Interdisciplinary Program in Bioengineering, Seoul National University, Seoul, Republic of Korea.
R&D Center, OSFIRM Co., Ltd., Seongnam-si, Gyeonggi-do, Republic of Korea.
Tissue Eng Regen Med. 2022 Feb;19(1):83-92. doi: 10.1007/s13770-021-00416-2. Epub 2021 Dec 28.
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.
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.
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.
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.
由于社会老龄化的加剧,患有老年病的患者人数正在增加。患有骨质疏松症(一种代表性的老年疾病)的患者骨折后需要很长时间才能康复,由此导致的死亡率非常高。阿仑膦酸钠(Ald)作为治疗骨质疏松症的常用药物,通过抑制破骨细胞来缓解骨质疏松症。此外,磷灰石(WH)促进成骨细胞的成骨分化,从而改善骨再生。因此,我们旨在通过联合使用这些物质来产生协同作用。
在这项研究中,制备了由明胶/肝素组成的支架,并将其用于有效地共同使用 WH 和 Ald。使用明胶和肝素构建支架,以有效地利用 WH 释放的阳离子。此外,它形成了一个多孔结构,有利于有效的骨再生。使用所制备的支架研究了体外和体内破骨细胞抑制、成骨分化和骨再生。
WH 和 Ald 联合应用时的破骨细胞抑制作用明显高于单独应用时。当两种物质同时应用时,观察到最高水平的成骨分化。此外,当通过小鼠颅骨缺损模型应用于骨再生时,联合治疗显示出优异的骨再生。
因此,本研究表明了 WH 和 Ald 的协同作用,通过将这种治疗方法应用于难以再生的骨折骨骼,可能会实现更好的骨再生。