Low-intensity Pulsed Ultrasound Group Research Articles

Evaluation of Low-Intensity Pulsed Ultrasound on Stress Fractures to Reduce the Time to Return to Sport or Activity in the Physically Active Population: A Systematic Review.

Stress fractures are a common and significant source of pain and burden that can require long periods of rest from physical activity to allow adequate healing. Specifically in athletes or those with physically demanding occupations, the prolonged period of rest and the potential for requiring surgical intervention in the case of poor or delayed healing can have devastating impacts on these individuals' careers and socioeconomic well-being. In this population, successful healing, in addition to a quicker healing time and a sooner return to activity, are important outcomes when faced with treating stress fractures. The use of low-intensity pulsed ultrasound (LIPUS) to accelerate bone healing has been a topic of investigation, though little research has explored the use of LIPUS specifically in the physically active population. The purpose of this study was to review the existing literature on the use of LIPUS for stress fracture healing in the physically active population with the outcome of a quicker return to sport or physical duties. The PubMed and Embase databases were screened for relevant articles using defined Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Two independent researchers screened articles using PICOS criteria for inclusion in the review. Data were independently extracted regarding study and population characteristics as well as outcome measures, including time to healing of fractures and time to return to sport or physical activity. Five studies were ultimately included in the systematic review. One study investigated the use of LIPUS in pediatric athletes with spondylolysis, while four studies investigated lower extremity stress fractures in adult populations. All reported the outcomes of either rate or time to healing and ability to return to sport or activity. One study found a statistically significant improvement in the rate of bone union in the intervention group undergoing LIPUS compared to the control. Two studies found a statistically significant decrease in the time to resolution of symptoms, allowing an earlier return to sport or physical duties. Two studies found no difference in the time to healing or success rate of healing between the LIPUS group and the control group. This review of the literature suggests that the use of LIPUS for the treatment of stress fractures in the athletic or physically active population has the potential to expedite the resolution of symptoms and return to activity. Due to the heterogeneity of the existing studies, more research is needed to definitively determine the most appropriate clinical application of LIPUS and its most effective ultrasound settings. Further research should be directed toward more controlled studies specifically investigating the athletic and physically active population.

Transcriptome profile analysis revealed the potential mechanism of LIPUS treatment for Adriamycin-induced chronic kidney disease rat

BackgroundDeveloping 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. MethodsThe 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. ResultsLIPUS 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. ConclusionContinuous 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.

Inhibitory effect of low-intensity pulsed ultrasound on apoptosis of splenic lymphocytes in septic rats

To investigate the inhibitory effect of low- intensity pulsed ultrasound (LIPUS) on apoptosis of splenic lymphocytes in rats with sepsis and explore its possible mechanism. Seventy-eight female SD rats were randomly divided into LIPUS group, cecal ligation and puncture (CLP) group and sham-operated group (Sham) (n=26), and in the former two groups, rat model of sepsis were established by CLP. Immediately after the operation, the rats in LIPUS group received pulsed ultrasound therapy with an ultrasound intensity of 200 mW/cm2, irradiation time of 20 min, and frequency of 0.37 MHz. The survival of the rats in each group was observed within 72 h after CLP. The changes in splenic lymphocyte counts were observed using HE staining, and apoptosis of the splenic lymphocytes was detected using TUNEL assay and flow cytometry. The expression levels of Bcl-2, Bcl2-associated X protein (Bax) and caspase-3 were detected by immunohistochemistry, Western blotting and RT-qPCR. All the rats in the sham-operated group survived for over 72 h. The survival rates of the rats was significantly higher in LIPUS group than in CLP group (P<0.05). Compared with those in CLP group, the apoptosis rate of the splenic lymphocytes in LIPUS group was significantly decreased (P<0.05), the protein and mRNA expression levels of Bcl-2 were increased (P<0.05), and the protein and mRNA expression levels of Bax and caspase-3 were decreased (P<0.05). LIPUS inhibits apoptosis of splenic lymphocytes in septic SD rats possibly by regulating the key molecules in the mitochondrial pathway, thereby improving the survival rate and prolonging the survival time of the rats.

Effect of Novel Low-intensity Pulsed Ultrasound Stimulation on Accelerated Implant Osteointegration in Canine.

To evaluate the effect of low-intensity pulsed ultrasound (LIPU) application on dental implant accelerated osseointegration in the two-stage implant protocol. A total of 20 implants were placed in 10 mature mongrel dogs, two implants for each dog replacing the lower 3rd premolars bilaterally. After 3 months of extraction, implants were placed. After 24 hours of implantation, the right sides received LIPU for 20 mins/day, continuously for 20 days. The left sides didn't receive LIPU (control). Standardized radiographs were taken before LIPU and after 10 and 20 days for both sides. After 20 days of LIPU application, second-stage surgery was performed and provisional crowns were placed on each implant. Implants were subjected to functional occlusal loading for 4 weeks. Standardized radiographs were taken after 2 and 4 weeks of loading and analyzed to assess the peri-implant bone density changes. All data were collected, tabulated, and statistically analyzed. All tissues appeared clinically normal, with the absence of inflammation and peri-implant radiolucency. The survival rate was 100%. The LIPU group showed a statistically significantly higher percentage increase in mean bone density after 10 LIPU sessions, 20 LIPU sessions, and 2 and 4 weeks of loading, than a control group. The LIPU stimulation radiographically increased the bone density around implant area and accelerated osseointegration in the two-stage implant protocol. Low-intensity pulsed ultrasound stimulation could be beneficial in accelerating osseointegration and thus shortening the waiting period for final prosthetic delivery.

Therapeutic Myogenesis Induced by Ultrasound Exposure in a Volumetric Skeletal Muscle Loss Injury Model

Background: Low-intensity pulsed ultrasound (LIPUS) irradiation has been shown to induce various responses in different cells. It has been shown that LIPUS activates extracellular signal–regulated kinase 1/2 (ERK1/2) through integrin. Purpose: To study the effects of LIPUS on myogenic regulatory factors and other related myogenesis elements in a volumetric skeletal muscle loss injury model. Study Design: Controlled laboratory study. Methods: C57BL/6J mice were subjected to full-thickness muscle defect injury of the quadriceps and treated with direct application of LIPUS 20 min/d or non-LIPUS treatment (control) for 3, 7, and 14 days. LIPUS was also applied to C2C12 cells in culture in the presence of low and high doses of lipopolysaccharides. The expression levels of myogenic regulatory factors and the expression levels of myokine-related and angiogenic-related proteins of the control and LIPUS groups were analyzed. Results: Muscle volume in the injury site was restored at day 14 with LIPUS treatment. Paired-box protein 7, myogenic factor 5, myogenin, and desmin expressions were significantly different between control and LIPUS groups at days 7 and 14. Myokine and angiogenic cytokine-related factors were significantly increased in the LIPUS group at day 3 and decreased with no significant difference between the groups by day 14. LIPUS induced different responses of myogenic regulatory factors in C2C12 cells with low and high doses of lipopolysaccharides. LIPUS promoted myogenesis through short-lived increase in interleukin-6 and heme oxygenase 1, together with activation of ERK1/2. Conclusion: LIPUS had a constant effect on the variables of tissue damage, from macrotrauma to microtrauma, leading to efficient muscle regeneration. Clinical Relevance: The focus of therapeutic strategies with LIPUS has been not only for microvascular regeneration but also for skeletal muscle and related local tissue recovery from acute or chronic damage.

Low-intensity pulsed ultrasound mitigates cognitive impairment by inhibiting muscle atrophy in hindlimb unloaded mice.

Microgravity leads to muscle loss, usually accompanied by cognitive impairment. Muscle reduction was associated with the decline of cognitive ability. Our previous studies showed that low-intensity pulsed ultrasound (LIPUS) promoted muscle hypertrophy and prevented muscle atrophy. This study aims to verify whether LIPUS can improve cognitive impairment by preventing muscle atrophy in hindlimb unloaded mice. In this study, mice were randomly divided into normal control (NC), hindlimb unloading (HU), hindlimb unloading + LIPUS (HU+LIPUS) groups. The mice in the HU+LIPUS group received a 30 mW/cm2 LIPUS irradiation on gastrocnemius for 20 min/d. After 21 days, LIPUS significantly prevented the decrease in muscle mass and strength caused by tail suspension. The HU+LIPUS mice showed an enhanced desire to explore unfamiliar environments and their spatial learning and memory abilities, enabling them to quickly identify differences between different objects, as well as their social discrimination abilities. MSTN is a negative regulator of muscle growth and also plays a role in regulating cognition. LIPUS significantly inhibited MSTN expression in skeletal muscle and serum and its receptor ActRIIB expression in brain, upregulated AKT and BDNF expression in brain. Taken together, LIPUS may improve the cognitive dysfunction in hindlimb unloaded rats by inhibiting muscle atrophy through MSTN/AKT/BDNF pathway.

A novel therapeutic approach of ultrasound stimulation to restore forelimb functions following cervical cord injury in rats

Low-intensity pulsed ultrasound (LIPUS) stimulation has shown promising results in neurorehabilitation following a traumatic injury in brain and peripheral nerves. However, the effects of LIPUS stimulation in the injured neural circuit after spinal cord injury (SCI) are still unknown. We investigated the effects of LIPUS on forelimb functions in chronic cervical cord injured rats with and without a serotonergic agonist drug, Buspirone treatment. Twenty-six rats were trained for forelimb reaching and grasping followed by C4 dorsal funiculi crush injury. To deliver LIPUS, a silicon-coated ultrasound disc was implanted above the cervical cord and electromyography electrodes were implanted into forelimb muscles. In two cohorts (LIPUS and LIPUS + Buspirone combined) rats were tested pre-, with- and post-ultrasound stimulation. In LIPUS group rats, fore-limb reaching and grasping success rates first increased and then dropped after 3 weeks while for combination of drug and LIPUS stimulation the score continued to increase. Furthermore, LIPUS stimulation alone did not result in any significant improvement of grip strength compared to the control and combined groups. The findings of this study indicated the potential of LIPUS in SCI recovery and offer a future research direction of a new neuromodulation method.

Low-intensity pulsed ultrasound reduces lymphedema by regulating macrophage polarization and enhancing microcirculation.

Background: Conventional therapies reduce lymphedema but do not cure it because they cannot modulate the pathophysiology of secondary lymphedema. Lymphedema is characterized by inflammation. We hypothesized that low-intensity pulsed ultrasound (LIPUS) treatment could reduce lymphedema by enhancing anti-inflammatory macrophage polarization and microcirculation. Methods: The rat tail secondary lymphedema model was established through the surgical ligation of lymphatic vessels. The rats were randomly divided into the normal, lymphedema, and LIPUS treatment groups. The LIPUS treatment (3min daily) was applied 3days after establishing the model. The total treatment period was 28days. Swelling, fibro adipose deposition, and inflammation of the rat tail were evaluated by HE staining and Masson's staining. The photoacoustic imaging system and laser Doppler flowmetry were used to monitor microcirculation changes in rat tails after LIPUS treatment. The cell inflammation model was activated with lipopolysaccharides. Flow cytometry and fluorescence staining were used to observe the dynamic process of macrophage polarization. Results: After 28days of treatment, compared with the lymphedema group, the tail circumference and subcutaneous tissue thickness of rats in the LIPUS group were decreased by 30%, the proportion of collagen fibers and the lymphatic vessel cross-sectional area was decreased, and tail blood flow was increased significantly. Cellular experiments revealed a decrease in CD86+ macrophages (M1) after LIPUS treatment. Conclusion: The transition of M1 macrophage and the promotion of microcirculation could be responsible for the beneficial effect of LIPUS on lymphedema.

Effect of low-intensity pulsed ultrasound on osteogenic differentiation of human induced membrane-derived cells in Masquelet technique

IntroductionThe Masquelet technique is a relatively new method for large bone defect treatment. In this technique, grafted bone tissue is used, and after the cement is removed, the induced membrane (IM; that form around the cement spacers placed in the bone defect region) is thought to play an important role in promoting bone formation. On the other hand, low-intensity pulsed ultrasound (LIPUS) is known to promote fracture healing and angiogenesis through mechanical stimulation. This study aimed to investigate the in vitro effects of LIPUS on the osteogenic differentiation of human induced membrane-derived cells (IMCs). MethodsSeven patients who had been treated using the Masquelet technique were enrolled. The IM was harvested during the second stage of the technique. IMCs were isolated, cultured in growth medium, and then divided into two groups: (1) control group, IMCs cultured in osteogenic medium without LIPUS, and (2) LIPUS group, IMCs cultured in osteogenic medium with LIPUS treatment. Adherent cells from the IM samples were harvested after the first passage and evaluated for cell surface protein expression using immunostaining. A cell proliferation assay was used to count the number of IMCs using a hemocytometer. Osteogenic differentiation capability was assessed using an alkaline phosphatase (ALP) activity assay, Alizarin Red S staining, and real-time reverse transcription-polymerase chain reaction. ResultsCell surface antigen profiling revealed that the IMCs contained cells positive for the mesenchymal stem cell–related markers CD73, CD90, and CD105. No significant difference in cell numbers was found between the control and LIPUS groups. The ALP activity of IMCs in the LIPUS group was significantly higher than that in the control group on days 7 and 14. Alizarin red S staining intensity was significantly higher in the LIPUS group than in the control group on day 21. Runx2 and VEGF expression was significantly upregulated on days 7 and 14, respectively, compared with levels in the control group. ConclusionWe demonstrated the significant effect of LIPUS on the osteogenic differentiation of human IMCs. This study indicates that LIPUS can be used as an additional tool for the enhancement of the healing process of the Masquelet technique.

THE ROLE OF DENTIN MATRIX PROTEIN 1 (DMP1) IN LIPUS-ACCELERATED OSTEOPOROTIC FRACTURE HEALING

Osteoporotic fracture has become a major problem in ageing population and often requires prolonged healing time. Low Intensity Pulsed Ultrasound (LIPUS) can significantly enhance fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). DMP1 in osteocytes is responsible for maintaining LCN and mineralisation. This study aims to investigate osteocyte-specific DMP1's role in enhanced osteoporotic fracture healing in response to mechanical stimulation.Bilateral ovariectomy was performed in 6-month-old female SD rats to induce osteoporosis. Metaphyseal fracture was created at left distal femur using oscillating micro-saw. Rats were randomised to groups: (1) DMP1 KD, (2) DMP1 KD + LIPUS, (3) Control, or (4) Control + LIPUS, where KD stands for knockdown by injection of shRNA into marrow cavity 2 weeks before surgery. Assessments included weekly radiography, microCT and immunohistochemistry on DMP1, E11, FGF23 and sclerostin.DMP1 KD significantly impaired LIPUS-accelerated fracture healing when comparing KD + LIPUS group to Control + LIPUS group. The X-ray relative opacity showed less tissue growth at all timepoints (Week 1, 3 &amp; 6; p=0.000, 0.001 and 0.003 respectively) and the bone volume fraction was decreased after DMP1 KD at Week 3 (p=0.006). DMP1 KD also significantly altered the expression levels of osteocyte-specific DMP1, E11, FGF23 and sclerostin during healing process.The lower relative opacity and bone volume fraction in DMP1 KD groups indicated that knockdown of DMP1 was associated with poorer fracture healing process compared to non-knockdown groups. The similar results between knockdown group with and without LIPUS showed that blockage of DMP1 would negate LIPUS-induced enhancement on fracture healing.Acknowledgment: General Research Fund (Ref: 14113018)

Low-intensity pulsed ultrasound and parathyroid hormone improve muscle atrophy in estrogen deficiency mice

Due to aging and long-term estrogen deficiency, postmenopausal women suffer muscle atrophy (MA), which is characterized by decreased muscle mass and muscle quality. Low-intensity pulsed ultrasound (LIPUS) is an acoustic wave inducing biological effects mainly by the mechanical stimulation and used as a non-invasive physical therapy for muscle repair. Parathyroid hormone (PTH) is an 84-amino-acid polypeptide, and its bioactive fragment [PTH (1–34)] has potential application in the treatment of MA. We speculate that the combination of physical therapy (i.e., the LIPUS) and regulatory hormone (i.e., the PTH) would be more effective in the treatment of MA. The objective of this study was to evaluate the individual and combined effects of LIPUS and PTH therapy on MA in estrogen deficiency mice. Seventy 8-week-old female C57BL/6J mice were used in this study and the MA model was induced by an intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD) for 20 consecutive days. The VCD-induced MA mice were randomly divided into MA, LIPUS, PTH and LIPUS + PTH (Combined) groups (n = 10/group). In the LIPUS group, the mice were treated by LIPUS in bilateral quadriceps muscles for 20 min, five times a week for 6 weeks. In the PTH group, the mice received subcutaneous injection of PTH (1–34) (80 ug/kg/d) five times a week, for 6 weeks. In the Combined group, the PTH was administrated 30 min before each LIPUS session. Hematoxylin-eosin (H&E) staining, serum biochemical analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to evaluate the therapeutic effects of related treatments. The results showed that the MA mice had a disordered estrus cycle, significantly decreased muscle mass and myofibers cross-sectional area (CSA). After treatments, LIPUS, PTH and Combined groups had a significantly increased CSA, compared with the MA mice without treatment. In addition, Combined group had a significantly increased mRNA expression of Pax7, MyoD and MyoG, compared with LIPUS and PTH monotherapy groups. Our findings indicated that the combination of LIPUS and PTH treatment improves muscle regeneration ability, which might have potential for treating MA in postmenopausal women.

Low-intensity pulsed ultrasound ameliorates erectile dysfunction induced by bilateral cavernous nerve injury through enhancing Schwann cell-mediated cavernous nerve regeneration.

Cavernous nerve injury-induced erectile dysfunction caused by pelvic surgery or trauma is refractory to conventional medications and required an alternative treatment. Low-intensity pulsed ultrasound is a noninvasive mechanical therapy that promotes nerve regeneration. To investigate the therapeutic effect and potential mechanism of low-intensity pulsed ultrasound in the treatment of neurogenic erectile dysfunction. Thirty rats were randomly divided into the sham-operated group, bilateral cavernous nerve injury group, and bilateral cavernous nerve injury + low-intensity pulsed ultrasound group. The erectile function was assessed 3weeks after daily low-intensity pulsed ultrasound treatment. The penile tissues and cavernous nerve tissues were harvested and subjected to histologic analysis. Primary Schwann cells and explants were extracted from adult rats. The effects of low-intensity pulsed ultrasound on proliferation, migration, and nerve growth factor expression of Schwann cells and axonal elongation were examined in vitro. RNA sequencing and western blot assay were applied to predict and verify the molecular mechanism of low-intensity pulsed ultrasound-induced Schwann cell activation. Our study showed that low-intensity pulsed ultrasound promoted Schwann cells proliferation, migration, and neurotrophic factor nerve growth factor expression. Meanwhile, low-intensity pulsed ultrasound exhibits a stronger ability to enhance Schwann cells-mediated neurite outgrowth of major pelvic ganglion neurons and major pelvic ganglion/cavernous nerve explants in vitro. In vivo experiments demonstrated that the erectile function of the rats in the bilateral cavernous nerve injury + low-intensity pulsed ultrasound group was significantly higher than those in the bilateral cavernous nerve injury groups. Moreover, the expression levels of smooth muscle and cavernous endothelium also increased significantly in the bilateral cavernous nerve injury + low-intensity pulsed ultrasound group. In addition, we observed the higher density and number of cavernous nerve regenerating axons in the bilateral cavernous nerve injury + low-intensity pulsed ultrasound group, indicating that low-intensity pulsed ultrasound promotes axonal regeneration following cavernous nerve injury in vivo. RNA sequencing analysis and bioinformatic analysis suggested that low-intensity pulsed ultrasound might trigger the activation of the PI3K/Akt pathway. Western blot assay confirmed that low-intensity pulsed ultrasound activated Schwann cells through TrkB/Akt/CREB signaling. Low-intensity pulsed ultrasound promoted nerve regeneration and ameliorated erectile function by enhancing Schwann cells proliferation, migration, and neurotrophic factor nerve growth factor expression. The TrkB/Akt/CREB axis is the possible mechanism of low-intensity pulsed ultrasound-mediated Schwann cell activation. Low-intensity pulsed ultrasound-based therapy could be a novel potential treatment strategy for cavernous nerve injury-induced neurogenic erectile dysfunction.

Impact of low intensity pulsed ultrasound on volumetric root resorption of maxillary incisors in patients treated with clear aligner therapy: A retrospective study.

The aim of this study was to evaluate the volumetric root resorption in maxillary incisors following clear aligner therapy (CAT) with low-intensity pulsed ultrasound (LIPUS), and compare the results to CAT alone. This retrospective study evaluated pretreatment (T0) and post-treatment (T1) cone-beam computed tomography imaging of 42 adult patients. Twenty-one patients (14 females, 7 males, mean age= 38.1±12.96 years) were treated using CAT with LIPUS device, whereas the other twenty-one matching controls patients (15 females, 6 males, mean age= 35.6±11.7 years) were treated using CAT alone. Images were analyzed and a segmentation protocol was applied on the maxillary incisors. Each segmented tooth volume was exported as a surface mesh in the Visualization Toolkit (VTK) file format. The VTK files for all maxillary incisors were coded and corresponding teeth volumes from T0 and T1 were superimposed. Clipping the crown of each tooth was done, then measurements of root volumes and differences between groups were performed. Changes in root volumes were assessed (p<0.05). Root loss was evident in all teeth in both groups, but was significantly increased in all maxillary incisors of the control group (p<0.001) and in upper left central incisor of LIPUS group (p=0.009). When both groups were compared, there was statistically significant minimal volumetric root loss in LIPUS group (3.50-7.32 mm3), when compared to control group (11.48-12.95 mm3) (p<0.05). LIPUS group showed less volumetric root resorption compared to control group during the studied treatment time using clear aligners.

Effects of low-intensity pulsed ultrasound on the infrapatellar fat pad in knee osteoarthritis: a randomized, double blind, placebo-controlled trial.

[Purpose] We investigated the effects of low-intensity pulsed ultrasound (LIPUS) irradiation of the infrapatellar fat pad (IFP) combined with therapeutic exercise for management of knee osteoarthritis (knee OA). [Participants and Methods] The study included 26 patients with knee OA, who were randomized into the LIPUS group (patients underwent LIPUS + therapeutic exercise) and the therapeutic exercise group (patients underwent sham LIPUS + therapeutic exercise). We measured changes in the patellar tendon-tibial angle (PTTA) and in IFP thickness, IFP gliding, and IFP echo intensity after 10 treatment sessions to determine the effects of the aforementioned interventions. We additionally recorded changes in the visual analog scale, Timed Up and Go Test, the Western Ontario and McMaster Universities Osteoarthritis Index, and Kujala scores, as well as range of motion in each group at the same end-point. [Results] Compared with patients in the therapeutic exercise group, those in the LIPUS group showed significant post-treatment improvements in PTTA, VAS, and Kujala scores, as well as in range of motion. [Conclusion] The combined use of LIPUS irradiation of the IFP and therapeutic exercise is a safe and effective modality to reduce IFP swelling, relieve pain, and improve function in patients with knee OA.

Low-intensity pulsed ultrasound irradiation attenuates collagen degradation of articular cartilage in early osteoarthritis-like model mice

PurposeOsteoarthritis (OA) is a combination of degeneration and destruction of articular cartilage due to mechanical stress, secondary synovitis, and bone remodelling. In recent years, early knee OA, a preliminary stage of structural failure in OA, has attracted attention as a potential target for therapy to prevent the onset of OA. Intra-articular administration of monoiodoacetic acid (MIA) induces OA-like symptoms, and low doses of MIA induce early OA like symptoms. In this experiment, a low-dose of MIA was induced to early OA model mice, which were then irradiated with low-intensity pulsed ultrasound (LIPUS) to examine whether LIPUS improves symptoms of early OA.MethodsAfter 4 weeks of LIPUS irradiation, articular cartilage was observed at 1 and 4 weeks. The Osteoarthritis Research Society International (OARSI) scores were calculated using Safranin-O staining results. Cartilage degeneration was detected using Denatured Collagen Detection Reagent (DCDR).ResultsWe observed a significant decrease in OARSI scores in the LIPUS irradiated group at week 4. The non-LIPUS group showed widespread areas of double positivity for Type II collagen and DCDR, whereas the LIPUS group showed only a small number of DCDR-positive areas. In addition, macrophage numbers counted in the articular capsule at week 1 showed a significant decrease in the LIPUS irradiated group. Lubricin detection showed that lubricin positive cell number was significantly increased by LIPUS irradiation at week 4.ConclusionsThese results suggest that LIPUS attenuates cartilage degeneration in early OA by relieving inflammation and enhancing the inhibitory effect of lubricin on cartilage degeneration.

Evaluation of Efficacy of Low-Intensity Pulsed Ultrasound on Comorbidities Following Mandibular Impacted Third Molar Surgery: A Prospective Study.

Despite several in vitro and in vivo applications of low-intensity pulsed ultrasound (LIPUS), it remains an under-studied feature of the oral and maxillofacial region. The goal of this in vivo study was to objectively investigate the efficacy of low-intensity pulsed ultrasound on wound healing and related morbidities following surgical removal of an impacted third molar. The following in vivo prospective, comparative, randomised controlled clinical study was carried out amongst 56 patients who reported to the Department of Oral and Maxillofacial Surgery fulfilling the inclusion criteria. Group A received sham ultrasound, whereas Group B received LIPUS therapy. Based on the group allocated LIPUS 1 MHz, pulsed 20% and dose 1.0 watts/square centimetre (W/cm2)/sham, ultrasound therapy was given on 1st, 2nd and 3rd post-operative days. The assessment of post-operative pain, oedema, trismus and wound healing on preoperative, first, third and seventh postoperative days. The quantitative variables of the study were assessed using independent sample t-test, and qualitative variables were assessed using the Chi-square test. The P < 0.05 on third and seventh post-op days for pain, trismus and wound healing in the LIPUS group compared to control group making it statistically significant. There was no statistically significant difference in the reduction of oedema amongst the two groups. Post-LIPUS application in the patients, postoperative pain was significantly reduced, trismus was noticeably improved and wound healing was satisfactory and can be employed as a complementary technique.

Low-intensity pulsed ultrasound does not promote bone healing and functional recovery after open wedge high tibial osteotomy.

To evaluate whether low-intensity pulsed ultrasound (LIPUS) accelerates bone healing at osteotomy sites and promotes functional recovery after open-wedge high tibial osteotomy (OWHTO). Overall, 90 patients who underwent OWHTO without bone grafting were enrolled in this nonrandomized retrospective study, and 45 patients treated with LIPUS were compared with 45 patients without LIPUS treatment in terms of bone healing and functional recovery postoperatively. Clinical evaluations, including the pain visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score, were performed preoperatively as well as six weeks and three, six, and 12 months postoperatively. The progression rate of gap filling was evaluated using anteroposterior radiographs at six weeks and three, six, and 12 months postoperatively. The pain VAS and JOA scores significantly improved after OWHTO in both groups. Although the LIPUS group had better pain scores at six weeks and three months postoperatively, there were no significant differences in JOA score between the groups. The lateral hinge united at six weeks postoperatively in 34 (75.6%) knees in the control group and in 33 (73.3%) knees in the LIPUS group. The progression rates of gap filling in the LIPUS group were 8.0%, 15.0%, 27.2%, and 46.0% at six weeks and three, six, and 12 months postoperatively, respectively, whereas in the control group at the same time points they were 7.7%, 15.2%, 26.3%, and 44.0%, respectively. There were no significant differences in the progression rate of gap filling between the groups. The present study demonstrated that LIPUS did not promote bone healing and functional recovery after OWHTO with a locking plate. The routine use of LIPUS after OWHTO was not recommended from the results of our study. Cite this article: Bone Jt Open2022;3(11):885-893.

Role of low-intensity pulsed ultrasound in regulating macrophage polarization to accelerate tendon-bone interface repair.

Low-intensity pulsed ultrasound (LIPUS) has been proven to accelerate the healing of the tendon-bone interface (TBI), and macrophages are considered to play an important regulatory role. This study was designed to explore the polarization of macrophages during treatment of TBI injury with LIPUS. In a rat model of rotator cuff tear, LIPUS or mock sonication (controls) was administered from 1 week postoperatively. The supraspinatus-supraspinatus tendon-humerus complexes were harvested for further evaluation at different time points for measures such as new bone formation, TBI maturity, ultimate failure load and stiffness, and types of macrophages. In vitro, bone marrow-derived macrophageswere cultured, and polarization was identified after stimulation with or without LIPUS (the LIPUS or control groups, respectively). Two weeks posttreatment, the LIPUS group showed higher bone volume/total volume ratios and better TBI maturity scores. Six weeks posttreatment, the failure load of the LIPUS group was significantly higher than that of the control group. LIPUS also accelerated initial inflammatory macrophage accumulation and facilitated anti-inflammatory macrophage polarization (M2) in the late period. In the in vitro macrophage polarization model, the LIPUS group showed a higher proportion of M2 macrophages and mRNA expression of anti-inflammatory genes than the control group, while there was no significant difference in the proinflammatory macrophages between the two groups. Our observations revealed that macrophage polarization may be a potential mechanism of LIPUS treatment for TBI repair.

Low-Intensity Pulsed Ultrasound Enhanced Adipose-Derived Stem Cell-Mediated Angiogenesis in the Treatment of Diabetic Erectile Dysfunction through the Piezo-ERK-VEGF Axis.

Objectives Erectile dysfunction is a major comorbidity of diabetes. Stem cell transplantation is a promising method to treat diabetic erectile dysfunction. In this study, we evaluated whether low-intensity pulsed ultrasound (LIPUS) could enhance the efficacy of adipose-derived stem cells (ADSCs) and investigated the underlying molecular mechanism. Materials and methods. Sixty 8-week-old male Sprague–Dawley rats were randomly divided into the normal control (NC) cohort or the streptozocin-induced diabetic ED cohort, which was further subdivided into DM, ADSC, LIPUS, and ADSC+LIPUS groups. Rats in the ADSC or ADSC+LIPUS group received ADSC intracavernosal injection. Rats in the LIPUS or ADSC+LIPUS group were treated with LIPUS. The intracavernous pressure (ICP) and mean arterial pressure (MAP) were recorded at Day 28 after injection. The corpus cavernosum tissues were harvested and subjected to histologic analysis and ELISA. The effects of LIPUS on proliferation and cytokine secretion capacity of ADSCs were assessed in vitro. RNA sequencing and bioinformatic analysis were applied to predict the mechanism involved, and western blotting and ELISA were used for verification. Results Rats in the ADSC+LIPUS group achieved significantly higher ICP and ICP/MAP ratios than those in the DM, ADSC, and LIPUS groups. In addition, the amount of cavernous endothelium and cGMP level also increased significantly in the ADSC+LIPUS group. In vitro experiments demonstrated that LIPUS promoted proliferation and cell cycle progression in ADSCs. The excretion of cytokines such as CXCL12, FGF2, and VEGF was also enhanced by LIPUS. Bioinformatic analysis based on RNA sequencing indicated that LIPUS stimulation might activate the MAPK pathway. We confirmed that LIPUS enhanced ADSC VEGF secretion through the Piezo-ERK pathway. Conclusion LIPUS enhanced the curative effects of ADSCs on diabetic erectile dysfunction through the activation of the Piezo-ERK-VEGF pathway. ADSC transplantation combined with LIPUS could be applied as a synergistic treatment for diabetic ED.

The Value of First-Order Features Based on the Apparent Diffusion Coefficient Map in Evaluating the Therapeutic Effect of Low-Intensity Pulsed Ultrasound for Acute Traumatic Brain Injury With a Rat Model.

PurposeIn order to evaluate the neuroprotective effect of low-intensity pulsed ultrasound (LIPUS) for acute traumatic brain injury (TBI), we studied the potential of apparent diffusion coefficient (ADC) values and ADC-derived first-order features regarding this problem.MethodsForty-five male Sprague Dawley rats (sham group: 15, TBI group: 15, LIPUS treated: 15) were enrolled and underwent magnetic resonance imaging. Scanning layers were acquired using a multi-shot readout segmentation of long variable echo trains (RESOLVE) to decrease distortion. The ultrasound transducer was applied to the designated region in the injured cortical areas using a conical collimator and was filled with an ultrasound coupling gel. Regions of interest were manually delineated in the center of the damaged cortex on the diffusion weighted images (b = 800 s/mm2) layer by layer for the TBI and LIPUS treated groups using the open-source software ITK-SNAP. Before analysis and modeling, the features were normalized using a z-score method, and a logistic regression model with a backward filtering method was employed to perform the modeling. The entire process was completed using the R language.ResultsDuring the observation time, the ADC values ipsilateral to the trauma in the TBI and LIPUS groups increased rapidly up to 24 h. After statistical analysis, the 10th percentile, 90th percentile, mean, skewness, and uniformity demonstrated a significant difference among three groups. The receiver operating characteristic curve (ROC) analysis shows that the combined LR model exhibited the highest area under the curve value (AUC: 0.96).ConclusionThe combined LR model of first-order features based on the ADC map can acquire a higher diagnostic performance than each feature only in evaluating the neuroprotective effect of LIPUS for TBI. Models based on first-order features may have potential value in predicting the therapeutic effect of LIPUS in clinical practice in the future.