Stimulation of Bone Repair with Ultrasound

Abstract

This chapter reviews the different options available for the use of ultrasound in the enhancement of fracture healing or in the reactivation of a failed healing process: LIPUS, shock waves and ultrasound-mediated delivery of bioactive molecules, such as growth factors or plasmids. The main emphasis is on LIPUS, or Low Intensity Pulsed Ultrasound, the most widespread and studied technique. LIPUS has pronounced bioeffects on tissue regeneration, while employing intensities within a diagnostic range. The biological response to LIPUS is complex as the response of numerous cell types to this stimulus involves several pathways. Known to-date mechanotransduction pathways involved in cell responses include MAPK and other kinases signaling pathways, gap-junctional intercellular communication, up-regulation and clustering of integrins, involvement of the COX-2/PGE2 and iNOS/NO pathways, and activation of the ATI mechanoreceptor. Mechanisms at the origin of LIPUS biological effects remain intriguing, and analysis is hampered by the diversity of experimental systems used in-vitro. Data point to clear evidence that bioeffects can be modulated by direct and indirect mechanical effects, like acoustic radiation force, acoustic streaming, propagation of surface waves, heat, fluid-flow induced circulation and redistribution of nutrients, oxygen and signaling molecules. One of the future engineering challenge is therefore the design of dedicated experimental set-ups allowing control of these different mechanical phenomena, and to relate them to biological responses. Then, the derivation of an 'acoustic dose' and the cross-calibration of the different experimental systems will be possible. Despite this imperfect knowledge of LIPUS biophysics, the clinical evidence, although most often of low quality, speaks in favor of the clinical use of LIPUS, when the economics of nonunion and the absence of toxicity of this ultrasound technology are taken into account.

Bone marrow mesenchymal stem cells stimulated with low‐intensity pulsed ultrasound: Better choice of transplantation treatment for spinal cord injury

“…LIPUS is a noninvasive and safe form of mechanical energy that can be delivered into biological tissues and cells as acoustic pressure waves, which has been widely used for clinical applications including bone fracture healing, rehabilitation treatment of tendon, ligament, and cartilage disorders . Furthermore, LIPUS stimulation has been certified and approved by Food and Drug Administration (FDA) in the United States as a safe and effective treatment strategy .…”

“…LIPUS is a noninvasive and safe form of mechanical energy that can be delivered into biological tissues and cells as acoustic pressure waves, 32 which has been widely used for clinical applications including bone fracture healing, rehabilitation treatment of tendon, ligament, and cartilage disorders. [33][34][35][36][37][38] BMSCs transplantation has proven to be an effective treatment strategy for SCI. 48 κB receptor, preventing the activation of NF-κB signaling pathway.…”

Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation

“…Numerous studies have shown that mechanical stimulation of bone progenitors including ultrasound [23], mechanical strain [24, 25], and compression as well as shear forces has a stimulatory effect on bone progenitors involved in bone healing of critical size defects and nonunions in vivo. A broad set of investigations has aimed to unravel potential underlying molecular mechanisms and growth factor pathways involved with sophisticated in vitro methods [26].…”

The application of low-frequency ultrasound for the comprehensive treatment and rehabilitation of the patients presenting with chronic endometritis

“…Некротический слой фрагментируется и отслаивается, в очаг легко проникают фагоцитирующие нейтрофилы. Однако регенерация тканей ускоряется не только вследствие интенсивного очищения раны, но и благодаря тому, что ультразвук стимулирует синтез коллагена [7][8][9], созревание соединительной ткани и способствует формированию более эластичного рубца. Под действием низкочастотного ультразвука происходит активация синтеза протеинов фибробластами и факторов роста макрофагами.…”