Low-Intensity Pulsed Ultrasound Augments Tendon, Ligament, and Bone–Soft Tissue Healing in Preclinical Animal Models: A Systematic Review

Lai, Wilson C; Iglesias, Brenda; Mark, Bryan J.; Wang, Dean

doi:10.1016/j.arthro.2021.02.019

Cited by 33 publications

(29 citation statements)

References 59 publications

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“…The final class of animal investigations they reviewed focused on soft tissue to bone healing (11 studies evaluating patellar tendon repair; 2 studies on anterior cruciate ligament reconstruction; 1 study looking at rotator cuff repair; 1 study evaluating extensor digitorum longus transfer) in either rabbits (13 studies) or sheep (2 studies, including the one assessing rotator cuff repair). 1 Positive results found with LIPUS in the majority of these animal investigations starkly contrast with the lack of benefit seen in either human trial: a 48-subject study of elbow lateral epicondylitis and a 37-subject investigation of patellar tendonitis. 2,3 Both trials used sham ultrasound devices in their placebo arm.…”

Section: Houston Texasmentioning

confidence: 98%

“…Such issues are revealed in the systematic review by Lai, Iglesias, Mark, and Wang, "Low-Intensity Pulsed Ultrasound Augments Tendon, Ligament, and Bone-Soft Tissue Healing in Preclinical Animal Models." 1 Those authors found ample evidence among 28 animal studies that low-intensity pulsed ultrasonography (LIPUS) improves mechanical properties, microscopic appearance, and even biochemical markers of healing response after injury/repair of tendons, ligaments, and soft tissue to bone junctions. And yet no benefit of LIPUS was seen in the 2 randomized,…”

Section: See Related Article On Page XXXmentioning

confidence: 99%

“…Ó placebo-controlled human trials they also reviewed after searching for English-languageepublished investigations on this treatment modality. Animal studies reviewed by Lai et al 1 included 9 investigations of healing after surgical tenotomy/ tendon repair (6 studies evaluating Achilles tendons; 2 evaluating patellar tendons; 1 evaluating profundus tendon) in just 2 animal models (7 studies on rats; 2 on rabbits). They also reviewed 4 studies of ligament healingdall assessing medial collateral ligament transection (3 studies in rats; 1 in rabbits).…”

Section: Houston Texasmentioning

confidence: 99%

“…Perhaps the number of subjects involved in these clinical trials was insufficient to detect the benefit of LIPUS. However, as Lai et al 1 themselves point out, every one of the animal models was investigating healing of an acute soft tissue insult, whereas the human trials were evaluating chronic conditions. So maybe LIPUS is less useful for such chronic conditions typically associated with repetitive overuse injury.…”

Section: Houston Texasmentioning

confidence: 99%

“…Yet the difference in the size of mammalian cells responsible for repair of these structures is not so similarly immense, which may have a profound impact, in and of itself, on the capacity for effective repair. But only 2 of the 28 animal studies investigating LIPUS found in the literature search by Lai et al 1 used animals of a size within even an order of magnitude of humans; they list no investigations using this modality on dogs, goats, or primates.…”

Section: Houston Texasmentioning

confidence: 99%

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Ilahi¹

2021

Arthroscopy: The Journal of Arthroscopic & Related Surgery

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Efficacy of low-intensity pulsed ultrasonography (LIPUS) has been demonstrated in several mammalian models of injury/repair of tendons, ligaments, and soft tissue-bone junctions. But human studies have not demonstrated benefit from such intervention. In addition to innate healing differences between humans and research animals, another reason for this outcome variance may be that animal investigations of LIPUS have so far focused on healing after acute intervention, whereas randomized clinical trials have only looked at treating chronic tendinopathy in symptomatic patients. On the basis of current animal data, potential clinical benefit of LIPUS is most likely to be demonstrated for addressing acute injuries or postoperative scenarios. Yet, a particularly important anatomic difference between humans and experimental land animals regarding ultrasonography is the presence of subcutaneous adipose in the former versus the lack thereof in the latter, especially in the extremities, because overlying adipose attenuates ultrasound waves directed at underlying injured, repaired, or reconstructed tissues.

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Section: Houston Texasmentioning

confidence: 98%

Section: See Related Article On Page XXXmentioning

confidence: 99%

Section: Houston Texasmentioning

confidence: 99%

Section: Houston Texasmentioning

confidence: 99%

Section: Houston Texasmentioning

confidence: 99%

See 3 more Smart Citations

Editorial Commentary: Treatment Efficacy Found in Animal Studies May Not Translate to Humans

Ilahi¹

2021

Arthroscopy: The Journal of Arthroscopic & Related Surgery

View full text Add to dashboard Cite

show abstract

Ultrasound and shockwave therapy for acute fractures in adults

Searle

Lewis

Coyle

et al. 2023

Cochrane Database of Systematic Reviews

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Low‐intensity pulsed ultrasound alleviates doxorubicin‐induced cardiotoxicity via inhibition of S100a8/a9‐mediated cardiac recruitment of neutrophils

Zhu

Wang

et al. 2023

Bioengineering & Transla Med

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Doxorubicin (DOX)‐induced cardiotoxicity limits its broad use as a chemotherapy agent. The development of effective and non‐invasive strategies to prevent DOX‐associated adverse cardiac events is urgently needed. We aimed to examine whether and how low‐intensity pulsed ultrasound (LIPUS) plays a protective role in DOX‐induced cardiotoxicity. Male C57BL/6J mice were used to establish models of both acute and chronic DOX‐induced cardiomyopathy. Non‐invasive LIPUS therapy was conducted for four consecutive days after DOX administration. Cardiac contractile function was evaluated by echocardiography. Myocardial apoptosis, oxidative stress, and fibrosis were analyzed using terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling (TUNEL) staining, dihydroethidium (DHE) staining, and picrosirius red staining assays. RNA‐seq analysis was performed to unbiasedly explore the possible downstream regulatory mechanisms. Neutrophil recruitment and infiltration in the heart were analyzed by flow cytometry. The S100a8/a9 inhibitor ABR‐238901 was utilized to identify the effect of S100a8/a9 signaling. We found that LIPUS therapy elicited a great benefit on DOX‐induced heart contractile dysfunction in both acute and chronic DOX models. Chronic DOX administration increased serum creatine kinase and lactate dehydrogenase levels, as well as myocardial apoptosis, all of which were significantly mitigated by LIPUS. In addition, LIPUS treatment prevented chronic DOX‐induced cardiac oxidative stress and fibrosis. RNA‐seq analysis revealed that LIPUS treatment partially reversed alterations of gene expression induced by DOX. Gene ontology (GO) analysis of the downregulated genes between DOX‐LIPUS and DOX‐Sham groups indicated that inhibition of neutrophil chemotaxis might be involved in the protective effects of LIPUS therapy. Flow cytometry analysis illustrated the inhibitory effects of LIPUS on DOX‐induced neutrophil recruitment and infiltration in the heart. Moreover, S100 calcium binding protein A8/A9 (S100a8/a9) was identified as a potential key target of LIPUS therapy. S100a8/a9 inhibition by ABR‐238901 showed a similar heart protective effect against DOX‐induced cardiomyopathy to LIPUS treatment. LIPUS therapy prevents DOX‐induced cardiotoxicity through inhibition of S100a8/a9‐mediated neutrophil recruitment to the heart, suggesting its potential application in cancer patients undergoing chemotherapy with DOX.

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Low-Intensity Pulsed Ultrasound Augments Tendon, Ligament, and Bone–Soft Tissue Healing in Preclinical Animal Models: A Systematic Review

Cited by 33 publications

References 59 publications

Editorial Commentary: Treatment Efficacy Found in Animal Studies May Not Translate to Humans

Editorial Commentary: Treatment Efficacy Found in Animal Studies May Not Translate to Humans

Ultrasound and shockwave therapy for acute fractures in adults

Low‐intensity pulsed ultrasound alleviates doxorubicin‐induced cardiotoxicity via inhibition of S100a8/a9‐mediated cardiac recruitment of neutrophils

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