Low-intensity Pulsed Ultrasound Group Research Articles

AB017. Experimental study of pulsed ultrasound in the treatment of stress urinary incontinence

Low intensity pulsed ultrasound (LIPUS) has shown its ability of restoring soft tissue injury in a number of studies, but little is known about its molecular mechanism. Recent studies reported the regulatory effect of LIPUS on stem cell activation. We investigated the possible therapeutic effect of LIPUS in a stress urinary incontinence (SUI) rat model and its influence on myogenic satellite cells. Fifty Sprague Dawley rats underwent vaginal distension and bilateral ovariectomy mimicking partum injury and menopause to construct SUI models, which were further randomized into 100 mW/cm2 LIPUS, 200mW/cm2 LIPUS, 300 mW/cm2 LIPUS and none-treatment control subgroups with ten rats per subgroup. Ten rats served as mock operation control. Here we found the leak point pressure and bladder capacity were restored in 200mW/cm2 LIPUS and 300 mW/cm2 LIPUS groups, but not in 100 mW/cm2 LIPUS group. More robust striated muscle regeneration was observed in 200mW/cm2 LIPUS group comparing with the SUI none-treatment group. Moreover, we found LIPUS activated the myodifferentiation of muscle satellite cells, which is correlated to p38 phosphorylation level. These results show LIPUS ameliorate the symptom of SUI and activate satellite cell myodifferentiation.

Clinical Experience of Low-Intensity Pulsed Ultrasound (LIPUS) in Scaphoid Fracture

Objective: The objective of this study was to investigate the clinical results of scaphoid fracture. Materials and Methods: The subjects were 13 patients (12 males, 1 female) with scaphoid fracture who underwent surgical (10 patients) or conservative (3 patients) therapy in our hospital from 2014 to 2017. Four patients (postoperative 3 and conservative 1) used low intensity pulsed ultrasound (LIPUS), and 9 patients (postoperative 7 and conservative 2) did not. We divided the patients into 2 groups: the LIPUS group (L group) and the non LIPUS (non L group). We evaluated the L group by Herbert classification, and both groups by the time to bone union and the time to start of therapy from injury. A Mann–Whitney test was used to analyze the time to start of therapy from injury between the L and non L groups. Results: Herbert classification in the L group was one each of types A, B, C, and D. Bone union had been achieved in all at the last consultation. The time to bone union in the 4 L group were 3, 6, 7 and 8 months. Patients in the non L group formed union by 3–4 months after start of therapy. The average time to start of therapy from injury was 3.5 months (L group) and 2.0 months (non L group), which was not statistically significantly different. Discussion: One case did not present until 12 months after injury, and this influenced our statistical results. The results suggest that we can expect adaptation of LIPUS in an increasing number of cases.

Effect of Low-Intensity Pulsed Ultrasound on Bone Healing at Osteotomy Sites After Open Wedge High Tibial Osteotomy

Objective: The purpose of this study was to evaluate the effects of low-intensity pulsed ultrasound (LIPUS) on bone healing at osteotomy sites after open wedge high tibial osteotomy (OWHTO). Materials and Methods: Fifty-four patients underwent OWHTO without bone grafting. Twenty-seven cases treated with LIPUS (group L) after surgery were compared with 27 cases without LIPUS treatment (group C). We divided the osteotomy gap into the lateral hinge and 4 zones on anteroposterior radiography, and the progression of gap filling was evaluated at 1, 3, and 6 months post-operatively in both groups. Results: In group L, the lateral hinge formed a union at 3 months postoperatively in 23 knees (85.2%). At 6 months, gap filling in 17 knees (63%) reached to zone 2. In group C, while the lateral hinge formed a union at 3 months postoperatively in 24 knees (88.9%). At 6 months, gap filling in 14 knees (51.9%) reached to zone 2. The progression of gap filling were 6.5%, 15.7%, and 29.1% (at 1, 3, and 6 months after surgery, respectively) in group L, while the progress levels at the same time points were 6.9%, 16.4%, and 27.3% in group C. There were no significant differences between the 2 groups. Discussion: LIPUS did not accelerate bone healing after OWHTO.

Low-intensity pulsed ultrasound promotes alveolar bone regeneration in a periodontal injury model

Periodontitis is a common oral disease characterized by progressive destruction of periodontal tissue and loss of teeth. However, regeneration of periodontal tissue is a time-consuming process. Low-intensity pulsed ultrasound (LIPUS) is a widely used non-invasive intervention for enhancing bone healing in fractures and non-unions. With the hypothesis that LIPUS may accelerate periodontal regeneration, the effects of LIPUS on periodontal tissue regeneration were investigated both in vitro and in vivo. LIPUS (90 mw/cm2, 20 min/d, 1.5 MHz) was applied to stimulate dog periodontal ligament cells (dPDLCS). The mRNA expression of BSP (P < 0.05), OPN (P < 0.05) and COL3 (P < 0.05) was increased significantly in the LIPUS group. The positive stained mineralized nodules by alizarin red in the LIPUS group were greater than in the control group (P < 0.05). Eight male beagle dogs were divided into 4 groups: guided tissue regeneration (GTR) group (G1), LIPUS + GTR group (G2), LIPUS group (G3), and control group (G4, no treatment). A 4 × 5 mm2 defect was created in the buccal alveolar bone. The modeling areas in the G2 and G3 groups were then exposed to LIPUS. Eight weeks after surgery, histological assessment indicated increased periodontal tissue in the LIPUS + GTR group. Micro computed tomography (micro-CT) showed that the regenerated bone volume (BV) in the G2 was significantly higher than that in the G1, G3 and G4 groups (P < 0.05). The bone surface (BS) trabecular number (Tb.N) and trabecular thickness (Tb.Th) in G2 were markedly higher than in G4 (P < 0.05). It is concluded that LIPUS + GTR can accelerate new alveolar bone formation, with a prospective for promoting periodontal tissue repair.

Effect of low level laser and low intensity pulsed ultrasound therapy on bone remodeling during orthodontic tooth movement in rats

BackgroundQuality bone regeneration, which leads to the improvement of bone remodeling, is essential for orthodontic treatment. In order to improve bone regeneration and increase the amount of tooth movement, different techniques have been implemented. The object of this study is to compare the effects of low-level laser therapy (LLLT), low-intensity pulsed ultrasound (LIPUS), and their combination on bone remodeling during orthodontic tooth movement.MethodsEighty (80) male, 6-week-old Sprague Dawley rats were grouped in to four groups, the first group was irradiated with (940 nm) diode laser, second group with LIPUS, and third group with combination of both LLLT and LIPUS. A forth group used was a control group in an incomplete block split-mouth design. The LLLT and LIPUS were used to treat the area around the moving tooth once a day on days 0–7, then the experiment was ended in each experimental endpoint (1, 3, 7, 14, and 21 days). For amount of tooth movement, models were imaged and analyzed. Histological examination was performed after staining with (hematoxylin and eosin) and (alizarin red and Alcian Blue) stain. One step reverse transcription-polymerase chain reaction RT-PCR was also performed to elucidate the gene expression of RANK, RANKL, OPG, and RUNX-2.ResultsThe amount of tooth movement, the histological bone remodeling, and the RT-PCR were significantly greater in the treatment groups than that in the control group. Among the treatment groups, the combination group was the highest and the LIPUS group was the lowest.ConclusionThese findings suggest that LLLT and LIPUS can enhance the velocity of tooth movement and improve the quality of bone remodeling during orthodontic tooth movement.

Effects of fibroblast growth factors 2 and low intensity pulsed ultrasound on the repair of knee articular cartilage in rabbits.

To investigate the effect of low intensity ultrasound irradiation combine with fibroblast growth factors (FGF2) on the repair of the knee articular cartilage and to explore its mechanism in rabbit. The model of the rabbit knee joint injury was established. 40 rabbits were divided into four groups, including control group, model group, FGF2 group and FGF2 + low intensity pulsed ultrasound group (FGF2 + LIPU). The knee joints of rabbits were taken at 4 and 8 weeks, respectively. Histopathological changes were detected by Hematoxylin and Eosin stain (HE) and evaluated by Wakitani score. The expression of FGF2 mRNA was detected by Real-time polymerase chain reaction (RT-PCR) and the levels of Collagen I and Collagen II protein were analyzed by Western blotting. In FGF2 group and FGF2 + LIPU group, it was found that the tissues of knee joint were gradually repaired following the change of time. Further, the recovery was better in FGF2 + LIPU group. Cartilage defect areas were filled with cartilage-like cells and the repair surface was fused with surrounding cartilage in FGF2 and FGF2 + LIPU groups. Wakitani scores were consistent with HE results. The expressions of FGF2 mRNA were higher in FGF2 and FGF2 + LIPU group than the model group. Western blotting results showed that the levels of Collagen I and Collagen II protein in FGF2 and FGF2 + LIPU groups were significantly increased compared with that in model group. FGF2 and LIPU combined application on the rabbit knees joint repair is better than FGF2 alone. FGF2 and LIPU combination can promote the synthesis and secretion of collagen in chondrocytes, promote the differentiation and maturation of chondrocytes during the repair of cartilage defects.

Effects of low-intensity pulsed ultrasound and pioglitazone on chondrocytes in osteoarthritis

Objective To investigate any protective effect of low-intensity pulsed ultrasound (LIPUS) and pioglitazone on chondrocytes in osteoarthritic patients using the pathway from peroxisome proliferator-activated γreceptor (PPARγ) to nuclear factor kappa B (NF-κB) to inducible nitric oxide synthase (iNOS). Methods Normal chondrocytes of 24 healthy adult New Zealand white rabbits were extracted and divided into a normal group, a lipopolysaccharide (LPS) group, a LIPUS group (LPS+ LIPUS) and a pioglitazone group (LPS+ pioglitazone), each of 6 using a random number table. Each group was given the intervention their names implies. The levels of tumor necrosis factor-α (TNF-α), leptin (LEP) and nitric oxide (NO) in the chondrocytes were detected using enzyme-linked immune sorbent assays. The expression of type II collagen (COL2) in the chondrocytes of each groups was detected using immunocytochemistry and fluorescent staining. The mRNA and protein expressions of PPARγ, NF-κB and iNOS were detected using reverse transcription polymerase chain reactions and western blotting respectively. Results Compared with the LPS group, the average level of TNF-α, LEP and NO in the LIPUS and pioglitazone groups was significantly lower, with the levels in the pioglitazone group significantly lower than in the LIPUS group. Compared with the LPS group, COL2 expression in the LIPUS group was significantly greater. The mRNA and protein expressions of PPARγ in the chondrocytes in the LIPUS and pioglitazone groups were significantly higher than those in the LPS group. Compared with the LPS group, the mRNA and protein expressions of NF-κB and iNOS in the pioglitazone and LIPUS groups were significantly lower, with the pioglitazone group′s levels significantly below those of the LIPUS group. Conclusion LIPUS and pioglitazone may promote anti-inflammatory action and COL2 synthesis in chondrocytes through the PPARγ/ NF-κB/iNOS pathway and play a protective role, at least in rabbits. Key words: Ultrasound; Pioglitazone; Osteoarthritis; Lipopolysaccharides

Effects of Low-Intensity Pulsed Ultrasound for Preventing Joint Stiffness in Immobilized Knee Model in Rats

The purpose of this study was to examine the effect of low-intensity pulsed ultrasound (LIPUS) in preventing joint stiffness. Unilateral knee joints were immobilized in two groups of rats (n = 6/period/group). Under general anesthesia, the immobilized knee joints were exposed to LIPUS for 20 min/d, 5 d/wk, using an existing LIPUS device (LIPUS group, 1.5-MHz frequency, 1.0-kHz repetition cycle, 200-µs burst width and 30-mW/cm2 power output) until endpoints (2, 4 or 6 wk). In the control group, general anesthesia alone was administered in the same manner as in the other group. The variables compared between the groups included joint angles; histologic, histomorphometric and immunohistochemical analyses; quantitative reverse transcription polymerase chain reactions; and tissue elasticity. LIPUS had a preventive effect on joint stiffness, resulting in decreased adhesion, fibrosis and inflammation and hypoxic response after joint immobilization.

Low-Intensity Pulsed Ultrasound Accelerates Traumatic Vertebral Fracture Healing by Coupling Proliferation of Type H Microvessels.

Patients with traumatic vertebral fractures often have major associated postoperative morbidities such as healing failure and kyphosis. Low-intensity pulsed ultrasound (US) has been found to promote bone fracture healing. The objectives of our study were to determine whether low-intensity pulsed US could promote traumatic vertebral fracture healing and to explore its inner mechanisms. A rat model of traumatic vertebral fracture was created and treated with low-intensity pulsed US after surgery. At 4 weeks after surgery, radiographic, micro-computed tomography, and 3-dimensional reconstruction were used to assess the radiologic healing status; a histologic analysis was performed to evaluate the pathologic process and relationship between osteogenesis and type H microvessels. Well-remodeled trabecular meshworks were found in the low-intensity pulsed US treatment group compared to the control group. Micro-computed tomography and 3-dimensional reconstruction revealed more and thicker trabeculae after low-intensity pulsed US treatment. Abundant chondrocytes, a newly formed bone marrow cavity, trabeculae, and microvessels were formed at the fracture sites. More osterix-positive osteoblasts were circling the newly formed bone meshwork and were situated at the interface of chondrocytes in the low-intensity pulsed US treatment group. Type H microvessels were spreading around the newly formed trabecula, bone marrow cavity, osteoblasts, and interface of chondrocytes, with a larger mean vascular density in the low-intensity pulsed US group. Low-intensity pulsed US could accelerate traumatic vertebral fracture healing by temporally and spatially increasing chondrogenesis and osteoblast-induced osteogenesis coupled with angiogenesis of type H microvessels in a rat model of traumatic vertebral fracture.

Low-intensity pulsed ultrasound promotes Schwann cell viability and proliferation via the GSK-3β/β-catenin signaling pathway.

Background: It has been reported that ultrasound enhances peripheral nerve regeneration, but the mechanism remains elusive. Low-intensity pulsed ultrasound (LIPUS) has been reported to enhance proliferation and alter protein production in various types of cells. In this study, we detected the effects of LIPUS on Schwann cells.Material and methods: Schwann cells were separated from new natal Sprague-Dawley rat sciatic nerves and were cultured and purified. The Schwann cells were treated by LIPUS for 10 minutes every day, with an intensity of 27.37 mW/cm2. After treatment for 5 days, MTT, EdU staining, and flow cytometry were performed to examine cell viability and proliferation. Neurotrophic factors, including FGF, NGF, BDNF, and GDNF, were measured by western blot and real-time PCR. GSK-3β, p-GSK-3β, β-catenin and Cyclin D1 protein levels were detected using a western blot analysis. The expression of Cyclin D1 was also detected by immunofluorescence.Results: MTT and EdU staining showed that LIPUS increased the Schwann cells viability and proliferation. Compared to the control group, LIPUS increased the expression of growth factors and neurotrophic factors, including FGF, NGF, BDNF, GDNF, and Cyclin D1. Meanwhile, GSK-3β activity was inhibited in the LIPUS group as demonstrated by the increased level of p-GSK-3β and the ratio of the p-GSK-3β/GSK-3β level. The mRNA and protein expressions of β-catenin were increased in the LIPUS group. However, SB216763, a GSK-3β inhibitor, reversed the effects of LIPUS on Schwann cells.Conclusion: LIPUS promotes Schwann cell viability and proliferation by increasing Cyclin D1 expression via enhancing the GSK-3β/β-catenin signaling pathway.

Low-intensity pulsed ultrasound stimulation for mandibular condyle osteoarthritis lesions in rats.

This study evaluated low-intensity pulsed ultrasound effects for temporomandibular joint osteoarthritis in adult rats. Osteoarthritis-like lesions were induced in 24 adult rats' temporomandibular joints with low-dose mono-iodoacetate injections. The rats were divided into four groups: control and mono-iodoacetate groups, injected with contrast media and mono-iodoacetate, respectively, at 12weeks and observed until 20weeks; and low-intensity pulsed ultrasound and mono-iodoacetate + low-intensity pulsed ultrasound groups, injected with contrast media and mono-iodoacetate, respectively, at 12weeks with low-intensity pulsed ultrasound performed from 16 to 20weeks. Condylar bone mineral density, bone mineral content and bone volume were evaluated weekly with microcomputed tomography. Histological and immunohistochemical staining for matrix metalloproteinases-13 was performed at 20weeks. At 20weeks, the mono-iodoacetate + low-intensity pulsed ultrasound group showed significantly higher bone mineral density, bone mineral content and bone volume than the mono-iodoacetate group; however, these values remained lower than those in the other two groups. On histological and immunohistochemical analysis, the chondrocytes were increased, and fewer matrix metalloproteinases-13 immunopositive cells were identified in the mono-iodoacetate + low-intensity pulsed ultrasound group than mono-iodoacetate group. Low-intensity pulsed ultrasound for 2weeks may have therapeutic potential for treating temporomandibular joint osteoarthritis lesions.

Effect of Low-Intensity Pulsed Ultrasound on the Expression of Calcium Ion Transport-Related Proteins during Tertiary Dentin Formation

Low-intensity pulsed ultrasound (LIPUS) is known for its positive effect on bone healing and reparative regeneration. This study investigated whether LIPUS affects reparative progression of the tooth and the expression of calcium ion transport-related proteins in odontoblasts and dental pulp cells using a rat dentin–pulp complex injury model. Forty male adult Sprague-Dawley rats underwent cavity preparation in the right maxillary first molar: 20 received LIPUS irradiation on the cavity-prepared tooth; 20 received LIPUS irradiation on the left maxillary first molar. Rats were randomly allocated into four groups: blank control group, LIPUS group, cavity-prepared group, cavity-prepared + LIPUS group. LIPUS irradiation (frequency: 1.5 MHz, 200-µs pulse width, 1-kHz pulse repetition frequency, 30 mW/cm2 spatial averaged temporal averaged intensity) was administered individually for 20 min daily. Rats were sacrificed 1, 3, 7 and 14 d post-operation. The histopathological and cellular morphologic changes in the dentin–pulp complex were detected with hematoxylin and eosin staining. Expression of calcium ion transport-related proteins (Cav1.2, NCX1 and TRPV1) was determined with immunohistochemical staining and imaging analysis. Histopathological analysis revealed obvious reparative dentin formation at day 14 in the cavity-prepared + LIPUS group compared with the other groups. Expression levels of Cav1.2, NCX1 and TRPV1 increased significantly by 22%, 53% and 23%, respectively, at day 1 and increased significantly by 23%, 27% and 22%, respectively, at day 3 in the cavity-prepared + LIPUS group (p < 0.05) compared with the cavity-prepared group. LIPUS has a positive effect on the expression of calcium transport-related proteins during early-stage dentin injury and facilitates tertiary dentin formation; the mechanism for this likely relates to the inflammatory reaction and a mechanical effect.

Effect of low intensity pulsed ultrasound on expression of TGF-β1 and Smads during dentin injury and repair

To explore the effect of low intensity pulsed ultrasound (LIPUS) on TGF-β1/Smad 2, 3 signal pathway during the dentin injury and repair. Methods: Among 25 Sprague-Dawley rats, 5 rats served as a blank control group without treatment. The remaining 20 rats received modified caries preparation inbilateral maxillary first molars to establish a model of dentin-pulp injury and repair. The right maxillary first molars served as a LIPUS group, which received LIPUS irradiation (frequency: 1.5 MHz, pulse width: 200 μs, pulse repetition frequency: 1 kHz, spatial averaged temporal averaged intensity: 30 mW/cm2, 20 min/d), and the left maxillary first molars served as a cavity-prepared group, which received fake LIPUS irradiation. The rats were sacrificed at 1, 3, 5, 7 and 14 days after LIPUS irradiation. Immunohistochemical staining and Image-pro plus 6.0 were applied to detect the expression and distribution of transforming growth factor-beta1 (TGF-β1) and small mothers against decapentaplegic 2/3(Smad 2 and Smad 3). Results: Immunohistochemical staining showed that the expression of TGF-β1 and Smad 2, 3 were low innormal pulp, but they were increased in different degree after dentin injury. The result of image analysis showed that the expression of TGF-β1 in the cavity-prepared group gradually increased at the first day and peaked at day 5, and then it returned to normal level at day 14. However, the expression of TGF-β1 in the LIPUS group were significantly higher than that in the cavity-prepared group at day 3 and 5 (both P<0.05). The expressions of Smad 2,3 in both the LIPUS group and the cavity-prepared group were consistently increased all the way, but the expressions in the LIPUS group were higher compared with that in the cavity-prepared group (P<0.05). Conclusion: The TGF-β1/Smad 2, 3 signal pathway can be activated during the dentin injury and repair. LIPUS can up-regulate the expression of TGF-β1 and Smad 2, 3 in the early period, which may take part in the dentin-pulp complex injury and repair process.

Effect of Low-Intensity Pulsed Ultrasound on Bone Healing at Osteotomy Sites After Open Wedge High Tibial Osteotomy.

The purpose of this study was to evaluate the effects of low-intensity pulsed ultrasound (LIPUS) on bone healing at osteotomy sites after open wedge high tibial osteotomy (OWHTO). Twenty-six patients underwent OWHTO without bone grafting. Thirty cases treated with LIPUS (group L) after surgery were compared with 13 cases without LIPUS treatment (group C). We divided the osteotomy gap into the lateral hinge and 4 zones on anteroposterior radiography, and the progression of gap filling was evaluated at 1, 3, and 6 months post-operatively in both groups. In group L, the lateral hinge formed a union at 3 months postoperatively in 11 knees (84.6%). At 6 months, gap filling in 10 knees (76.9%) reached to zone 2. In group C, while the lateral hinge formed a union at 3 months postoperatively in all cases. At 6 months, gap filling in 6 knees (46.1%) reached to zone 2. The progression of gap filling were 8.5%, 18.9%, and 32.9% (at 1, 3, and 6 months after surgery, respectively) in group L, while the progress levels at the same time points were 7.7%, 16.6%, and 24.4% in group C. There were significant differences at 6 months after surgery between the 2 groups. LIPUS accelerated bone healing at 6 months after OWHTO. It is important that the accuracy of LIPUS methods be further studied and improved.

Efficacy of extracorporeal shockwave therapy and low-intensity pulsed ultrasound in a rat knee osteoarthritis model: A randomized controlled trial.

This study aims to assess the efficacy of extracorporeal shockwave therapy (ESWT) and low-intensity pulsed ultrasound (LIPUS) on osteoarthritic rat knees. Twenty-four rats were divided into 3 groups: group 1-control (n=8), group 2-LIPUS (n=8) and group 3-ESWT (n=8). Cartilage degeneration was provided using mono-iodo-asetate (MIA). One milligram of MIA was delivered to the right knees in group 1 and both knees in group 2 and 3. A 0.09% saline solution was delivered to the left knees in group 1 for control. Twenty-four hours after the delivery, ESWT was applied once on the right knees in the group 2 rats to the medial tibia plateu with a 1 Hz frequency and 800 impulses. LIPUS was applied to the right knees in the group 2 rats to the medial tibia plateu with a 3 mHz frequency and 40 mW/cm2 intensity for 20 minutes over a period of 15 days. Pain scores were measured with a knee bend test. Bone mineral density measurements and scintigraphic bone scans were performed. Histopathological examination was done using a modified Mankin scale. There was no difference among the right knee subchondral bone osteoblastic activities (p>0.05). The left knee osteoblastic activities in the LIPUS and extracorporeal shockwave therapy (ESWT) groups were higher than those in the control group (p<0.05), but there was no difference between the LIPUS and ESWT groups. There was no difference among the groups for both knee subchondral bone BMD values (p>0.05). The modified Mankin scores of both the right and left knees of the ESWT and LIPUS groups were lower than those of the control group (p<0.05), but there was no difference between the ESWT and LIPUS groups. The pain scores of both knees of the ESWT and LIPUS groups at day 7 were higher than those of the control group (p<0.05), but there was no difference between the ESWT and LIPUS groups. There was no difference among the pain scores of the right knees at day 14 (p<0.05). ESWT and LIPUS have systemic proliferative and regenerative effects on cartilage and tissue.

Enhanced regeneration of large cortical bone defects with electrospun nanofibrous membranes and low-intensity pulsed ultrasound.

Poly-L-lactic acid (PLLA) nanofibrous membranes are widely utilized for tissue regeneration. Low intensity pulsed ultrasound (LIPUS) has been considered as a feasible modality for bone union. The aim of the present study was to investigate the potential synergistic effect of LIPUS and PLLA electrospun nanofibrous membranes on large cortical bone defects in rabbits in vivo. The bilateral rabbit tibia defect model was constructed using 18 adult NZ rabbits and the defect sites were treated with the nanofibrous membranes combined with LIPUS or nanofibrous membranes alone. A total of 3 to 6 weeks after surgery, bone defect healing was evaluated radiologically and histologically. Radiographs demonstrated that nascent bone formation in the central part of the defect regions was only observed in the nanofibrous membrane plus LIPUS group, whereas the bone defects were not fully healed in the group treated with nanofibrous membrane alone. Histology analysis of the LIPUS-treated group indicated that bone formation was thicker and more mature in the center of the defect site of the nanofibrous membrane plus LIPUS group. However, no differences were detected in the spatial and temporal pattern of the newly formed bone. Furthermore, the bone scores in the nanofibrous membrane plus LIPUS group were significantly greater than the scores exhibited in the nanofibrous membrane group at 3 and 6 weeks after surgery, respectively (P<0.01). In conclusion, the PLLA electrospun nanofibrous membrane combined with LIPUS indicated the capacity to improve the formation of nascent bone in rabbits with tibia defects. Further studies are required to fully elucidate the cell ingrowth depths inside nanofibrous membranes with scanning electron microscopy and the molecular effects of LIPUS on integrin and fibronectin.

Low-Intensity Pulsed Ultrasound Promotes Exercise-Induced Muscle Hypertrophy

The purpose of this study was to investigate whether low-intensity pulsed ultrasound (LIPUS) promotes exercise-induced muscle hypertrophy. Twenty-four adult Sprague-Dawley (SD) rats were randomly assigned to three groups (n = 8 per group): normal control group (NC), treadmill exercise group (TE) and treadmill exercise + LIPUS group (TE + LIPUS). The TE + LIPUS group received a LIPUS treatment (1 MHz, 30 mW/cm2) at the gastrocnemius for 20 min/d after treadmill exercise. The TE group was sham-treated. Eight weeks of treadmill training successfully established the exercise-induced muscle hypertrophy model. Muscle strength, muscle mass and muscle fiber cross-sectional area were significantly increased in the TE + LIPUS group compared with the TE group. Moreover, LIPUS treatment significantly upregulated the expression of Akt, mTOR, p-Akt and p-mTOR and significantly downregulated the expression of MSTN, ActRIIB, FoxO1 and its phosphorylation. The results indicated that LIPUS promotes exercise-induced muscle hypertrophy by facilitating protein synthesis and inhibiting the protein catabolism pathway.

Low-intensity pulsed ultrasound is effective for progressive-stage lumbar spondylolysis with MRI high-signal change.

This study aimed to investigate the treatment effects of low-intensity pulsed ultrasound (LIPUS) on progressive-stage spondylolysis. Spondylolysis is a stress fracture of the pars interarticularis. Based on the results of computed tomography, spondylolysis was classified into three categories: early, progressive, and terminal. Bone healing was prolonged or not obtained in progressive-stage spondylolysis. The progression of spondylolysis to nonunion has been associated with an increased incidence of spondylolisthesis. To prevent these clinical conditions, achieving bony healing of the spondylolysis site should be the goal of treatment. 15 consecutive pediatric patients with progressive-stage spondylolysis (defects) with MRI high-signal change were analyzed. Nine patients were treated conservative treatment including avoidance of any sport activity and the use of a brace during treatment (conventional). Six patients were treated using LIPUS everyday during treatment in addition to conservative treatment. Approximately every 1.5months, bone healing was evaluated via CT. Cases that retained defects after 4.5months were defined as nonunion. Two patients dropped out during the study period. A total of 13 patients (mean 14.6±2.5years) from the database met with 19 interarticularis defects. The bone union rate in LIPUS group was significantly higher than that in conventional group (66.7 vs. 10.0%, p=0.020). The treatment period to bone union was 3.8months and 2.7±0.3months in conventional and LIPUS groups. This study revealed that LIPUS treatment might be effective for bone union in patients with progressive-stage spondylolysis with MRI high-signal change. 4.

Abstract 13160: Low-intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Contractile Cardiac Function in Pressure-Overloaded Hearts in Mice

Introduction: Chronic pressure overload causes relative ischemia with resultant left ventricular (LV) dysfunction. Because the number of patients with chronic heart failure of ischemic origin is increasing worldwide, development of novel therapeutic strategies for those patients are needed. We have previously demonstrated that low-intensity pulsed ultrasound (LIPUS) improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. We also have recently reported that the LIPUS ameliorates post-MI LV remodeling in a mouse model of acute myocardial infarction (AMI). In the present study, we thus examined whether LIPUS also ameliorates contractile cardiac function in pressure-overloaded hearts in mice. Methods and Results: Chronic LV pressure overload was induced with transverse aortic constriction (TAC) in mice. The heart was treated with either placebo or LIPUS three times in the first week after TAC and was subsequently repeated once a week for 8 weeks. At 8 weeks, LV fractional shortening (LVFS) was significantly depressed in the placebo group, which was significantly ameliorated in the LIPUS group (36.2±3.8 vs. 30.4±0.5%, P&lt;0.05). Capillary density in the LV was significantly higher in the LIPUS group than in placebo group (4229±455 vs. 3243±143 /mm 2 , P&lt;0.05). Perivascular fibrosis was attenuated in the LIPUS group compared with the placebo group (P&lt;0.05). The mRNA expression of BNP and Collagen III (Iα) was lower in the LIPUS group than in the placebo group (both P&lt;0.05). Western blot analysis revealed that VEGF, eNOS and Hif-1α were significantly up-regulated in the LIPUS group (all P&lt;0.05 vs. placebo). Akt was also significantly activated in the LIPUS group (P&lt;0.05 vs. placebo). No adverse effect related to LIPUS therapy was noted. Conclusions: These results indicate that the LIPUS therapy ameliorates contractile cardiac function in pressure overload-induced cardiac dysfunction, for which enhanced myocardial angiogenesis may be involved. Thus, the LIPUS therapy may be a promising, non-invasive therapeutic strategy for the treatment of cardiac dysfunction due to pressure overload.

Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): randomized clinical trial

Objective To determine whether low intensity pulsed ultrasound (LIPUS), compared with sham treatment, accelerates functional recovery and radiographic healing in patients with operatively managed tibial fractures.Design A concealed, randomized, blinded,...