Jiwoon Jeong1,2, Jung Hee Shim3,4, Bum Mo Koo2, Young Bin Choy1,5,6, Chan Yeong Heo7,8,9. 1. Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, Republic of Korea. 2. R&D Center, OSFIRM Co., Ltd., Seongnam-si, Gyeonggi-do, Republic of Korea. 3. Department of Research Administration Team, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea. 4. Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea. 5. Department of Biomedical Engineering, College of Medicine, Seoul National University, Seoul, Republic of Korea. 6. Medical Research Center, Institution of Medical & Biological Engineering, Seoul National University, Seoul, Republic of Korea. 7. Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, Republic of Korea. lionheo@gmail.com. 8. Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea. lionheo@gmail.com. 9. Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul, Republic of Korea. lionheo@gmail.com.
Abstract
BACKGROUND: Due to the increasing aging of society, the number of patients suffering from senile diseases is increasing. Patients suffering from osteoporosis, which is a representative senile disease, take a long time to recover from fractures, and the resulting mortality rate is very high. Alendronate (Ald), which is widely used as a treatment for osteoporosis, alleviates osteoporosis by inhibiting osteoclasts. In addition, whitlockite (WH) promotes the osteogenic differentiation of bone cells and improves bone regeneration. Therefore, we intended to bring about a synergistic effect by using these substances together. METHODS: In this study, a scaffold composed of gelatin/heparin was fabricated and applied to effectively use WH and Ald together. A scaffold was constructed using gelatin and heparin was used to effectively utilize the cations released from WH. In addition, it formed a porous structure for effective bone regeneration. In vitro and in vivo osteoclast inhibition, osteogenic differentiation, and bone regeneration were studied using the prepared scaffolds. RESULTS: The inhibition of osteoclast was much higher when WH and Ald were applied in combination rather than individually. The highest level of osteogenic differentiation was observed when both substances were applied simultaneously. In addition, when applied to bone regeneration through the mouse calvarial defect model, combined treatment showed excellent bone regeneration. CONCLUSION: Therefore, this study showed the synergistic effect of WH and Ald, and it is suggested that better bone regeneration is possible by applying this treatment to bones with fractures that are difficult to regenerate.
BACKGROUND: Due to the increasing aging of society, the number of patients suffering from senile diseases is increasing. Patients suffering from osteoporosis, which is a representative senile disease, take a long time to recover from fractures, and the resulting mortality rate is very high. Alendronate (Ald), which is widely used as a treatment for osteoporosis, alleviates osteoporosis by inhibiting osteoclasts. In addition, whitlockite (WH) promotes the osteogenic differentiation of bone cells and improves bone regeneration. Therefore, we intended to bring about a synergistic effect by using these substances together. METHODS: In this study, a scaffold composed of gelatin/heparin was fabricated and applied to effectively use WH and Ald together. A scaffold was constructed using gelatin and heparin was used to effectively utilize the cations released from WH. In addition, it formed a porous structure for effective bone regeneration. In vitro and in vivo osteoclast inhibition, osteogenic differentiation, and bone regeneration were studied using the prepared scaffolds. RESULTS: The inhibition of osteoclast was much higher when WH and Ald were applied in combination rather than individually. The highest level of osteogenic differentiation was observed when both substances were applied simultaneously. In addition, when applied to bone regeneration through the mouse calvarial defect model, combined treatment showed excellent bone regeneration. CONCLUSION: Therefore, this study showed the synergistic effect of WH and Ald, and it is suggested that better bone regeneration is possible by applying this treatment to bones with fractures that are difficult to regenerate.
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