Hyaluronic acid facilitates bone repair effects of calcium phosphate cement by accelerating osteogenic expression

透明质酸通过加速成骨表达促进磷酸钙水泥的骨修复作用

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作者:Xu Cui, Chengcheng Huang, Zhizhen Chen, Meng Zhang, Chunyu Liu, Kun Su, Jianyun Wang, Li Li, Renxian Wang, Bing Li, Dafu Chen, Changshun Ruan, Deping Wang, William W Lu, Haobo Pan

Abstract

Calcium phosphate cements (CPC) are widely anticipated to be an optimum bone repair substitute due to its satisfied biocompatibility and degradability, suitable to be used in minimally invasive treatment of bone defects. However the clinical application of CPC is still not satisfied by its poor cohesiveness and mechanical properties, in particular its osteoinductivity. Hyaluronic acid reinforced calcium phosphate cements (HA/CPC) showed extroadinary potential not only enhancing the compressive strength of the cements but also significantly increasing its osteoinductivity. In our study, the compressive strength of HA/CPC increased significantly when the cement was added 1% hyaluronic acid (denoted as 1-HA/CPC). In the meantime, hyaluronic acid obviously promoted ALP activity, osteogenic related protein and mRNA expression of hBMSCs (human bone marrow mesenchymal stem cells) in vitro, cement group of HA/CPC with 4% hyaluronic acid adding (denoted as 4-HA/CPC) showed optimal enhancement in hBMSCs differentiation. After being implanted in rat tibial defects, 4-HA/CPC group exhibited better bone repair ability and bone growth promoting factors, comparing to pure CPC and 1-HA/CPC groups. The underlying biological mechanism of this stimulation for HA/CPC may be on account of higher osteogenic promoting factors secretion and osteogenic genes expression with hyaluronic acid incorporation. These results indicate that hyaluronic acid is a highly anticipated additive to improve physicochemical properties and osteoinductivity performance of CPCs for minimally invasive healing of bone defects.

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