bone fusion rate of patients with parathyroid hormone (PTH) and surgery was 82.3% (14/17 limbs); the bone fusion rate with PTH and bone graft was 69.2% (9/13 limbs). However, there were no significant differences in the fusion rate in the groups with or without PTH, with or without bone grafting, or the combination of the two treatments. There was also no significant difference in the bone fusion rate in the groups with or without low-intensity pulsed ultrasound (LIPUS) treatment.
CONCLUSIONS: Based on the literature review, surgery is necessary to achieve bone union, but surgery alone is not adequate to achieve bony union. Bone grafting and the administration of PTH and LIPUS may promote early bone fusion, but the present study did not show significant advantages of these additional treatments for bone union.

Periodontitis is a chronic inflammatory condition triggered by oral bacteria. A sustained inflammatory state in periodontitis could eventually destroy the alveolar bone. The key objective of periodontal therapy is to terminate the inflammatory process and reconstruct the periodontal tissues. The traditional Guided tissue regeneration (GTR) procedure has unstable results due to multiple factors such as the inflammatory environment, the immune response caused by the implant, and the operator\'s technique. Low-intensity pulsed ultrasound (LIPUS), as acoustic energy, transmits the mechanical signals to the target tissue to provide non-invasive physical stimulation. LIPUS has positive effects in promoting bone regeneration, soft-tissue regeneration, inflammation inhibition, and neuromodulation. LIPUS can maintain and regenerate alveolar bone during an inflammatory state by suppressing the expression of inflammatory factors. LIPUS also affects the cellular behavior of periodontal ligament cells (PDLCs), thereby protecting the regenerative potential of bone tissue in an inflammatory state. However, the underlying mechanisms of the LIPUS therapy are still yet to be summarized. The goal of this review is to outline the potential cellular and molecular mechanisms of periodontitis-related LIPUS therapy, as well as to explain how LIPUS manages to transmit mechanical stimulation into the signaling pathway to achieve inflammatory control and periodontal bone regeneration.

OBJECTIVE: To systemically review the effects of low-intensity pulsed ultrasound (LIPUS) on pain relief and functional recovery in patients with knee osteoarthritis (KOA).
METHODS: PubMed, Web of Science, Cochrane Library, Physiotherapy Evidence Database (PEDro), and China National Knowledge Infrastructure (CNKI) were used from inception to 18 March 2022.
METHODS: Meta-analysis was performed to evaluate pain and function recovery between control and LIPUS groups. Standardized mean difference (SMD) or mean difference (MD) and 95% confidence interval (CI) were calculated, and data were combined using the fixed or random-effect model.
RESULTS: Thirteen studies involving 807 patients with KOA were included. Patients\' outcomes treated by LIPUS were improved significantly, including Visual analog scale (VAS) score (MD = -0.95, 95% CI: -1.43 to -0.48，P < 0.001), Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score (MD = -4.35, 95% CI: -8.30 to -0.40, P = 0.0309), Lysholm score (SMD = 1.59, 95% CI: 1.29 to 1.90, P < 0.001), Lequesne index (MD = -1.33, 95% CI: -1.69 to -0.96, P < 0.001), Range of motion (ROM) (MD = 2.43, 95% CI: 0.39 to 4.46, P = 0.0197) and 50 meter walking time (SMD = 1.48, 95% CI: 0.46 to 2.49, P = 0.0044). Subgroup analyses showed monotherapy of LIPUS produced a better effect on reducing VAS score (P = 0.0213), and the shorter therapeutic period (≤4 weeks) produced a more significant effect on raising the WOMAC score (P = 0.0083).
CONCLUSIONS: LIPUS was beneficial for pain relief and functional knee recovery and maybe as an alternative therapy in KOA rehabilitation.

Therapeutic ultrasound has been studied for over seven decades for different medical applications. The versatility of ultrasound applications are highly dependent on the frequency, intensity, duration, duty cycle, power, wavelength, and form. In this review article, we will focus on low-intensity continuous ultrasound (LICUS). LICUS has been well-studied for numerous clinical disorders, including tissue regeneration, pain management, neuromodulation, thrombosis, and cancer treatment. PubMed and Google Scholar databases were used to conduct a comprehensive review of all research studying the application of LICUS in pre-clinical and clinical studies. The review includes articles that specify intensity and duty cycle (continuous). Any studies that did not identify these parameters or used high-intensity and pulsed ultrasound were not included in the review. The literature review shows the vast implication of LICUS in many medical fields at the pre-clinical and clinical levels. Its applications depend on variables such as frequency, intensity, duration, and type of medical disorder. Overall, these studies show that LICUS has significant promise, but conflicting data remain regarding the parameters used, and further studies are required to fully realize the potential benefits of LICUS.

Low-intensity pulsed ultrasound (LIPUS) is a developing technology, which has been proven to improve fracture healing process with minimal thermal effects. This noninvasive treatment accelerates bone formation through various molecular, biological, and biomechanical interactions with tissues and cells. Although LIPUS treatment has shown beneficial effects on different bone fracture locations, only very few studies have examined its effects on deeper bones. This study provides an overview on therapeutic ultrasound for fractured bones, possible mechanisms of action, clinical evidences, current limitations, and its future prospects.

Despite extensive research, nonunion continues to affect a nontrivial proportion of patients undergoing spinal fusion. Recently, preclinical studies have suggested that low-intensity pulsed ultrasound (LIPUS) may increase rates of spinal fusion. In this study, we summarized the available in vivo literature evaluating the effect of LIPUS on spinal fusion and performed a meta-analysis of the available data to estimate the degree to which LIPUS may mediate higher fusion rates. Across 13 preclinical studies, LIPUS was associated with a 9-fold increase in the odds of successful spinal fusion. Future studies are necessary to establish the benefit of LIPUS on spinal fusion in clinical populations.