Incorporation of synthetic water-soluble curcumin polymeric drug within calcium phosphate cements for bone defect repairing.
Incorporation of synthetic water-soluble curcumin polymeric drug within calcium phosphate cements for bone defect repairing.
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DOI：
10.1016/j.mtbio.2023.100630
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发表时间：
2023-06
影响因子：
8.2
通讯作者：
Hao, Dingjun
中科院分区：
文献类型：
--
作者：
Zhang, Ying;Xu, Hailiang;Wang, Jing;Fan, Xiaochen;Tian, Fang;Wang, Zhiyuan;Lu, Botao;Wu, Weidong;Liu, Youjun;Ai, Yixiang;Wang, Xiaohui;Zhu, Lei;Jia, Shuaijun;Hao, Dingjun
自固化磷酸钙骨水泥（CPC）的骨再生能力有限，降解性差，需要对其大孔结构进行修饰，并添加活性成骨物质。姜黄素（Curcumin，CUR）是一种水溶性高分子，具有很强的成骨活性，但水溶性和生物利用度较差。本研究将CUR-HA和葡萄糖微粒（glucose microparticles，GMP）掺入CPC粉末中，制备了CUR-HA/GMP/CPC复合材料，该复合材料不仅保留了骨水泥良好的可注射性和机械强度，而且显著提高了骨水泥的孔隙率和体外缓释性能。CUR-HA掺入通过激活RUNX家族转录因子2/成纤维细胞生长因子18（RUNX 2/FGF 18）信号通路、增加骨钙素表达和增强碱性磷酸酶活性，大大提高骨髓间充质干细胞（BMSC）向成骨细胞分化的能力。此外，CUR-HA/GMP/CPC植入股骨髁骨缺损后，骨水泥降解速度明显加快，局部血管化程度增加，骨桥蛋白表达增强，骨组织再生速度加快。因此，大孔CPC复合CUR-HA骨水泥具有良好的骨缺损修复能力，是改性CPC在临床上的一种很有前景的转化应用。透明质酸对姜黄素进行修饰，大大提高了姜黄素的水溶性，并保持了姜黄素的生物活性。加入改性姜黄素（CUR-HA）对磷酸钙骨水泥（CPC）的可注射性和力学参数无明显影响。CUR-HA/GMP（葡萄糖微粒）/CPC复合物通过RUNX 2/FGF 18信号通路促进BMSCs向成骨细胞分化。CUR-HA的加入加速了CPC的降解，促进了新骨的形成。
Modified macroporous structures and active osteogenic substances are necessary to overcome the limited bone regeneration capacity and low degradability of self-curing calcium phosphate cement (CPC). Curcumin (CUR), which possesses strong osteogenic activity and poor aqueous solubility/bioavailability, esterifies the side chains in hyaluronic acid (HA) to form a water-soluble CUR-HA macromolecule. In this study, we incorporated the CUR-HA and glucose microparticles (GMPs) into the CPC powder to fabricate the CUR-HA/GMP/CPC composite, which not only retained the good injectability and mechanical strength of bone cements, but also significantly increased the cement porosity and sustained release property of CUR-HA in vitro. CUR-HA incorporation greatly improved the differentiation ability of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts by activating the RUNX family transcription factor 2/fibroblast growth factor 18 (RUNX2/FGF18) signaling pathway, increasing the expression of osteocalcin and enhancing the alkaline phosphatase activity. In addition, in vivo implantation of CUR-HA/GMP/CPC into femoral condyle defects dramatically accelerated the degradation rate of cement and boosted local vascularization and osteopontin protein expression, and consequently promoted rapid bone regeneration. Therefore, macroporous CPC based composite cement with CUR-HA shows a remarkable ability to repair bone defects and is a promising translational application of modified CPC in clinical practice. Modification of curcumin by hyaluronic acid greatly increases its water solubility and preserves the biological activity of curcumin. The addition of modified curcumin (CUR-HA) did not significantly affect the injectability and mechanical parameters of calcium phosphate cement (CPC). The CUR-HA/GMP (glucose microparticle)/CPC composite promotes the differentiation of BMSCs into osteoblasts through the RUNX2/FGF18 signaling pathway. The incorporation of CUR-HA accelerated the degradation of CPC and promoted new bone formation.
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DOI：
10.1002/advs.202004793
发表时间：
2021-05
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Chen Z;Zhang F;Zhang H;Cheng L;Chen K;Shen J;Qi J;Deng L;He C;Santos HA;Cui W
通讯作者：
Cui W
影响因子：
4.3
作者：
Khezri K;Maleki Dizaj S;Rahbar Saadat Y;Sharifi S;Shahi S;Ahmadian E;Eftekhari A;Dalir Abdolahinia E;Lotfipour F
通讯作者：
Lotfipour F
古老药物姜黄素通过直接抑制双特异性酪氨酸调节激酶2来阻碍26S蛋白酶体活性
DOI：
10.1073/pnas.1806797115
发表时间：
2018-08-07
影响因子：
11.1
作者：
Banerjee S;Ji C;Mayfield JE;Goel A;Xiao J;Dixon JE;Guo X
通讯作者：
Guo X
影响因子：
15.1
作者：
Bao, Ziting;Gu, Zhipeng;Wu, Jun
通讯作者：
Wu, Jun
影响因子：
168.9
作者：
Balogh, Zsolt J.;Reumann, Marie K.;Bhandari, Mohit
通讯作者：
Bhandari, Mohit