Search

Maxillofacial bone defects can severely impact quality of life by impairing physiological functions such as chewing, breathing, swallowing, and pronunciation. Polyether ether ketone (PEEK) is commonly used for the repair of maxillofacial defects due to its mechanical adaptability, while its osteogenic properties still need refinement. Herein, we have utilized the piezoelectric effect exhibited by barium titanate (BTO) under low-intensity pulsed ultrasound (LIPUS) to develop an ultrasound responsive PEEK (PDA@BTO-SPEEK, PBSP) through the mediating effect of polydopamine (PDA), for repairing maxillofacial bone defects. After modification by PDA@BTO, PBSP possesses better hydrophilicity, which is conducive to cell growth and adhesion. Simultaneously, by virtue of the piezoelectric characteristics of BTO, PBSP obtains a piezoelectric coefficient that matches the bone cortex. Notably, when PBSP is stimulated by LIPUS, it can generate stable electricity and effectively accelerate the osteogenic differentiation of osteoblasts through the regulation of the Piezo1-induced calcium (Ca2+) influx and Akt/GSK3β/β-catenin pathway. In addition, PBSP presents satisfactory therapeutic effects in rat skull defect models, and its osteogenic efficiency can be further improved under LIPUS stimulation with high tissue penetration. Collectively, PBSP + LIPUS exhibits great potential as a promising alternative strategy for the repair of maxillofacial bone defects. [ABSTRACT FROM AUTHOR]

Abstract Maxillofacial bone defects can severely impact quality of life by impairing physiological functions such as chewing, breathing, swallowing, and pronunciation. Polyether ether ketone (PEEK) is commonly used for the repair of maxillofacial defects due to its mechanical adaptability, while its osteogenic properties still need refinement. Herein, we have utilized the piezoelectric effect exhibited by barium titanate (BTO) under low-intensity pulsed ultrasound (LIPUS) to develop an ultrasound responsive PEEK (PDA@BTO-SPEEK, PBSP) through the mediating effect of polydopamine (PDA), for repairing maxillofacial bone defects. After modification by PDA@BTO, PBSP possesses better hydrophilicity, which is conducive to cell growth and adhesion. Simultaneously, by virtue of the piezoelectric characteristics of BTO, PBSP obtains a piezoelectric coefficient that matches the bone cortex. Notably, when PBSP is stimulated by LIPUS, it can generate stable electricity and effectively accelerate the osteogenic differentiation of osteoblasts through the regulation of the Piezo1-induced calcium (Ca2+) influx and Akt/GSK3β/β-catenin pathway. In addition, PBSP presents satisfactory therapeutic effects in rat skull defect models, and its osteogenic efficiency can be further improved under LIPUS stimulation with high tissue penetration. Collectively, PBSP + LIPUS exhibits great potential as a promising alternative strategy for the repair of maxillofacial bone defects.

Medical titanium and titanium alloys were susceptible to infection following implantation due to their limited antibacterial properties. One effective approach to mitigate this risk was the application of antibacterial coatings on the medical titanium materials surface. Additionally, there was a pressing need in clinical practice to develop a titanium surface coating that can modulate antibacterial properties in response to external conditions. In this study, a zinc oxide-loaded silver nanorod arrays coating was fabricated on the titanium surface using intensity pulsed ultrasound and light as stimuli, aiming to achieve the desired regulation of antibacterial properties. The coating morphology and the silver distribution within the coating were investigated. The surface roughness and wetting angle were tested. The effect of low intensity pulsed ultrasound and light on the cumulative release of silver ions was studied, and its mechanism was analyzed. The bacteriostasis rate of the polarized ZnO-loaded silver nanorods array coating reached 99.96%. The synergistic bactericidal mechanism of piezoelectric effect, catalysis, silver ion bactericidal effect and nanorod puncture effect on bacteria was expounded. Finally, the ZnO-loaded silver nanorod array coating exhibited non-cytotoxicity and supported full osteoblast adherence morphology. The polarized coating was observed to be coated with abundant granular hydroxyapatite after immersion in simulated body fluids for 7 days. The results provide a possibility for modulating the antibacterial properties of titanium surface coatings in vitro. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of low intensity pulsed ultrasound (LIPUS) on inhibiting the abnormal cell phenotype of fibroblast-like synoviocytes in rheumatoid arthritis (RA-FLS) and possible mechanism. Method: Synoviocytes were isolated by using enzyme digestion, and the morphology of cells was observed under microscope. At the same time, the expression of Vimentin protein was detected by immunofluorescence method to identify RAFLS. Cells cultured in vitro were divided into four groups: control group, LIPUS group, tumor necrosis factor (TNF-α) group and TNF-α+LIPUS group or three groups: control group, interleukin-6 (IL-6) group and IL-6+LIPUS group. The effects of LIPUS on RA-FLS cell viability and proliferation were detected by CCK8 and EDU assay respectively, and the effects of LIPUS on RA-FLS migration were observed by scratch test and Transwell migration assay. RT-qPCR was used to detect the gene expression of important cytokines, chemokines and matrix metalloproteinases (MMPs) in RA-FLS. ELISA was used to further detect the effect of LIPUS on the expression of IL-6, a key effector of RA-FLS, and the effects of LIPUS on mitogen-activated protein kinase (MAPK) signaling pathway in RA-FLS were detected by Western Blot. Result: Purified RA-FLS were obtained. Firstly, LIPUS could suppress the cell activity (P<0.001) and proliferation (P=0.007) induced by TNF-α in RA-FLS cultured in vitro. However, the migration and the transcription levels of MMPs related to migration (MMP2 and MMP9) were not significantly different between groups (P> 0.05) . LIPUS could inhibit the high expression of IL-6 and interleukin-8 (IL-8) at the mRNA level in the inflammatory environment induced by TNF-α (P<0.001), but there was no significant difference in the suppression of interleukin-1β (IL-1β), MMP1 and MMP13 (P>0.05) . In addition, compared with untreated group, LIPUS could inhibit the secretion of IL-6 in RA-FLS induced by TNF-α (P<0.001), and also inhibited the proliferation of RAFLS induced by IL6 (P=0.003) . Finally, LIPUS could inhibit the phosphorylation of p38 MAPK and cJun Nterminal kinase (JNK) in MAPK signaling pathway (P=0.033), but the effect on the phosphorylation of extracellular signal-regulated kinas 1/2 (ERK1/2) was not significantly (P>0.05). Conclusion: LIPUS could reduce the abnormal proliferation of RA-FLS in inflammatory state without affecting its migration, which might be related to the inhibition of p38/JNK-IL-6 signaling pathway. [ABSTRACT FROM AUTHOR]

To standardize the research and clinical application of low intensity pulsed ultrasound (LIPUS) in the rehabilitation treatment of erectile dysfunction ( ED), the Genitourinary Medical Association of China International Exchange and Promotive Association for Medical and Health Care (GUA-CPAM), the Reproductive and Sexual Medicine Specialized Committee of the Tianjin Society of Integrative Medicine, the Beijing Zhongkejingfu International Academy of Andrology, and the Editorial Board of the Chinese Journal of Andrology organized domestic experts in urology and andrology to compile the "Chinese Expert Consensus on LIPUS for Standardized Treatment of Erectile Dysfunction" by reviewing relevant literatures and evidence-based medical evidence obtained in clinical practice. This consensus covers the physical and biological effects of microenergy LIPUS mechanical force, the mechanism of the treatment of ED, clinical indications and contraindications, therapeutic methods, safety and efficacy assessment, as well as the prospect of LIPUS in the treatment of other organ diseases, etc., which will undoubtedly provide a diagnostic and therapeutic guideline for LIPUS in the treatment of ED, and promotes the application of the new technology of microenergetic medicine in the field of regenerative rehabilitation treatment and benefit the patients. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: As a chronic and progressive neurodegenerative disease, Parkinson's disease (PD) still lacks effective and safe targeted drug therapy. Low-intensity focused ultrasound (LIFU), a new method to stimulate the brain and open the blood-brain barrier (BBB), has been widely concerned by PD researchers due to its non-invasive characteristics. Methods: PubMed was searched for the past 10 years using the terms 'focused ultrasound', 'transcranial ultrasound', 'pulse ultrasound', and 'Parkinson's disease'. Relevant citations were selected from the authors' references. After excluding articles describing high-intensity focused ultrasound or non-Parkinson's disease applications, we found more than 100 full-text analyses for pooled analysis. Results: Current preclinical studies have shown that LIFU could improve PD motor symptoms by regulating microglia activation, increasing neurotrophic factors, reducing oxidative stress, and promoting nerve repair and regeneration, while LIFU combined with microbubbles (MBs) can promote drugs to cross the BBB, which may become a new direction of PD treatment. Therefore, finding an efficient drug carrier system is the top priority of applying LIFU with MBs to deliver drugs. Conclusions: This article aims to review neuro-modulatory effect of LIFU and the possible biophysical mechanism in the treatment of PD, summarize the latest progress in delivering vehicles with MBs, and discuss its advantages and limitations. Neuro-modulatory effects of LIFU at the cellular or molecular level. Opening the BBB through the combination of LIFU and MBs. Biophysical mechanism of LIFU. [ABSTRACT FROM AUTHOR]

Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a major cause of infertility in female worldwide. Excessive apoptosis and impaired autophagy in ovarian granulosa cells are the main pathological mechanisms of POF. The total flavonoids from semen cuscutae (TFSC) are often used in the treatment of gynecological endocrine disorders. In addition, low intensity pulsed ultrasound (LIPUS) is report as an effective method to improve ovarian function. This study aims to investigate the protective effect of POF by the combined use of TFSC and LIPUS. POF rats model and granulosa cell model were successfully induced by tripterygium glycosides and cyclophosphamide, respectively. After that, model rats and cells received TFSC plus LIPUS administration. Then ovarian histomorphology, senescence, estrus cycle, and serum sex hormone levels were detected in rats. Ovarian tissue and granulosa cells autophagy and apoptosis levels were also assessed. Disturbed sex hormone levels, atrophied and senescent ovaries, and abnormal estrous cycle were found in POF rats. Meanwhile, cell autophagy was inhibited and cell apoptosis was activated in POF ovarian tissue and granulosa cells. However, TFSC combined with LIPUS improved these changes, and this combination treatment exhibited synergistic effects. The abnormal expression of the cell apoptosis-, autophagy-, and PI3K/AKT/mTOR signaling pathway-related proteins were also improved by combination treatment. The study found that the combination of TFSC and LIPUS can alleviate POF by modulating cell autophagy and apoptosis. The findings may provide a viable scientific basis for POF treatment. [ABSTRACT FROM AUTHOR]

It is very important to develop a new therapeutic strategy to cope with the increasing morbidity and mortality of chronic kidney disease (CKD). As a kind of physical therapy, low intensity pulsed ultrasound (LIPUS) has remarkable anti-inflammatory and repair-promoting effects and is expected to become a new therapeutic method for CKD. This study aims to clarify the treatment effect of LIPUS on CKD-related renal inflammation and fibrosis, and to further explore the potential signal network of LIPUS treatment for ameliorating chronic renal injury. A rat model simulating the progress of CKD was established by twice tail-vein injection of Adriamycin (ADR). Under anesthesia, bilateral kidneys of CKD rats were continuously stimulated by LIPUS for four weeks. The parameters of LIPUS were 1.0 MHz, 60 mW/cm2, 50% duty cycle and 20 min/d. LIPUS treatment effectively inhibited ADR-induced renal inflammation and fibrosis, and improved CKD-related to oxidative stress and ferroptosis. In addition, the therapeutic effect of LIPUS is closely related to the regulation of TGF-β1/Smad and Nrf2/keap1/HO-1 signalling pathways. This study provides a new direction for further mechanism research and lays an important foundation for clinical trials. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical efficacy and safety of low-intensity pulse ultrasound in the treatment of medial painful knee osteoarthritis. Methods A total of 10 patients with medial painful knee osteoarthritis were collected and treated with low-intensity pulsed ultrasound. VAS visual analogue scores, WOMAC and Lysholm knee osteoarthritis rehabilitation scale scores were performed before treatment, immediately after treatment, 1 week, 2 weeks and 4 weeks after treatment. The efficacy and safety were compared before and after treatment. The ultrasound images before and after treatment were compared to verify its safety. Result VAS, WOMAC and Lysholm scores were statistically significant before and immediately after treatment, 1 week and 2 weeks after treatment （P < 0.05）, but there was no statistically significant difference between them and 4 weeks after treatment （P > 0.05）. VAS decreased significantly before treatment, immediately after treatment, 1 week after treatment and 2 weeks after treatment, and were （5.26 ± 1.12）, （2.76 ± 0.92）, （2.74 ± 1.26）, （3.42 ± 0.93）, respectively. The secondary outcome indicators of WOMAC and Lysholm were significantly changed before treatment, immediately after treatment, 1 week after treatment and 2 weeks after treatment. They were （24.03 ± 4.43） and （66.93 ± 14.14）, （12.75 ± 1.63） and （79.86 ± 10.82）, （12.76 ± 1.82） and （81.93 ± 7.67）, （15.17 ± 2.73） and （77.08 ± 9.73）, respectively. No significant abnormality was found in the ultrasound images before and after treatment. Conclusion low-intensity pulsed ultrasound safely and effectively regulates the peripheral knee nerve in the treatment of painful knee osteoarthritis, providing a new idea for the intervention and treatment of clinical knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Medical Equipment Journal is the property of Chinese Medical Equipment Journal Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a major cause of infertility in female worldwide. Excessive apoptosis and impaired autophagy in ovarian granulosa cells are the main pathological mechanisms of POF. The total flavonoids from semen cuscutae (TFSC) are often used in the treatment of gynecological endocrine disorders. In addition, low intensity pulsed ultrasound (LIPUS) is report as an effective method to improve ovarian function. This study aims to investigate the protective effect of POF by the combined use of TFSC and LIPUS.Methods POF rats model and granulosa cell model were successfully induced by tripterygium glycosides and cyclophosphamide, respectively. After that, model rats and cells received TFSC plus LIPUS administration. Then ovarian histomorphology, senescence, estrus cycle, and serum sex hormone levels were detected in rats. Ovarian tissue and granulosa cells autophagy and apoptosis levels were also assessed.Results Disturbed sex hormone levels, atrophied and senescent ovaries, and abnormal estrous cycle were found in POF rats. Meanwhile, cell autophagy was inhibited and cell apoptosis was activated in POF ovarian tissue and granulosa cells. However, TFSC combined with LIPUS improved these changes, and this combination treatment exhibited synergistic effects. The abnormal expression of the cell apoptosis-, autophagy-, and PI3K/AKT/mTOR signaling pathway-related proteins were also improved by combination treatment.Conclusion The study found that the combination of TFSC and LIPUS can alleviate POF by modulating cell autophagy and apoptosis. The findings may provide a viable scientific basis for POF treatment.

ABSTRACTObjective It is very important to develop a new therapeutic strategy to cope with the increasing morbidity and mortality of chronic kidney disease (CKD). As a kind of physical therapy, low intensity pulsed ultrasound (LIPUS) has remarkable anti-inflammatory and repair-promoting effects and is expected to become a new therapeutic method for CKD. This study aims to clarify the treatment effect of LIPUS on CKD-related renal inflammation and fibrosis, and to further explore the potential signal network of LIPUS treatment for ameliorating chronic renal injury.Methods A rat model simulating the progress of CKD was established by twice tail-vein injection of Adriamycin (ADR). Under anesthesia, bilateral kidneys of CKD rats were continuously stimulated by LIPUS for four weeks. The parameters of LIPUS were 1.0 MHz, 60 mW/cm2, 50% duty cycle and 20 min/d.Results LIPUS treatment effectively inhibited ADR-induced renal inflammation and fibrosis, and improved CKD-related to oxidative stress and ferroptosis. In addition, the therapeutic effect of LIPUS is closely related to the regulation of TGF-β1/Smad and Nrf2/keap1/HO-1 signalling pathways.Discussion This study provides a new direction for further mechanism research and lays an important foundation for clinical trials.

AbstractBackground: As a chronic and progressive neurodegenerative disease, Parkinson’s disease (PD) still lacks effective and safe targeted drug therapy. Low-intensity focused ultrasound (LIFU), a new method to stimulate the brain and open the blood-brain barrier (BBB), has been widely concerned by PD researchers due to its non-invasive characteristics.Methods: PubMed was searched for the past 10 years using the terms ‘focused ultrasound’, ‘transcranial ultrasound’, ‘pulse ultrasound’, and ‘Parkinson’s disease’. Relevant citations were selected from the authors’ references. After excluding articles describing high-intensity focused ultrasound or non-Parkinson’s disease applications, we found more than 100 full-text analyses for pooled analysis.Results: Current preclinical studies have shown that LIFU could improve PD motor symptoms by regulating microglia activation, increasing neurotrophic factors, reducing oxidative stress, and promoting nerve repair and regeneration, while LIFU combined with microbubbles (MBs) can promote drugs to cross the BBB, which may become a new direction of PD treatment. Therefore, finding an efficient drug carrier system is the top priority of applying LIFU with MBs to deliver drugs.Conclusions: This article aims to review neuro-modulatory effect of LIFU and the possible biophysical mechanism in the treatment of PD, summarize the latest progress in delivering vehicles with MBs, and discuss its advantages and limitations.

Background: Developing effective therapeutic strategies to delay the progression of chronic kidney disease (CKD) remains a significant challenge. Low-intensity pulsed ultrasound (LIPUS) has demonstrated potential for treating CKD, but the underlying molecular mechanisms are still elusive. This study aimed to evaluate the therapeutic efficacy of LIPUS and to elucidate the involved genes and signaling pathways. Methods: The CKD model was established in rats using Adriamycin (ADR). The bilateral kidneys of CKD rats were continuously stimulated with LIPUS for a period of four weeks. The therapeutic efficacy was defined by renal function and histopathological evaluation. RNA sequencing was employed to profile the transcriptome of rat kidneys in each group. Cluster analysis was utilized to identify differentially expressed genes (DEGs), followed by enrichment analysis of their associated pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Results: LIPUS treatment improved ADR-induced renal dysfunction in the CKD group. Renal fibrosis and pathological damages were also alleviated in the ADR + LIPUS group compared to the ADR group. Cluster analysis identified 844 DEGs. GO enrichment analysis revealed enrichment in inflammatory response terms, while KEGG enrichment analysis highlighted the nuclear factor kappa B (NF-κB) signaling and ferroptosis-related pathways. Conclusion: Continuous LIPUS treatment improved ADR-induced renal fibrosis and dysfunction. The therapeutic effect of LIPUS was primarily due to its ability to suppress the CKD-related inflammation, which was associated with the modulation of the NF-κB and ferroptosis signaling pathways. These findings provide a new insight into the potential molecular mechanisms of LIPUS in treating CKD. Further research is necessary to confirm these findings and to identify potential therapeutic targets within these pathways.

Clinical biophysical stimulating strategies, which have significant effects on improving the function of organs or treating diseases by causing the salutary response of body, have shown many advantages, such as non-invasiveness, few side effects, and controllable treatment process. As a critical technique for stimulation, the low intensity pulsed ultrasound (LIPUS) has been explored in regulating osteogenesis, which has presented great promise in bone repair by delivering a combined effect with biomaterials. This review summarizes the musculoskeletal biomaterials that can be synergized with LIPUS for enhanced biomedical application, including bone regeneration, spinal fusion, osteonecrosis/osteolysis, cartilage repair, and nerve regeneration. Different types of biomaterials are categorized for summary and evaluation. In each subtype, the verified biological mechanisms are listed in a table or graphs to prove how LIPUS was effective in improving musculoskeletal tissue regeneration. Meanwhile, the acoustic excitation parameters of LIPUS that were promising to be effective for further musculoskeletal tissue engineering are discussed, as well as their limitations and some perspectives for future research. Overall, coupled with biomimetic scaffolds and platforms, LIPUS may be a powerful therapeutic approach to accelerate musculoskeletal tissue repair and even in other regenerative medicine applications. [ABSTRACT FROM AUTHOR]

This review summarizes the available recent literature on different mechanisms and parameters of pulsed ultrasound (US) that have been used during orthodontic treatments to prevent and repair root resorption. A literature search was conducted between January (2002) and September (2022) in the following databases: PubMed, Google-Scholar, Embase, and The-Cochrane-Library. After exclusions, a total of 19 papers were included in the present review. The most used US parameters with positive outcomes were frequency of 1.5 MHz, pulse repetition frequency of 1000 Hz, output intensity of 30 mW/cm2, duration of application of 20 min and total number sessions were 14 with a repetition interval of 1 day. The suggested mechanisms induced by US were alteration of cementoblasts, osteoblasts, osteoclasts, alkaline-phosphatase (ALP), runt-related-gene−2 (Runx2), osteoprotegerin (OPG), type-I-collagen (Col-I), C-telopeptide-type-I-collagen (CTX-I), hepatocyte-growth-factor (HGF), bone morphogenetic protein−2 (BMP−2), cyclooxygenase−2 (Cox−2), calcium (Ca2+), receptor activator of nuclear factor-kappa-B ligand (RANKL), and receptor activator of nuclear factor-kappa-B (RANK). Understanding mechanisms and deciding which parameters of US that can be used during orthodontic treatment to prevent and repair root resorption is a great challenge. This work summarizes all the available data that can aid this process and suggest that US is an effective noninvasive method not only in prevention and repairing of orthodontic induced root resorption but also in accelerating teeth movement. [ABSTRACT FROM AUTHOR]

Human periodontal ligament stem cells (hPDLSCs) are vital in cellular regeneration and tissue repair due to their multilineage differentiation potential. Low intensity pulsed ultrasound (LIPUS) has been applied for treating bone and cartilage defects. This study explored the role of LIPUS in the immunomodulation and osteogenesis of hPDLSCs. hPDLSCs were cultured in vitro, and the effect of different intensities of LIPUS (30, 60, and 90 mW/cm2) on hPDLSC viability was measured. hPDLSCs irradiated by LIPUS and stimulated by lipopolysaccharide (LPS) and LIPUS (90 mW/cm2) were co-cultured with peripheral blood mononuclear cells (PBMCs). Levels of immunomodulatory factors in hPDLSCs and inflammatory factors in PBMCs were estimated, along with determination of osteogenesis-related gene expression in LIPUS-irradiated hPDLSCs. The mineralized nodules and alkaline phosphatase (ALP) activity of hPDLSCs and levels of IκBα, p-IκBα, and p65 subunits of NF-κB were determined. hPDLSC viability was increased as LIPUS intensity increased. Immunomodulatory factors were elevated in LIPUS-irradiated hPDLSCs, and inflammatory factors were reduced in PBMCs. Osteogenesis-related genes, mineralized nodules, and ALP activity were promoted in LIPUS-irradiated hPDLSCs. The cytoplasm of hPDLSCs showed increased IκBα and p65 and decreased p-IκBα at increased LIPUS intensity. After LPS and LIPUS treatment, the inhibitory effect of LIPUS irradiation on the NF-κB pathway was partially reversed, and the immunoregulation and osteogenic differentiation of hPDLSCs were decreased. LIPUS irradiation enhanced immunomodulation and osteogenic differentiation abilities of hPDLSCs by inhibiting the NF-κB pathway, and the effect is dose-dependent. This study may offer novel insights relevant to periodontal tissue engineering. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of microfilament depolymerization in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) promoted by low intensity pulsed ultrasound (LIPUS). Methods Mouse BMSCs were randomly divided into 4 groups: blank control group, LIPUS group, LIPUS+DMSO group and LIPUS+cytochalasin D (CytoD) group. Alkaline phosphatase (ALP) activity of each group was detected by ALP staining. The expression and cellular localization of runt-related transcription factor 2 (RUNX2) were observed by immunofluorescence staining. Western blotting was performed to determine the protein changes of osteogenic differentiation-related genes, type I collagen (collagen 1), osteopontin (OPN) and runt-related transcription factor 2 (RUNX2), as well as the contents of filamentous actin (F-actin) and globular actin (G-actin) in the cells. The changes of cell morphology and microfilament cytoskeleton structure were observed with confocal laser scanning microscopy. Results As compared with the blank control group, LIPUS irradiation significantly enhanced the activity of ALP and upregulated the protein expression of osteogenic related genes Collagen1 (P < 0.01), OPN (P < 0.05) and RUNX2 (P < 0.01), with about a 1.5-fold increase in RUNX2 level (P < 0.01). Immunofluorescence staining showed that RUNX2 expression was obviously increased in the nucleus after LIPUS irradiation, and the cells shrank slightly with punctate distribution of G-actin in the cytoplasm. Western blotting revealed that the ratio of F-actin/G-actin was remarkably lower in the LIPUS group than the control group (P < 0.05). In addition, in comparison with the LIPUS+DMSO group, the LIPUS+CytoD group had greatly promoted the depolymerization of intracellular microfilaments, reduced ratio of F-actin/G-actin (P < 0.05), enhanced activity of ALP (P < 0.05), upregulated expression of RUNX2 in the nucleus (P < 0.05), and improved expression levels of the osteogenic related genes (P < 0.05). Conclusion LIPUS promotes the osteogenic differentiation of BMSCs, which may be related to LIPUS facilitating the depolymerization of microfilaments.

It is estimated that approximately 5% to 10% of fractures will evolve into nonunions. Nonunions have a significant impact on patient quality of life and on socioeconomic costs. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive therapy widely used within the orthopedic community to accelerate the healing of fresh fractures, to minimize delayed healing, and to promote healing of nonunions. In this case series, 46 nonunions and 19 fresh fractures were treated with LIPUS for at least three months or until fracture healing. Bone healing was assessed both at a radiological and a functional level. Of the nonunions healed, 89% had a mean healing time of 89 ± 53 days. In the group of fresh fractures, the healing percentage was 95% with a mean healing time of 46 ± 28 days. LIPUS treatment is proven to be safe and well tolerated; there were no adverse events related to the use of the device, even in the presence of internal fixations and infections. LIPUS therapy should be considered a low-risk option both as an adjunct to surgery or as a standalone therapy in the management of nonunion and fresh fractures.

Clinical biophysical stimulating strategies, which have significant effects on improving the function of organs or treating diseases by causing the salutary response of body, have shown many advantages, such as non-invasiveness, few side effects, and controllable treatment process. As a critical technique for stimulation, the low intensity pulsed ultrasound (LIPUS) has been explored in regulating osteogenesis, which has presented great promise in bone repair by delivering a combined effect with biomaterials. This review summarizes the musculoskeletal biomaterials that can be synergized with LIPUS for enhanced biomedical application, including bone regeneration, spinal fusion, osteonecrosis/osteolysis, cartilage repair, and nerve regeneration. Different types of biomaterials are categorized for summary and evaluation. In each subtype, the verified biological mechanisms are listed in a table or graphs to prove how LIPUS was effective in improving musculoskeletal tissue regeneration. Meanwhile, the acoustic excitation parameters of LIPUS that were promising to be effective for further musculoskeletal tissue engineering are discussed, as well as their limitations and some perspectives for future research. Overall, coupled with biomimetic scaffolds and platforms, LIPUS may be a powerful therapeutic approach to accelerate musculoskeletal tissue repair and even in other regenerative medicine applications.

ABSTRACT Objective: Low Intensity Pulsed Ultra Sound (LIPUS) is found to have stimulatory effect on bone healing and regeneration. This review aimed to assess whether LIPUS enhances bone regeneration and healing in terms of efficiency in improving clinical, radiographic, histologic parameters or serum and tissue biomarkers. Methods: A comprehensive search based on PRISMA guidelines with pre-determined eligibility criteria was conducted to identify randomized controlled clinical trials evaluating effectiveness of Low intensity pulsed ultrasound in bone regeneration and healing. The title and abstract of the entries in all languages yielded from the PubMed, Google scholar and Cochrane library were screened. Results: 14 eligible Randomized controlled trials testing the effectiveness of LIPUS was evaluated. More heterogeneity was seen in the screened studies with respect to sample characteristics, type of bone and outcome measures. The studies that screened histological parameters state that LIPUS is significantly beneficial than control. In terms of time for radiographic union, most of the studies stated that LIPUS was more effective than control but numberof studies are very few. Whereas studies which evaluated parameters such as healing time and radiographic union were showing highly inconsistent results regarding effectiveness of LIPUS. Conclusion: This review cannot give a definitive conclusion that LIPUS is effective in bone healing with respect to clinical parameters but a positive influence on radiographical and histological parameters in bone healing and regeneration is promising to pursue future research.

The present study evaluated the influence of Low-Intensity Pulsed Ultrasound (LIPUS) on the regeneration processes of non-critical-size bone defects in irradiated and non-irradiated rabbit tibias. Bone defects were surgically created on both tibiae of six rabbits. The control group had no additional treatment. In one intervention group, one tibia was irradiated with 15 Gy in a single dose. A second group was treated with LIPUS, and a third with a combination of both treatments. The control samples showed 83.10% ± 17.79% of bone repair after 9 weeks, while the irradiated bone had regenerated significantly less during the same period (66.42% ± 29.36%). The LIPUS treatment on irradiated bones performed a 79.21% ± 21.07% bone fill and could not significantly improve the response compared to the non-treated irradiated specimens. However, LIPUS treatment on non-irradiated bone showed bone formations beyond the size defect (115.91% ± 33.69%), which was a highly significant increase when compared to the control group or any irradiated group. The application of ultrasound to healthy bone produced highly significant and enhanced bone formations with 36.70% more regenerated bone when compared to the same application on irradiated bone. LIPUS vibration stimuli may be considered as a promising complementary treatment approach in non-irradiated bone regeneration procedures to shorten the treatment and enhance bone healing. In irradiated bones, the effect of ultrasound application is less clear, and further studies are needed to refine the dynamics of the present results. [ABSTRACT FROM AUTHOR]

Purpose: Several studies have evaluated the interest of Low Intensity Pulsed Ultrasound (LIPUS) in the osseointegration of dental implants in murine or rabbit models. However, the thinness and narrowness bones make it difficult to study the effect of LIPUS. The purpose of this study is to assess the ability of LIPUS to stimulate bone formation in contact with a titanium dental implant in a porcine model. Methods: Eight adults mini-pigs were used. An implant is placed on each tibial crest in the metaphysis. The right side was treated with LIPUS at 1 MHz and 300 mW/cm2 of acoustic intensity during 15 minutes per day on 5 consecutive days and during 42 days. The left side was not treated. The Bone Volume/Total Volume ratio (BV/TV), the Intersection Surface (IS) of the volume of interest by the binarized bone and the Trabecular bone Thickness (TbTh) around the implant were analyzed. Results: At 42 days, BV/TV ratio is significantly higher on the treated side (42,1+/-8,76% versus 32,31+/-10,11%, p < 0,02); as well as TbTh with 0,13+/-0,01 mm versus 0,10+/-0,01 mm (p < 0,01). IS is also significantly higher on the treated side (40,7+/- 12,68 mm² versus 33,68+/-9,44 mm² at 200 μm from the implant surface; p < 0,01). Conclusion: The present study showed that LIPUS can significantly increase bone formation and accelerate the healing process at the bone-implant interface in a porcine model. Its low toxicity, low immunogenicity and non-invasion make it a complementary treatment of choice for improving the bone formation around titanium implants. [ABSTRACT FROM AUTHOR]

Published literature shows low intensity extracorporeal shock wave therapy (LIESWT) and low intensity pulsed ultrasound (LIPUS) therapy to improve erectile function and penile hemodynamic by inducing neovascularisation and promoting tissue regeneration. Key opinion leaders across the Asia Pacific region attended the recent biennial meeting of the Asia Pacific Society for Sexual Medicine in Australia, and presented the current evidence on LIESWT and LIPUS for erectile dysfunction (ED). The clinical findings were internally discussed, and the quality of evidence was graded based on the Oxford Centre for Evidence- Based Medicine recommendations. Existing literature supports the use of LIESWT and LIPUS in men with ED, with many clinical studies reported encouraging results with improved erectile function, good safety profile and short-term durability. However, controversial exists due to sampling heterogeneity, non-standardised treatment protocol and lack of large multiinstitutional studies. There is a need to better define which subgroup of ED population is best-suited, and specific treatment protocol to optimise shock wave energy delivery. More stringent and larger multi-institutional randomised placebo-controlled trials are warranted before clinical adoption of LIESWT and LIPUS as the new standard of care for men with ED.

Objective: Low Intensity Pulsed Ultra Sound (LIPUS) is found to have stimulatory effect on bone healing and regeneration. This review aimed to assess whether LIPUS enhances bone regeneration and healing in terms of efficiency in improving clinical, radiographic, histologic parameters or serum and tissue biomarkers. Methods: A comprehensive search based on PRISMA guidelines with pre-determined eligibility criteria was conducted to identify randomized controlled clinical trials evaluating effectiveness of Low intensity pulsed ultrasound in bone regeneration and healing. The title and abstract of the entries in all languages yielded from the PubMed, Google scholar and Cochrane library were screened. Results: 14 eligible Randomized controlled trials testing the effectiveness of LIPUS was evaluated. More heterogeneity was seen in the screened studies with respect to sample characteristics, type of bone and outcome measures. The studies that screened histological parameters state that LIPUS is significantly beneficial than control. In terms of time for radiographic union, most of the studies stated that LIPUS was more effective than control but numberof studies are very few. Whereas studies which evaluated parameters such as healing time and radiographic union were showing highly inconsistent results regarding effectiveness of LIPUS. Conclusion: This review cannot give a definitive conclusion that LIPUS is effective in bone healing with respect to clinical parameters but a positive influence on radiographical and histological parameters in bone healing and regeneration is promising to pursue future research. [ABSTRACT FROM AUTHOR]

Background: Recently, ultrasonic neuromodulation research has been an important and interesting issue. Ultrasonic neuromodulation is possible by the use of low-intensity transcranial focused ultrasound (tFUS) to stimulate or inhibit the neural structures. The primary capability of this method is the improvement in the treatment progress of certain neurological and psychiatric disorders noninvasively. tFUS is able to modulate ionic currents and neural depolarization, causing the alteration in electrical properties of neurons.Objective: The study aims to investigate the effect of tFUS waves on the electrical behavior of neurons using the simulation method.Material and Methods: In the first part of this simulation study, the propagation of tFUS waves throughout the head was simulated to calculate the value of acoustic pressure at the cortex. In the second part, cortical neurons were simulated by a simple model of spiking neurons proposed by Izhikevich for three common dynamics. Then, the capacitance model was proposed to determine the alteration in the electrical behavior of the neurons during tFUS stimulation. Results: At the resting state, the electric potential of the neuron’s membrane through the tFUS stimulation has an amplitude of about 30 mv with the similar oscillatory behavior of the acoustic waveform; while,the ultimate electrical behavior of the neuron’s membrane indicates a decrease in the electric potential when the neurons fire.Conclusion: The electrical behavior of the neuron and the range of its membrane voltage modulated during ultrasonic stimulation. The reduction in the amplitude of membrane potential was observed while neuron spikes.

To investigate the promoting effects and mechanisms of low intensity pulsed ultrasound (LIPUS) on the migration of bone marrow-derived mesenchymal stem cells (BMSCs). The BMSCs migration was researched from cell and animal experiments. In the cell experiment, the BMSCs was treated using LIPUS (30 mW/cm2, 20 min/day, 2 days), and the wound healing and transwell migration were observed. In the animal experiment, the BMSCs labelled with green fluorescent protein (GFP) were injected into rats with femoral defects via the tail vein (1 × 106/mL). The healing of bone was detected using x-ray and sampled for hematoxylin & eosin (H&E) staining and fluorescence microscopy. About the mechanisms, the cellular F-actin of cytoskeleton was stained with FITC-phalloidin. The changes of BMSCs genes after LIPUS treatment were screened using microarray assay and verified using quantitative real-time polymerase chain reaction (qRT-PCR). The biological processes of those genes were predicted by KEGG analysis. The protein expression levels of FAK, ERK1/2 and myosin II related migration were detected using western blotting. The results showed LIPUS promoted the BMSCs migration (p .05) in vitro and in vivo than control group (p

Aim of this study was to evaluate effects of Low-intensity pulsed ultrasound on repair of articular cartilage defects. Low-intensity pulsed ultrasound (Lipus) can induce the differentiation and activation of chondrocytes. This study was designed to evaluate the effect of Lipus on articular cartilage defects in a sheep. Eight sheep were divided in to two groups. The animals received bilateraly, articular cartilage defects 4 mm in diameter and 2 mm in deep on the patellar groove and experimental groups were treated with intensity 200 mW/cm2, 20 min/day with low-intensity pulsed ultrasound for 2 month. Then both knee joints underwent surgery for remove of formed tissue sample from defects.The samples were evaluated by Quantitative real-time polymerase chain reaction (qRT-PCR), Safranin-o staining, Immunofluorescence Staining and Morphological characterization. The best and worst sample per group according to Macroscopic and micriscopic scoring were icentified. The results showed that the operated groups with-Lipus-treatment and without-Lipus treatment had considered statistically significant. Gross photography revealed that the defects in experimental groups were filled with proliferative tissue, while in control groups, a thin layer of proliferative tissue was formed in defects. qRT-PCR results showed the expression of coll2, sox9, aggrecan and Osteocalcin in experimental groups. Intense safranin-O staining show the formation cartilage tissue in ultrasound treated group, while loose safranin-o-staining were observed at the control groups. Immunofluorescence staining showed the type 2 Collagen protein expression. We suggest that low-intensity pulsed ultrasound provide the mechanistic basis force for articular cartilage repair and effective treatment modality for improving of articular cartilage defects. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of intramedullary fixation combined with low intensity pulsed ultrasound on the healing of middle femoral fracture in rabbits. Methods: 40 adult rabbits with femoral fracture were divided into control group and observation group. All rabbits should be banned from water and food before the operation, and their right hind limbs were prepared, weighed and anesthetized. The control group was treated with intramedullary fixation, and the observation group was treated with intramedullary fixation combined with low intensity pulsed ultrasound. 1, 2, 3, and 4 weeks after treatment, the rabbit’s fracture site was examined by imaging to determine the blurring of the rabbit’s fracture line, and samples were collected for histological examination every week. Check fracture healing after 4 weeks of treatment. Results: The proportion of healing degree of grade I, II and II in the observation group was lower than that in the control group, and the difference was statistically significant（P<0.05). The proportion of grade IV and grade V in the observation group was 35.0 % and 55.0 % respectively, which were higher than 5.0 % and 5.0 % of the control group, and the difference was statistically significant（P<0.05), the fuzzy degree score of fracture line in the observation group at 1 week, 2 weeks, 3 weeks and 4 weeks was higher than that of the control group The difference was statistically significant（P<0.05). Conclusion: In the treatment of fracture in rabbits, the speed of fracture healing can be significantly improved by the implementation of ultrasound in the treatment of femoral fracture. [ABSTRACT FROM AUTHOR]

The present study evaluated the influence of Low-Intensity Pulsed Ultrasound (LIPUS) on the regeneration processes of non-critical-size bone defects in irradiated and non-irradiated rabbit tibias. Bone defects were surgically created on both tibiae of six rabbits. The control group had no additional treatment. In one intervention group, one tibia was irradiated with 15 Gy in a single dose. A second group was treated with LIPUS, and a third with a combination of both treatments. The control samples showed 83.10% ± 17.79% of bone repair after 9 weeks, while the irradiated bone had regenerated significantly less during the same period (66.42% ± 29.36%). The LIPUS treatment on irradiated bones performed a 79.21% ± 21.07% bone fill and could not significantly improve the response compared to the non-treated irradiated specimens. However, LIPUS treatment on non-irradiated bone showed bone formations beyond the size defect (115.91% ± 33.69%), which was a highly significant increase when compared to the control group or any irradiated group. The application of ultrasound to healthy bone produced highly significant and enhanced bone formations with 36.70% more regenerated bone when compared to the same application on irradiated bone. LIPUS vibration stimuli may be considered as a promising complementary treatment approach in non-irradiated bone regeneration procedures to shorten the treatment and enhance bone healing. In irradiated bones, the effect of ultrasound application is less clear, and further studies are needed to refine the dynamics of the present results.

Objective: To study the effect of intramedullary fixation combined with low intensity pulsed ultrasound on the healing of middle femoral fracture in rabbits. Methods: 40 adult rabbits with femoral fracture were divided into control group and observation group. All rabbits should be banned from water and food before the operation, and their right hind limbs were prepared, weighed and anesthetized. The control group was treated with intramedullary fixation, and the observation group was treated with intramedullary fixation combined with low intensity pulsed ultrasound. 1, 2, 3, and 4 weeks after treatment, the rabbit’s fracture site was examined by imaging to determine the blurring of the rabbit’s fracture line, and samples were collected for histological examination every week. Check fracture healing after 4 weeks of treatment. Results: The proportion of healing degree of grade I, II and II in the observation group was lower than that in the control group, and the difference was statistically significant（P<0.05). The proportion of grade IV and grade V in the observation group was 35.0 % and 55.0 % respectively, which were higher than 5.0 % and 5.0 % of the control group, and the difference was statistically significant（P<0.05）; the fuzzy degree score of fracture line in the observation group at 1 week, 2 weeks, 3 weeks and 4 weeks was higher than that of the control group The difference was statistically significant（P<0.05). Conclusion: In the treatment of fracture in rabbits, the speed of fracture healing can be significantly improved by the implementation of ultrasound in the treatment of femoral fracture. [ABSTRACT FROM AUTHOR]

The results of experimental studies, the purpose of which was to study the effect of low-intensity pulsed ultrasound on the wettability of the surface of titanium dental implants are described. We studied 64 titanium dental implants. The control group consisted of 32 dental implants without ultra-sonication. The experimental group consisted of 32 dental implants, which were exposed to low-intensity pulsed ultrasound. Studies using low-intensity pulsed ultrasound showed that the wettability of the surface of all the experimental samples (32 dental implant) was 100 %, and the wettability of control samples (32 dental implant) was not observed. Thus the previously unknown property of low intensity pulsed ultrasound enabling the wetting of entire surface of the dental implant was discovered.

Non-union is a significant complication of fracture fixation surgery, and can negatively impact a patient's quality of life. Low intensity pulsed ultrasound (LIPUS) has been used to treat delayed or non-unions previously in the literature. The aim of this study was to determine the success rate of LIPUS treatment in patients with chronic fracture non-unions, and to establish the effect of systemic or local factors on its success. This was a retrospective, observational study which included all patients undergoing LIPUS treatment in a single institution. Patients deemed suitable for LIPUS underwent treatment for a period of 6 months from initiation. They were followed up with sequential radiographs to assess union at intervals of 6 weeks, 3 months, 6 months and 1 year. LIPUS treatment was considered to be successful when patients achieved clinical and radiological union, without the need for revision surgery. A total of 46 patients were included in the study; 8 were lost to follow – up, leaving 38 patients for the final analysis. The mean age of patients was 47.03 ± 19.7 with a male to female ratio of 1.2:1. Union was achieved in 57.89%; the rest underwent revision surgery. There was no significant association between outcomes after LIPUS treatment and patients' age, gender, smoking status or type of non-union. Patients with a small inter-fragment bone gap were more likely to have a successful outcome after LIPUS (p = 0.041). Time to treatment did not have a statistically significant impact on outcomes after LIPUS. Interestingly, all 6 patients with diabetes in the study managed to achieve union after LIPUS. This study demonstrates that LIPUS is not successful in a large proportion of patients with established fracture non-unions. However, it does represent a low risk treatment modality as an alternative to revision surgery, especially for patients with diabetes who have a small inter – fragment bone gap. More research in the form of large randomised controlled trials needs to be carried out to further assess the role of LIPUS in the treatment of non-unions. [ABSTRACT FROM AUTHOR]

Published literature shows low intensity extracorporeal shock wave therapy (LIESWT) and low intensity pulsed ultrasound (LIPUS) therapy to improve erectile function and penile hemodynamic by inducing neovascularisation and promoting tissue regeneration. Key opinion leaders across the Asia Pacific region attended the recent biennial meeting of the Asia Pacific Society for Sexual Medicine in Australia, and presented the current evidence on LIESWT and LIPUS for erectile dysfunction (ED). The clinical findings were internally discussed, and the quality of evidence was graded based on the Oxford Centre for EvidenceBased Medicine recommendations. Existing literature supports the use of LIESWT and LIPUS in men with ED, with many clinical studies reported encouraging results with improved erectile function, good safety profile and short-term durability. However, controversial exists due to sampling heterogeneity, non-standardised treatment protocol and lack of large multiinstitutional studies. There is a need to better define which subgroup of ED population is best-suited, and specific treatment protocol to optimise shock wave energy delivery. More stringent and larger multi-institutional randomised placebo-controlled trials are warranted before clinical adoption of LIESWT and LIPUS as the new standard of care for men with ED. [ABSTRACT FROM AUTHOR]

Introduction: Opening of the blood–brain barrier (BBB) by pulsed low intensity ultrasound has been developed during the last decade and is now recognized as a safe technique to transiently and repeatedly open the BBB. This non- or minimally invasive technique allows for a targeted and uniform dispersal of a wide range of therapeutic substances throughout the brain, including immune cells and antibodies. Methods: In this review article, we summarize pre-clinical studies that have used BBB-opening by pulsed low intensity ultrasound to enhance the delivery of immune therapeutics and effector cell populations, as well as several recent clinical studies that have been initiated. Based on this analysis, we propose immune therapeutic strategies that are most likely to benefit from this strategy. The literature review and trial data research were performed using Medline/Pubmed databases and clinical trial registry www.clinicaltrials.gov. The reference lists of all included articles were searched for additional studies. Results: A wide range of immune therapeutic agents, including small molecular weight drugs, antibodies or NK cells, have been safely and efficiently delivered to the brain with pulsed low intensity ultrasound in preclinical models, and both tumor control and increased survival have been demonstrated in different types of brain tumor models in rodents. Ultrasound-induced BBB disruption may also stimulate innate and cellular immune responses. Conclusions: Ultrasound BBB opening has just recently entered clinical trials with encouraging results, and the association of this strategy with immune therapeutics creates a new field of brain tumor treatment. [ABSTRACT FROM AUTHOR]

The use of low intensity pulsed ultrasound (LIPUS) therapy for bone healing and fracture treatment is increasingly considered as a therapeutic alternative with moderate economic cost and none or minimal adverse effects (e.g., low reaction to the conductive gel). However, there is some controversy regarding its scientific evidence. The present review seeks to shed some light on this controversy and to cover an area of study not occupied by previous or current work on ultrasound therapy. It is necessary to know the real impact of the treatment with low intensity pulsed ultrasound in patients with osteotomy, as well as its applicability as a post-surgery protocol to improve the recovery and rehabilitation processes and, at the end of the day, to reduce the time of disability., (Copyright © 2023 Sociedad Española de Rehabilitación y Medicina Física. Publicado por Elsevier España, S.L.U. All rights reserved.)

Despite the self-healing capacity of bone, the regeneration of critical-size bone defects remains a major clinical challenge. In this study, nanohydroxyapatite (nHAP)/high-viscosity carboxymethyl cellulose (hvCMC, 6500 mPa·s) scaffolds and low-intensity pulsed ultrasound (HA-LIPUS) were employed to repair bone defects. First, hvCMC was prepared from ramie fiber, and the degree of substitution (DS), purity, and content of NaCl of hvCMC samples were 0.91, 99.93, and 0.017%, respectively. Besides, toxic metal contents were below the permissible limits for pharmaceutically used materials. Our results demonstrated that the hvCMC is suitable for pharmaceutical use. Second, nHAP and hvCMC were employed to prepare scaffolds by freeze-drying. The results indicated that the scaffolds were porous, and the porosity was 35.63 ± 3.52%. Subsequently, the rats were divided into four groups ( n = 8) randomly: normal control (NC), bone defect (BD), bone defect treated with nHAP/hvCMC scaffolds (HA), and bone defect treated with nHAP/hvCMC scaffolds and stimulated by LIPUS (HA-LIPUS). After drilling surgery, nHAP/hvCMC scaffolds were implanted in the defect region of HA and HA-LIPUS rats. Meanwhile, HA-LIPUS rats were treated by LIPUS (1.5 MHz, 80 mW cm -2 ) irradiation for 2 weeks. Compared with BD rats, the maximum load and bone mineral density of HA-LIPUS rats were increased by 20.85 and 51.97%, respectively. The gene and protein results indicated that nHAP/hvCMC scaffolds and LIPUS promoted the bone defect repair and regeneration of rats significantly by activating Wnt/β-catenin and inhibiting OPG/RANKL signaling pathways. Overall, compared with BD rats, nHAP/hvCMC scaffolds and LIPUS promoted bone defect repair significantly. Furthermore, the research results also indicated that there are synergistic effects for bone defect repair between the nHAP/hvCMC scaffolds and LIPUS.

Non-ablative ultrasound (US)-based techniques to improve targeted tropism of systemically infused cell therapies, particularly mesenchymal stromal cell (MSC), have gained attention in recent years. Mechanotransduction following targeted US sonications have been shown to modulate tissue microenvironments by upregulating cytokines, chemokines, and trophic factors in addition to vascular cell adhesion molecules (CAM) that are necessary to promote tropism of MSC. While numerous US treatment parameters have demonstrated increased MSC homing, it remains unclear how the different mechanical US forces [i.e., acoustic radiation forces (ARF) or cavitation forces] influence tissue microenvironments. This study sonicated murine muscle tissue with pulsed focused ultrasound (pFUS) at 0.5 or 1.15 MHz each over a range of US intensities. Following sonication, tissue was assayed for the prostaglandins (PG) PGH2 and PGE2 as indicators of microenvironmental changes that would support MSC tropism. PGH2 and PGE2 levels were correlated to physical pFUS parameters and acoustic emissions measured by hydrophone. While ARF (pFUS with absence of cavitation signatures) was sufficient to increase PGH2 and PGE2, non-linear curve fitting revealed a frequency-independent relationship between prostaglandin production and mechanical index (MI), which accounts for increased cavitation probabilities of lower frequencies. The prostaglandin data suggested molecular changes in muscle would be particularly sensitive to cavitation. Therefore, low-intensity pulsed ultrasound (LIPUS) at 1 MHz was administered with low ARF (MI = 0.2) in combination with intravenous (IV) infusions of microbubble (MB) contrast agents. This combination upregulated prostaglandins and CAM without ultrasound-mediated microbubble destruction and ultimately promoted tropism of IV-infused MSC. This study revealed that accentuating non-destructive MB cavitation by US using parameters similar to diagnostic US contrast imaging increased MSC homing. Such approaches are particularly attractive to overcome clinical translation barriers of many still-experimental US parameters used in previous stem cell tropism studies.

Objectives: Low-intensity pulsed ultrasound (LIPUS) and SonoVue have been used widely for diagnosis and therapeutic treatment. The effects of LIPUS and SonoVue on the microvascular system and underlying molecular mechanisms have not been established. Methods: Cultured human renal glomerular endothelial cells (HRGECs) were treated with 5-min ultrasonic irradiation, 20% SonoVue or the combination of both treatments. Cell proliferation, viablity, and apoptosis were measured by MTT assay, Trypan blue exclusion assay and flow cytometry, respectively. Activation of extracellular regulated protein kinases (ERK) were examined by Western blot. Results: We found that LIPUS and SonoVue alone do not induce cytotoxicity of HRGECs; however, the combination of the two treatments reduces cell proliferation and increases cell death. In addition, the combination of LIPUS and SonoVue suppressed the activation of ERK 1/2 in HRGRCs. With pretreatment of the inhibitor of ERK1/2 signaling, PD98059, LIPUS, and SonoVue does not induce additional cell death and inhibition of proliferation. Conclusions: LIPUS combined with SonoVue induces cytotoxicity of HRGECs via repression of the ERK1/2 signaling pathway.

Abstract Background Bone tissue is one of the main sites for breast metastasis; patients diagnosed with advanced breast cancer mostly develop bone metastasis characterized by severe osteolytic lesions, which heavily influence their life quality. Low Intensity Pulsed Ultrasound (LIPUS) is a form of mechanical energy able to modulate various molecular pathways both in cancer and in health cells. The purpose of the present study was to evaluate for the first time, the ability of LIPUS to modulate osteolytic capability of breast cancer cells. Methods Two different approaches were employed: a) Indirect method -conditioned medium obtained by MDA-MB-231 cell line treated or untreated with LIPUS was used to induce osteoclast differentiation of murine macrophage Raw264.7 cell line; and b) Direct method -MDA-MB-231 were co-cultured with Raw264.7 cells and treated or untreated with LIPUS. Results LIPUS treatment impaired MDA-MB-231 cell dependentosteoclast differentiation and produced a reduction of osteoclast markers such as Cathepsin K, Matrix Metalloproteinase 9 and Tartrate Resistant Acid Phosphatase, suggesting its role as an effective and safe adjuvant in bone metastasis management. Conclusion LIPUS treatment could be a good and safety therapeutic adjuvant in osteolyitic bone metastasis not only for the induction properties of bone regeneration, but also for the reduction of osteolysis.

Low-intensity pulsed ultrasound (LIPUS) has been proved to promote the proliferation of myoblast C2C12. However, whether LIPUS can effectively prevent muscle atrophy has not been clarified, and if so, what is the possible mechanism. The aim of this study is to evaluate the effects of LIPUS on muscle atrophy in hindlimb unloading rats, and explore the mechanisms. The rats were randomly divided into four groups: normal control group (NC), hindlimb unloading group (UL), hindlimb unloading plus 30 mW/cm2 LIPUS irradiation group (UL + 30 mW/cm2), hindlimb unloading plus 80 mW/cm2 LIPUS irradiation group (UL + 80 mW/cm2). The tails of rats in hindlimb unloading group were suspended for 28 days. The rats in the LIPUS treated group were simultaneously irradiated with LIPUS on gastrocnemius muscle in both lower legs at the sound intensity of 30 mW/cm2 or 80 mW/cm2 for 20 min/d for 28 days. C2C12 cells were exposed to LIPUS at 30 or 80 mW/cm2 for 5 days. The results showed that LIPUS significantly promoted the proliferation and differentiation of myoblast C2C12, and prevented the decrease of cross-sectional area of muscle fiber and gastrocnemius mass in hindlimb unloading rats. LIPUS also significantly down regulated the expression of MSTN and its receptors ActRIIB, and up-regulated the expression of Akt and mTOR in gastrocnemius muscle of hindlimb unloading rats. In addition, three metabolic pathways (phenylalanine, tyrosine and tryptophan biosynthesis; alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism) were selected as important metabolic pathways for hindlimb unloading effect. However, LIPUS promoted the stability of alanine, aspartate and glutamate metabolism pathway. These results suggest that the key mechanism of LIPUS in preventing muscle atrophy induced by hindlimb unloading may be related to promoting protein synthesis through MSTN/Akt/mTOR signaling pathway and stabilizing alanine, aspartate and glutamate metabolism.

Introduction: Proportion of aged people has increased due to improvement in longevity. With advancing age bones loose mass, get weakened, become more prone to osteoporotic fractures. Development of osteoporosis is silent with reduction in total bone mineral content. Bone mineral density is the most important parameter which can measure gravity of OP. The T-score of -2.5 or below indicates OP leading to fractures commonly in bones of spine, hip and distal extremities. Objective: Purpose of this review is to find out currently available as well as future approaches those could be beneficial in faster recoveries. Method: Major databases were searched from inception to till January 2020. Relevant main articles and cross references were evaluated. In addition, findings were compared to a previously published review. Pharmacological and bio-molecule interventions decrease bone depletion by reducing bone resorption and enhancing bone formation process, and other external stimuli like strengthening muscular and skeletal tissues are employed to prevent OP and accelerate fracture healing and normal functioning. Results: A literature review of such interventions showed that bisphosphonates and selective estrogen receptor modulator treatment reduces fracture risks in osteoporosis and increase callus formation during fracture repair but do not reduce total time of fracture healing. Parathyroid hormone (PTH) and its analogues prevent OP by promoting callus formation as well as osteogenesis, enhance coupled remodelling and amount of mineralized tissue. When PTH is combined with bone morphogenetic proteins (BMP) improve mechanical functioning by integrating new bone tissue with old bone tissue. Restraining and supportive therapies like the physical exercises could be beneficial to minimize gravity of osteoporosis. Electromagnetic field therapy and pulsed ultrasonic therapy could be useful after surgical management of fracture or delayed union. Conclusion: To identify the quantitative effect of these therapies in isolation or in combination, clinical trials under proper experimental settings are especially important. Unlike the therapies for fracture repair in nonosteoporotic patients, the line of treatment and duration of each therapy in isolation or in combination with pharmacological agents, biomolecules, physical stimuli, exercises and lifestyles are necessary. [ABSTRACT FROM AUTHOR]

Low Intensity Pulsed Ultrasound Therapy (LIPUS) is a non-invasive treatment and aims to reduce fracture healing time and avoid non-union by delivering micro-mechanical stress to the bone to stimulate bone healing. In 2018, the National Institute for Health and Clinical Excellence (NICE) recommended that the evidence for LIPUS to promote healing of delayed-union and non-union fractures raised no major safety concerns, but the current evidence on efficacy is inadequate in quality. Little is known about the potential benefits of LIPUS for fracture healing in diabetic patients. In this article, we review the current evidence of LIPUS therapy both in animal and human studies and its possible application on fractures in diabetics. [ABSTRACT FROM AUTHOR]

Ultrasound techniques can be used to characterize and stimulate dental implant osseointegration. However, the interaction between an ultrasonic wave and the implant-bone interface (IBI) remains unclear. This study-combining experimental and numerical approaches-investigates the propagation of an ultrasonic wave in a dental implant by assessing the amplitude of the displacements along the implant axis. An ultrasonic transducer was excited in a transient regime at 10 MHz. Laser interferometric techniques were employed to measure the amplitude of the displacements, which varied 3.2-8.9 nm along the implant axis. The results demonstrated the propagation of a guided wave mode along the implant axis. The velocity of the first arriving signal was equal to 2110 m.s-1, with frequency components lower than 1 MHz, in agreement with numerical results. Investigating guided wave propagation in dental implants should contribute to improved methods for the characterization and stimulation of the IBI. [ABSTRACT FROM AUTHOR]

The management of hand and wrist nonunions is challenging and alternatives or adjuncts to surgery to promote healing are an attractive prospect. Low-intensity pulsed ultrasound (LIPUS) is reported to improve bone healing and is supported for use in nonunions. However, evidence supporting its use for established nonunions is based largely on long bones, with little evidence guiding use in the hand and wrist. The objective of this study is to present our experience using LIPUS in established nonunions of the hand and wrist. This is a retrospective cohort study of hand and wrist nonunions managed with LIPUS in two UK tertiary referral centers. Nonunion was defined as the failure of fracture healing at a minimum of 9 months post injury. Demographic and clinical data including nonunion site, union rates, surgery and time from surgery to LIPUS application were obtained from electronic patient and LIPUS device records. Patients were subcategorized into early or delayed LIPUS applications groups. Twenty-six hand and wrist nonunions were treated with LIPUS alone or as a surgical adjunct. The overall union rate was 62%. Age, sex, fracture characteristics and previous treatment had no significant effect on union rates. There was no association between LIPUS timing and union following adjustment for co-variates. Our findings suggest previously quoted union rates using LIPUS for lower limb nonunions may not be achievable in the hand and wrist. However, LIPUS offers a safe adjunct to surgery and may offer a potential alternative when surgery is not feasible. Further prospective comparative studies are required before the efficacy of LIPUS for hand and wrist nonunions is proven. [ABSTRACT FROM AUTHOR]

To investigate the promoting effects and mechanisms of low intensity pulsed ultrasound (LIPUS) on the migration of bone marrow-derived mesenchymal stem cells (BMSCs). The BMSCs migration was researched from cell and animal experiments. In the cell experiment, the BMSCs was treated using LIPUS (30 mW/cm2, 20 min/day, 2 days), and the wound healing and transwell migration were observed. In the animal experiment, the BMSCs labelled with green fluorescent protein (GFP) were injected into rats with femoral defects via the tail vein (1 × 106/mL). The healing of bone was detected using x-ray and sampled for hematoxylin & eosin (H&E) staining and fluorescence microscopy. About the mechanisms, the cellular F-actin of cytoskeleton was stained with FITC-phalloidin. The changes of BMSCs genes after LIPUS treatment were screened using microarray assay and verified using quantitative real-time polymerase chain reaction (qRT-PCR). The biological processes of those genes were predicted by KEGG analysis. The protein expression levels of FAK, ERK1/2 and myosin II related migration were detected using western blotting. The results showed LIPUS promoted the BMSCs migration (p <.05) without significant temperature changes (p >.05) in vitro and in vivo than control group (p <.05). The cytoskeletal rearrangement was carried out, and the ITGA8 gene related with cell migration was found with high expression after LIPUS treatment (p <.05). FAK inhibitor (PF-573228) and ERK1/2 inhibitor (U0126) were proved, in turn, decreased the BMSCs migration induced using LIPUS (p <.05). LIPUS can promote the BMSCs migration in vitro and in vivo, one mechanism may be related to the activation of FAK-ERK1/2 signalling pathways using LIPUS.Experiments in vivo and in vitro were designed to explore the migration and mechanisms of BMSCs treated using LIPUS. [ABSTRACT FROM AUTHOR]

To establish an axon regeneration regulatory network for optimal selection, and explore the role of low intensity pulsed ultrasound in the network. The axon regeneration regulatory network involving axon regeneration-related proteins NGF, BDNF and PirB was constructed by using GO and KEGG. The maximum possible pathway acting on axon regeneration was screened by Bayesian network theory. The node of low - intensity pulsed ultrasound in NGF - involved axon regeneration network was complemented by combining literature methods. The NGF, BDNF and PirB-involved axonal regeneration regulatory pathway was successfully constructed. The low intensity pulsed ultrasound played a role in axon regeneration by acting on ERK1/2-CREB pathway and GSK-3β. NGF-TrKA-Rap1-ERK1/2-CREB-Bcl-2 was optimized as optimal pathway by Bayesian theory. The regulatory pathway of axon regeneration involving nerve growth related factors and low intensity pulsed ultrasound was initially established, which provided a theoretical basis for further study of axon regeneration, and also new ideas for action of low intensity pulsed ultrasound on axon regeneration regulatory pathway. [ABSTRACT FROM AUTHOR]

• LIPUS can directly impact the intracellular dynamics of macromolecules. • The diffusivities of cytoplasmic macromolecules increase during LIPUS exposure. • LIPUS stimulation accelerates passive nucleocytoplasmic transport. • The ERK activity can be amplified by its increased diffusivity under LIPUIS exposure. Whilst a number of studies have demonstrated that low-intensity pulsed ultrasound (LIPUS) is a promising therapeutic ultrasound technique that can be used for delivering mild mechanical stimuli to target tissue non-invasively, the underlying biophysical mechanisms still remain unclear. Most mechanism studies have focused explicitly on the effects of LIPUS on the cell membrane and mechanosensitive receptors. In the present study, we propose an additional mechanism by which LIPUS propagation through living cells may directly impact intracellular dynamics, particularly the diffusion transport of biomolecules. To support our hypothesis, human epithelial-like cells (SaOS-2 and HeLa) seeded on a confocal dish placed on a microscope stage were exposed to LIPUS with various exposure conditions (ultrasound frequencies of 0.5, 1 and 3 MHz, peak acoustic pressure of 200 and 400 kPa, a pulse repetition frequency of 1 kHz and a 20 % duty cycle), and the diffusivities of various sizes of biomolecules in the cytoplasm area were measured using fluorescence recovery after photobleaching (FRAP). Furthermore, giant unilamellar vesicles (GUVs) filled with macromolecules were used to examine the physical causal relationship between LIPUS and molecular diffusion changes. Nucleocytoplasmic transport coefficients were also measured by modified FRAP that bleaches the whole cell nuclear region. Extracellular signal-regulated kinases (ERK) activity (the phosphorylation dynamics) was monitored using fluorescence resonance energy transfer (FRET) microscopy. All the measurements were taken during, before and after the LIPUS exposure. Our experimental results clearly showed that the diffusion coefficients of macromolecules within the cell increased with acoustic pressure by 12.1 to 33.5 % during the sonication, and the increments were proportional to their molecular sizes regardless of the ultrasound frequency used. This observation in living cells was consistent with the GUVs exposed to the LIPUS, which indicated that the diffusivity increase was a passive physical response to the acoustic energy of LIPUS. Under the 1 MHz LIPUS exposure with 400 kPa, the passive nucleocytoplasmic transport of enhanced green fluorescent protein (EGFP) was accelerated by 21.4 %. With the same LIPUS exposure condition, both the diffusivity and phosphorylation of ERK induced by EGF treatment were significantly elevated simultaneously, which implied that LIPUS could also modify the kinase kinetics in the signal transduction process. Taken together, this study is the first attempt to uncover the physical link between LIPUS and the dynamics of intracellular macromolecules and related biological processes that LIPUS can possibly increase the diffusivity of intracellular macromolecules, leading to the changes in the basic cellular processes: passive nucleocytoplasmic transport and ERK. Our findings can provide a novel perspective that the mechanotransduction process that the intracellular region, in addition to the cell membrane, can convert the acoustic stimuli of LIPUS to biochemical signals. [ABSTRACT FROM AUTHOR]