Microbubble-Mediated Ultrasound Outweighs Low-Intensity Pulsed Ultrasound on Osteogenesis and Neovascularization in a Rabbit Model of Steroid-Associated Osteonecrosis

Abstract

Microbubbles magnify the acoustic pressure of low-intensity pulsed ultrasound (LIPUS) and may enhance its bioeffect for diagnostic and therapeutic purposes. This study compared the effect of this novel microbubble-mediated ultrasound (MUS) with that of the traditional LIPUS on osteogenesis and neovascularization in a rabbit model of steroid-associated osteonecrosis. We hypothesized that MUS might outweigh LIPUS on promoting osteogenesis and neovascularization in steroid-associated osteonecrosis. The bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in the rabbits. The indices of bone mineral density (BMD), trabecular number, maximal loading strength, and mineral apposition rate were analyzed, demonstrating that the animal model of steroid-associated osteonecrosis was successfully established. Both the MUS group (GM) and the LIPUS group (GL) were insonated 20 min daily for six weeks. GM received an extra intracapsular injection of microbubbles before insonation every other day. Fluorescence bone labeling, Micro-CT Analysis, biomechanical test, quantitative real-time PCR, Western blot analysis, and histological evaluation were performed for comparing GM with GL. The results demonstrated a 39% higher mineral apposition rate in GM compared with GL. The BMD and the maximal loading strength of femoral head of GM increased by 4.3% and 27.8% compared to those of GL, respectively. The mRNA and protein expression of BMP-2 and VEGF were also significantly higher in GM. The number of blood vessels of GM was 65% greater than that of GL. MUS is more potent than LIPUS in enhancing osteogenesis, neovascularization, and biomechanical strength of femoral head in the animal model of steroid-associated osteonecrosis. Without increasing the intensity of insonation or the risk of tissue damage, MUS is better for inhibiting the process of steroid-associated osteonecrosis.

Mechanically superior matrices promote osteointegration and regeneration of anterior cruciate ligament tissue in rabbits

“…7E). Several other studies have demonstrated that the application of compressive forces on bone enhances the mineral apposition rate (57,58). Furthermore, our reported mineral apposition rates are in agreement with other studies conducted in rabbit models (57).…”

Low-intensity pulsed ultrasound/nanomechanical force generators enhance osteogenesis of BMSCs through microfilaments and TRPM7

“…Gas filled microbubbles can amplify the sound pressure and enhance the biological effects of ultrasound, improving the therapeutic effect of LIPUS [21][22][23]. The ultrasonic pulse produces volume pulsation of the microbubbles and generate fluid microflow around the microbubbles, resulting in local shear force on the cells [24].…”

Low‐intensity pulsed ultrasound induces proliferation of human neural stem cells

“…Regarding possible clinical translation of the present research, LIPUS may be effective as a sole therapeutic tool or combined with another therapeutic approach such as microbubbles, which has been reported to enhance the LIPUS effects on cell proliferation and differentiation [75][76][77] and neovascularisation, 78 for stem cell therapy and tis-sue engineering approaches in the regenerative medicine. More specifically related to the present study, the LIPUSinduced cell proliferation of neural stem cells would benefit nerve repair and regeneration approaches like induction of nerve supply for regenerative endodontic treatment and management of traumatic nerve injuries.…”