Acceleration of Bone-Tendon Interface Healing by Low-Intensity Pulsed Ultrasound Is Mediated by Macrophages

Abstract Objective Low-intensity pulsed ultrasound (LIPUS) has been proven to facilitate bone-tendon interface (BTI) healing and regulate some inflammatory cytokines. However, the role of macrophages, a key type of inflammatory cell, during treatment remains unknown. This study aimed to investigate the role of macrophages in the treatment of BTI injury with LIPUS in a rotator cuff tear animal model. Methods In this experimental and comparative study, a total of 160 C57BL/6 mature male mice that underwent supraspinatus tendon detachment and repair were randomly assigned to 4 groups: daily ultrasonic treatment and liposomal clodronate (LIPUS+LC), daily ultrasonic treatment and liposomes (LIPUS), daily mock sonication and liposomal clodronate (LC), and daily mock sonication and liposomes (control). LIPUS treatment was initiated immediately postoperatively and continued daily until the end of the experimental period. Results The failure load and stiffness of the supraspinatus tendon–humerus junction were significantly higher in the LIPUS group than in the other groups at postoperative weeks 2 and 4, whereas those in the LIPUS+LC and LC groups were lower than those in the control group at postoperative week 4. The LIPUS, LIPUS+LC, and LC groups exhibited significantly more fibrocartilage than the control group at 2 weeks. Only the LIPUS group had more fibrocartilage than the control group at 4 weeks. Micro–computed tomography results indicated that LIPUS treatment could improve the bone quality of the attachment site after both 2 and 4 weeks. When macrophages were depleted by LC, the bone quality–promoting effect of LIPUS treatment was significantly reduced. Conclusions The enhancement of BTI healing by LIPUS might be mediated by macrophages. Impact In our study, LIPUS treatment appeared to accelerate BTI healing, which was associated with macrophages based on our murine rotator cuff repair model. The expressions of macrophage under LIPUS treatment may offer a potential mechanism to explain BTI healing and the effects of LIPUS on BTI healing.

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Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Preconditioned by Low-Intensity Pulsed Ultrasound Stimulation Promote Bone-Tendon Interface Fibrocartilage Regeneration and Ameliorate Rotator Cuff Fatty Infiltration

10.21203/rs.3.rs-809653/v1 ◽

2021 ◽

Author(s):

Bing Wu ◽

Huabin Chen ◽

Xin Shi ◽

Lingfeng Wang ◽

Tao Zhang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Rotator Cuff ◽

Fatty Infiltration ◽

Supraspinatus Tendon ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Ultrasound Stimulation

Abstract Fibrovascular scar healing of bone-tendon interface (BTI) instead of functional fibrocartilage regeneration is the main concern associated with unsatisfactory prognosis in rotator cuff repair. Mesenchymal stem cells exosomes have been reported to be a new promising cell-free approach for rotator cuff healing. Whereas, controvercies abound in whether exosomes of native MSCs alone can effectively induce chondrogenesis. In this study, we aimed to explore the effect of Exosomes derived from low-intensity pulsed ultrasound stimulation (LIPUS)-preconditioned bone marrow mesenchymal stem cells (LIPUS-BMSC-Exos) or un-preconditioned BMSCs (BMSC-Exos) on rotator cuff healing and the underlying mechanism. Specifically, C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair were randomly assigned to saline, BMSCs-Exos or LIPUS-BMSC-Exos injection therapy. The results indicated that the biomechanical properties of the supraspinatus tendon-humeral junction were significantly improved in the LIPUS-BMSC-Exos group than that of the BMSCs-Exos group. The LIPUS-BMSC-Exos group also exhibited a higher histological score and more newly regenerated fibrocartilage at the repair site at postoperative 2 and 4 weeks and less fatty infiltration at 4 weeks than the BMSCs-Exos group. In vitro, co-culture of BMSCs with LIPUS-BMSC-Exos could significantly promote BMSCs chondrogenic differentiation and inhibit adipogenic differentiation than the BMSCs and BMSC-Exos co-cultured group did. Subsequently, quantitative real-time polymerase chain reaction revealed significantly higher enrichment of chondrogenic miRNAs and less enrichment of adipogenic miRNAs in LIPUS-BMSC-Exos compared with BMSC-Exos. Moreover, we demonstrated that this chondrogenesis-inducing potential was primarily attributed to miR-140, one of the most abundant miRNAs in LIPUS-BMSC-Exos. Collectively, our results highlight the regenerative potential of LIPUS-BMSC-Exos to promote BTI fibrocartilage regeneration and ameliorate supraspinatus fatty infiltration by positive regulation of pro-chondrogenetic and anti-adipogenetic of BMSCs differentiation which was primarily through delivering miR-140.

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Histological and Radiological Evaluation of Low-Intensity Pulsed Ultrasound Versus Whole Body Vibration on Healing of Mandibular Bone Defects in Rats

Medicina ◽

10.3390/medicina56090457 ◽

2020 ◽

Vol 56 (9) ◽

pp. 457

Author(s):

Milad Etemadi Sh ◽

Nan-Chen Hsieh ◽

Seyed Shahin Movahed Mohammadi ◽

Shahrooz Momeni ◽

Seyed Mohammad Razavi ◽

...

Keyword(s):

Bone Density ◽

Whole Body Vibration ◽

Bone Defects ◽

Whole Body ◽

Control Group ◽

Pulsed Ultrasound ◽

Mandibular Bone ◽

Body Vibration ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity

Background and Objectives: Mechanical stimulation can improve the structural properties of the fracture site and induce the differentiation of different cell types for bone regeneration. This study aimed to compare the effect of low-intensity pulsed ultrasound stimulation (LIPUS) versus whole body vibration (WBV) on healing of mandibular bone defects. Materials and Methods: A mandibular defect was created in 66 rats. The rats were randomly divided into two groups of rats. Each group was subdivided randomly by three groups (n = 11) as follows: (I) control group, (II) treatment with LIPUS, and (III) treatment with WBV. The radiographic changes in bone density, the ratio of lamellar bone to the entire bone volume, the ratio of the newly formed bone to the connective tissue and inflammation grade were evaluated after 1 and 2 months. Results: LIPUS significantly increased the radiographic bone density change compared to the control group at the first and second month postoperatively (p < 0.01). WBV only significantly increased the bone density compared to the control group at the second month after the surgery (p < 0.01). Conclusions: Application of LIPUS and WBV may enhance the regeneration of mandibular bone defects in rats. Although LIPUS and WBV are effective in mandibular bone healing, the effects of LIPUS are faster and greater than WBV.

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The Role of Low Intensity Pulsed Ultrasound Therapy in the Management of Acute Fractures: A Systematic Review

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0b013e318185e222 ◽

2008 ◽

Vol 65 (6) ◽

pp. 1446-1452 ◽

Cited By ~ 33

Author(s):

Xavier L. Griffin ◽

Isabel Costello ◽

Matthew L. Costa

Keyword(s):

Systematic Review ◽

Ultrasound Therapy ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity

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I–4 The Effect of Low-Intensity Pulsed Ultrasound (LIPUS) on Human Rotator Cuff Derived Cells

Journal of Orthopaedic Trauma ◽

10.1097/01.bot.0000450468.90398.57 ◽

2014 ◽

Vol 28 (6) ◽

pp. S3

Author(s):

Issei Nagura ◽

Takeshi Kokubu ◽

Takahiro Niikura ◽

Yutaka Mifune ◽

Atsuyuki Inui ◽

...

Keyword(s):

Rotator Cuff ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Human Rotator Cuff

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The effect of low-intensity pulsed ultrasound for tenogenesis of human rotator cuff cells

Journal of Shoulder and Elbow Surgery ◽

10.1016/j.jse.2014.01.024 ◽

2014 ◽

Vol 23 (5) ◽

pp. 601

Author(s):

Issei Nagura ◽

Takeshi Kokubu ◽

Yutaka Mifune ◽

Atsuyuki Inui ◽

Yoshifumi Harada ◽

...

Keyword(s):

Rotator Cuff ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Human Rotator Cuff

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Effects of low intensity pulsed ultrasound to reduce the effusion volumes and pain with knee osteoarthritis: a randomized controlled trial

International Journal of Research in Orthopaedics ◽

10.18203/issn.2455-4510.intjresorthop20185145 ◽

2018 ◽

Vol 5 (1) ◽

pp. 77

Author(s):

P. Shanmuga Raju ◽

Chokkarapu Ramu ◽

N. S. Harshavardhan ◽

K. Rajender ◽

G. Sachin

Keyword(s):

Randomized Controlled Trial ◽

Knee Osteoarthritis ◽

Controlled Trial ◽

Control Group ◽

Ultrasound Therapy ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Randomized Controlled ◽

And Control

Background: The study aim was to determine the effect of low intensity pulsed ultrasound therapy to reduce the effusion volumes and pain in patients with Knee OA.Methods: This study design was randomized controlled trial. Total 50 patients diagnosed with Knee osteoarthritis were randomly assigned to two groups. Group I was using treatment of low intensity pulsed ultrasound therapy and group II was administered TENS with home exercise respectively. Treatments were 6 days per week and duration of 2 week. The amount of effusion volume will be measured via ultrasonograpy in knee.Results: The maximum number of cases are lying in age group >60 years which is 28% and 40% in cases and control group respectively and age distribution in both the group is statistically not significant. The mean age of patients in cases and control group is 57.08±7.40 years and 58.04±9.93 years respectively.Conclusions: Low intensity pulsed ultrasound therapy significantly reduced the effusion volumes and pain in patients with knee osteoarthritis.

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Evaluation of histological changes in peri-implant bone tissue after ultrasound application at early healing stages

Stomatologist Minsk ◽

10.32993/stomatologist.2018.3(30).1 ◽

2018 ◽

pp. 38-42 ◽

Cited By ~ 1

Author(s):

S.P. Rubnikovich ◽

I.S. Khomich

Keyword(s):

Bone Tissue ◽

Dental Implants ◽

Morphological Changes ◽

Experimental Studies ◽

Low Frequency ◽

Control Group ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Dental Implantation

The aim was to study the nature of the morphological changes over time in the bone tissue around the implants under the influence of low-intensity pulsed ultrasound in the experiment. Materials and methods. Experimental studies were carried out on rabbits of the chinchilla breed, with dental implants installed in the tibia – two experimental groups with ultrasound and one control group. The animals were withdrawn from the experiment at 1, 2, 4 and 8 weeks and histological examination of the sections of peri-implant tissues was carried out. Results. The processes of osseointegration of dental implants in all groups of animals occurred without disrupting the normal process sequence. In the early stages granulation tissue is formed, later it is replaced by fibrous-reticular and coarse-fibrous bone tissue, and at the end – by a more mature lamellar bone tissue. However, the timing and degree of maturation of bone tissue, as well as osseointegration of implants in groups using low-frequency low-intensity pulsed ultrasound and without it differed significantly. The study showed that ultrasound exposure to implants and surrounding tissues induces osteoreparation processes, stimulating neoangiogenesis in granulation and newly formed bone tissue. Conclusion. Application of ultrasound to implants and subsequent application to the peri-implant tissues during and after dental implantation promotes the formation of bone tissue, identical by the histostructure to the maternal bone.

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A influência da irradiação ultrassônica de baixa intensidade em cultura de células fibroblásticas

Manual Therapy Posturology & Rehabilitation Journal ◽

10.17784/mtprehabjournal.2015.13.306 ◽

2015 ◽

Vol 13 ◽

pp. 306

Author(s):

Larissa Dragonetti Bertin ◽

Deise Aparecida Almeida Pires-Oliveira ◽

Priscila Daniela Oliveira ◽

Juliana Almeida Serpeloni ◽

Stheace Kelly Fernandes Szezerbaty ◽

...

Keyword(s):

Duty Cycle ◽

Healing Process ◽

Control Group ◽

Mitochondrial Activity ◽

Fibroblast Cells ◽

Pulse Regime ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity

Introduction: In vitro and in vivo put in evidence that the Low Intensity Pulsed Ultrasound therapy exerts a significant influence on cell function (cytoskeleton organization, stimulation of mitochondrial activity, ATP levels and plasma membrane). Objective: This study will analyze the radiation of low intensity pulsed ultrasound in fibroblast cells L 929. Method: In this study are presented the data from each exposure group average and standard deviation in each moment of evaluation (24 hours, 48 hours and 72 hours). The control group (received no radiation), 0.2 W/cm2 with 10% pulse regime (1: 9 duty cycle), 0.2 W / cm2 with 20% pulse regime (2: 8 cycle work), 0.4 W/cm2 with pulse scheme 10% (1: 9 duty cycle), 0.4 W/cm2 with pulse scheme 20% (2: 8 duty cycle). The analyzes will be performed through optical microscopy, MTT method 3 - (4,5-dimethylthiazol-2-yl) -2,5 diphenyl tetrazolium bromide, within the incubation times of 24, 48 and 72 hours. Results: Given the above study, the results presented in this project will be directed to increase the stimulation process and proliferation of fibroblast cells from the pulsed ultrasonic irradiation of low intensity, correlating with the healing process, neovascularization and repair. Conclusion: Therefore, the study of the effect of ultrasound from cell culture provides us with a simple and informative model on the significant aspects of the use of physical therapy in vivo system.

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Effect of Low Intensity Pulsed Ultrasound (LIPUS) on Tooth Movement and Root Resorption: A Prospective Multi-Center Randomized Controlled Trial

Journal of Clinical Medicine ◽

10.3390/jcm9030804 ◽

2020 ◽

Vol 9 (3) ◽

pp. 804 ◽

Cited By ~ 4

Author(s):

Tarek El-Bialy ◽

Khaled Farouk ◽

Terry D. Carlyle ◽

William Wiltshire ◽

Robert Drummond ◽

...

Keyword(s):

Tooth Movement ◽

Root Resorption ◽

Controlled Trial ◽

Control Group ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Control Side ◽

Before And After ◽

Group 1

The aim of this study was to evaluate the possible effect of low intensity pulsed ultrasound (LIPUS) on tooth movement and root resorption in orthodontic patients. Twenty-one patients were included in a split-mouth study design (group 1). Ten additional patients were included with no LIPUS device being used and this group was used as the negative control group (group 2). Group 1 patients were given LIPUS devices that were randomly assigned to right or left side on upper or lower arches. LIPUS was applied to the assigned side that was obtained by randomization, using transducers that produce ultrasound with a pulse frequency of 1.5 MHz, a pulse repetition rate of 1 kHz, and average output intensity of 30 mW/cm2. Cone-beam computed tomography (CBCT) images were taken before and after treatment. The extraction space dimensions were measured every four weeks and root lengths of canines were measured before and after treatment. The data were analyzed using paired t-test. The study outcome showed that the mean rate of tooth movement in LIPUS side was 0.266 ± 0.092 mm/week and on the control side was 0.232 ± 0.085 mm/week and the difference was statistically significant. LIPUS increased the rate of tooth movement by an average of 29%. For orthodontic root resorption, the LIPUS side (0.0092 ± 0.022 mm/week) showed a statistically significant decrease as compared to control side (0.0223 ± 0.022 mm/week). The LIPUS application accelerated tooth movement and minimized orthodontically induced tooth root resorption at the same time.

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