Study on the angiogenesis-mediated promotion of bone fracture healing using repeated stimuli induced by microbubble destruction

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Bone fracture may trigger elderly people to have osteoporosis, become bedridden, or require nursing care, and furthermore, disturb the bone growth of growing children and increase osteoporosis reserves in the future. To evade these issues, it is required to hasten bone fracture healing and prevent bone atrophy due to the long-term rest, allowing early postoperative ambulation and rehabilitation. Thus, this study was undertaken to clarify the effect of angiogenesis, which promoted by microbubble destruction, on bone fracture healing.In the 1st year, we performed the pilot study based on μCT to observe the process of bone regeneration and angiogenesis within the bone deficit in rat cortical bone. Woven bone and angiogenesis appeared one week later the deficit operation and its adjacent medullary region. Another week later, the woven bone in the medullary region disappeared with blood vessels, while the woven bone in the cortical bone region remained with sparsely-distributed blood vessel … More s. That is, angiogenesis participated only in the early period of bone healing process. In the 2nd year, we established an in vivo μCT technique to measure bone healing process in the mouse tibia and developed the software to analyze the temporal changes of bone morphometry. On the basis of the in vivo μCT measurement, we could confirm the generation of woven bone and the replacement of it with new bone from the circumference toward the center. As for the last year, to examine the effect of microbubble circulation on bone fracture healing, we performed a μCT measurement of rat tibial bone deficit under microbubble perfusion. No effect of microbubble was found on bone fracture healing. Subsequently we developed an ultrasonic wave generation system. Then, considering a half-time period of spontaneous decay of bubbles and a circulatory time for bubbles to reach the bone deficit region after administration, we examined the timing and the duration to load sound pressure. Presently, we are evaluating the promotive effect of microbubble destruction on angiogenesis and bone regeneration. Less