Ultrasound as a stimulus for musculoskeletal disorders

Abstract

SummaryUltrasound is an inaudible form of acoustic sound wave at 20 kHz or above that is widely used in the medical field with applications including medical imaging and therapeutic stimulation. In therapeutic ultrasound, low-intensity pulsed ultrasound (LIPUS) is the most widely used and studied form that generally uses acoustic waves at an intensity of 30 mW/cm2, with 200 ms pulses and 1.5 MHz. In orthopaedic applications, it is used as a biophysical stimulus for musculoskeletal tissue repair to enhance tissue regeneration. LIPUS has been shown to enhance fracture healing by shortening the time to heal and reestablishment of mechanical properties through enhancing different phases of the healing process, including the inflammatory phase, callus formation, and callus remodelling phase. Reports from in vitro studies reveal insights in the mechanism through which acoustic stimulations activate cell surface integrins that, in turn, activate various mechanical transduction pathways including FAK (focal adhesion kinase), ERK (extracellular signal-regulated kinase), PI3K, and Akt. It is then followed by the production of cyclooxygenase 2 and prostaglandin E2 to stimulate further downstream angiogenic, osteogenic, and chondrogenic cytokines, explaining the different enhancements observed in animal and clinical studies. Furthermore, LIPUS has also been shown to have remarkable effects on mesenchymal stem cells (MSCs) in musculoskeletal injuries and tissue regeneration. The recruitment of MSCs to injury sites by LIPUS requires the SDF-1 (stromal cell derived factor-1)/CXCR-4 signalling axis. MSCs would then differentiate differently, and this is regulated by the presence of different cytokines, which determines their fates. Other musculoskeletal applications including bone–tendon junction healing, and distraction osteogenesis are also explored, and the results are promising. However, the use of LIPUS is controversial in treating osteoporosis, with negative findings in clinical settings, which may be attributable to the absence of an injury entry point for the acoustic signal to propagate, strong attenuation effect of cortical bone and the insufficient intensity for penetration, whereas in some animal studies it has proven effective.

3D Bone Biomimetic Scaffolds for Basic and Translational Studies with Mesenchymal Stem Cells

“…The produced scaffolds had different porosity (LH > (SH ~ LH) > SS), comparable wettability, and higher mechanical properties in the presence of higher porosity. MSC adhesion was higher on scaffolds with the SS pore geometry and low intensity pulsed ultrasound stimulation (LIPUS) further enhanced MSC proliferation, likely owing to mechanical stimulation of the adherent cells; in fact, LIPUS is already exploited in orthopedics as a biophysical stimulus to enhance musculoskeletal tissue repair [ 97 ].…”

Inhibitory effects of low intensity pulsed ultrasound on osteoclastogenesis induced in vitro by breast cancer cells

“…Ultrasound therapy can therefore be broadly divided into “low power” and “high power” applications, able to trigger a range of biological effects in relation to the exposure levels employed; although there is still no widely accepted definition of low-intensity ultrasound [ 44 ] the “low power” group includes physiotherapy and fracture repair (generally 30 mW/cm 2 , with 200 ms pulses and 1.5 MHz) [ 45 ], sonophoresis, sonoporation and gene therapy (usually 1.0–2.0 MHz at an intensity of 0.5 to 3.0 W/cm 2 ) [ 44 ], whereas the most common use of “high power” ultrasound in medicine is high-intensity focused ultrasound (HIFU) (employed generally at an intensity≥3 W/cm 2 and a frequency of 1–20 MHz) [ 27 ]. While useful therapeutic effects are now being demonstrated clinically, the mechanisms by which they happen are often not well understood [ 27 ].…”

Synergies of accelerating differentiation of bone marrow mesenchymal stem cells induced by low intensity pulsed ultrasound, osteogenic and endothelial inductive agent

“…LIPUS may be a new and effective method. LIPUS is used to promote bone healing, which mechanisms perhaps by promoting different processes from several aspects during each phase of the healing process [18]. One most important mechanism is LIPUS can promote the differentiation of stem cells into osteoblasts [19][20][21] through increases in alkaline phosphatase (ALP), osterix (OSX), receptor activator of nuclear factor-kappa B ligand (RANKL), and runt-related transcription factor 2 (RUNX2), and decreases in osteoprotegerin (OPG) [22].…”