Hyaluronic acid facilitates bone repair effects of calcium phosphate cement by accelerating osteogenic expression.
Hyaluronic acid facilitates bone repair effects of calcium phosphate cement by accelerating osteogenic expression.
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透明质酸通过加速成骨表达促进磷酸钙骨水泥的骨修复作用
DOI：
10.1016/j.bioactmat.2021.03.028
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发表时间：
2021-11
影响因子：
18.9
通讯作者：
Pan H
中科院分区：
文献类型：
--
作者：
Cui X;Huang C;Chen Z;Zhang M;Liu C;Su K;Wang J;Li L;Wang R;Li B;Chen D;Ruan C;Wang D;Lu WW;Pan H
磷酸钙骨水泥（CPC）因其良好的生物相容性和可降解性，被广泛认为是一种理想的骨修复替代材料，适用于骨缺损的微创治疗。然而，由于CPC的内聚性和力学性能较差，尤其是其骨诱导性较差，临床应用仍不令人满意。透明质酸增强磷酸钙骨水泥（HA/CPC）具有体外诱导潜能，不仅能提高骨水泥的抗压强度，而且能显著增强其骨诱导性。在我们的研究中，当骨水泥中加入1%的透明质酸（表示为1-HA/CPC）时，HA/CPC的抗压强度显著增加。同时，透明质酸对体外培养的人骨髓间充质干细胞（human bone marrow mesenchymal stem cells，hBMSCs）ALP活性、成骨相关蛋白及mRNA表达均有明显促进作用，其中添加4%透明质酸的HA/CPC骨水泥组（4-HA/CPC）对hBMSCs的诱导分化作用最佳。4-HA/CPC组植入大鼠胫骨缺损后，骨修复能力和骨生长促进因子均优于单纯CPC组和1-HA/CPC组。这种刺激HA/CPC的潜在生物学机制可能是由于透明质酸掺入促进了成骨促进因子分泌和成骨基因表达。这些结果表明，透明质酸是一种备受期待的添加剂，可改善CPC的理化性质和骨诱导性能，用于骨缺损的微创愈合。磷酸钙中加入透明质酸（HA）后，其综合处理性能更好. CPC中HA促进hBMSCs成骨蛋白和mRNA的表达。CPC中的HA在体内通过更高的成骨表达促进骨形成。
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. Hyaluronic acid (HA) in CPC resulted in better comprehensive handling properties. HA in CPC promoted osteogenesis protein and mRNA expression of hBMSCs. HA in CPC stimulated bone formation though higher osteogenic expression in vivo.
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