Ultrasound Therapy: Experiences and Perspectives for Regenerative Medicine

Abstract

Ultrasound has emerged as a novel tool for clinical applications, particularly in the context of regenerative medicine. Due to its unique physico-mechanical properties, low-intensity ultrasound (LIUS) has been approved for accelerated fracture healing and for the treatment of established non-union, but its utility has extended beyond tissue engineering to other fields, including cell regeneration. Cells and tissues respond to acoustic ultrasound by switching on genetic repair circuits, triggering a cascade of molecular signals that promote cell proliferation, adhesion, migration, differentiation, and extracellular matrix production. LIUS also induces angiogenesis and tissue regeneration and has anti-inflammatory and anti-degenerative effects. Accordingly, the potential application of ultrasound for tissue repair/regeneration has been tested in several studies as a stand-alone treatment and, more recently, as an adjunct to cell-based therapies. For example, ultrasound has been proposed to improve stem cell homing to target tissues due to its ability to create a transitional and local gradient of cytokines and chemokines. In this review, we provide an overview of the many applications of ultrasound in clinical medicine, with a focus on its value as an adjunct to cell-based interventions. Finally, we discuss the various preclinical and clinical studies that have investigated the potential of ultrasound for regenerative medicine.

Application of low-intensity pulsed therapeutic ultrasound on mesenchymal precursors does not affect their cell properties

“…Gross morphological analysis of stimulated s-MPs indicated that the protocol was not detrimental, as morphology was similar to control cells throughout the three-day application. However, it has also been described that LIPUS can induce apoptosis when higher intensities are applied [3,45,46] as occurs when we used 1 W/cm 2 intensity as a positive control for ultrasound stimulation. Therefore, LIPUS could be a potential tool for the treatment of some cancers [47].…”

“…Mechanical wave are sense by cell mechanoreceptors, that are transmembrane proteins that link with the cytoskeleton [2]. Once the mechanoreceptor receives the mechanical stimuli lead to the activation of different signaling pathways with finally rule cell fate, including quiescence, cell adhesion, proliferation, migration, differentiation, or apoptosis [3]. Hence, ultrasound, as mechanical stimuli, has the potential to regulate cell behavior.…”

Genetic response to low‑intensity ultrasound on mouse ST2 bone marrow stromal cells

“…Therapeutic LIUS has been used to enhance bone healing caused by fracture in humans ( 1 , 2 ). The effects and possible advantages of ultrasound have been a subject of increasing interest in other fields of medicine as well, including oncology, surgery, gene therapy and regenerative medicine ( 50 – 56 ). Therefore, genetic effects should also be considered to be a factor in these other fields.…”

Low-Intensity Continuous Ultrasound Therapies—A Systematic Review of Current State-of-the-Art and Future Perspectives

“…Soft tissue injuries can be divided into open wounds and deep tissue injuries (stress, strains, sprains, and tears). De Lucas et al reviewed the application of ultrasound therapy and the underlying activation of molecular and cellular pathways leading to cellular differentiation, proliferation, migration, matrix regeneration, and its biological effects in regenerative medicine [ 38 ]. The review extensively discussed LIPUS applications in clinical studies and respective regenerative outcomes in various tissues.…”

“…In contrast, LICUS stimulation has both mechanical and thermal effects at the tissue and cellular level. There are numerous comprehensive reviews that have described the effectiveness of LIPUS for various medical applications [ 24 , 38 , 39 , 40 , 41 ], but to our knowledge, there is no comprehensive review summarizing the therapeutic efficacy of LICUS. In the last few decades, there have been significant developments in LICUS applications.…”