Application of Ultrasound Stimulation in Bone Tissue Engineering

Abstract

Many studies have been investigated on the effects of the low-intensity pulsed ultrasound (LIPUS) on bone healing, acceleration of bone mineralization and regeneration. Many researchers have focused on a more comprehensive understanding of the biological mechanism of the osteoblast by LIPUS because the osteoblast is an important cell in bone formation. The effects of LIPUS on the proliferation, gene expression of Runx2, Msx2, Dlx5, and AJ18, and the second messenger signaling of osteoblast were reported. Various parameters of LIPUS, such as intensity, frequency, duration and topology, were investigated to find appropriate conditions in osteoblast. Less than 120 mW/cm 2 of intensity and 1-3 MHz of frequency were considered good condition for regeneration of bone tissue. Increased osteoblast cells and higher mineralized nodule formation explain the enhancement of proliferation by LIPUS. In addition, LIPUS affects on differentiation of osteoblast cells, which is shown by increased ALPase, and transcriptional factors, Runx2. Ultrasound stimulates PEG2 and COX-2 in osteoblast, and the signals accelerates the bone regeneration in tissue engineering.

Low Intensity Pulsed Ultrasound for Accelerating Distraction Osteogenesis: A Systematic Review of Experimental Animal Studies

“…Using this intensity, the authors also reported increased bone regeneration in comparison to the control group. These results are in accordance with other reports regarding bone fracture repair, which indicate that the appropriate intensity is generally < 100 mW/cm 2 and usually in the range of 20-50 mW/cm 2 [30].…”

Changing Paradigms in Cranio-Facial Regeneration: Current and New Strategies for the Activation of Endogenous Stem Cells

“…Ultrasounds are mechanical waves (sound waves) characterized by frequencies higher than the upper audible limit of the human hearing. The use of ultrasounds skyrocketed in the last decades both in diagnostics and in therapy; as for bone healing, the most used ultrasound-based technique is LIPUS (Low-Intensity Pulsed Ultrasound Stimulation), which has been tested with various successes in case of bone fractures and non-unions (Watanabe et al, 2010 ; Yang et al, 2010 ). The biology of ultrasound effects on bone tissue has been a mystery until very recently, although the role of mechanical stresses is well-known in the scientific community since a long time (Carter, 1987 ); therefore, today is universally accepted that mechanical forces are a major determinant of stem cells self-renewal and fate decision, as their roles have been assessed in embryonic and mesenchymal stem cells (Li D. et al, 2011 ).…”

Multimodal Imaging and Theranostic Application of Disease-Directed Agents

“…Lastly, US stimulation positively influences bone tissue through biological mechanisms including cellular adhesion, proliferation, differentiation, and gene expression. Although clinical studies, such as an experiment which demonstrated a 38% decrease in the overall healing time of cortical fractures, have been conducted that validate US stimulation applications in bone tissue engineering, more research is required to develop clinical strategies [63].…”