Cui Xu, Huang Chengcheng, Chen Zhizhen, Zhang Meng, Liu Chunyu, Su Kun, Wang Jianyun, Li Li, Wang Renxian, Li Bing, Chen Dafu, Ruan Changshun, Wang Deping, Lu William W, Pan Haobo
Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, PR China.
Shenzhen Healthemes Biotechnology Co. Ltd, Shenzhen, 518102, PR China.
Bioact Mater. 2021 Apr 8;6(11):3801-3811. doi: 10.1016/j.bioactmat.2021.03.028. eCollection 2021 Nov.
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) , 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.
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，CPC的临床应用仍不尽人意，因为其粘结性和机械性能较差，尤其是骨诱导性。透明质酸增强磷酸钙骨水泥（HA/CPC）不仅在提高骨水泥抗压强度方面显示出巨大潜力，而且还能显著提高其骨诱导性。在我们的研究中，当骨水泥中添加1%透明质酸时（标记为1-HA/CPC），HA/CPC的抗压强度显著增加。同时，透明质酸明显促进了人骨髓间充质干细胞（hBMSCs）的碱性磷酸酶（ALP）活性、成骨相关蛋白及mRNA表达，添加4%透明质酸的HA/CPC骨水泥组（标记为4-HA/CPC）在hBMSCs分化方面表现出最佳的增强效果。与纯CPC组和1-HA/CPC组相比，植入大鼠胫骨缺损后，4-HA/CPC组表现出更好的骨修复能力和促进骨生长的因子。HA/CPC这种刺激作用的潜在生物学机制可能是由于透明质酸的掺入增加了成骨促进因子的分泌和成骨基因的表达。这些结果表明，透明质酸是一种非常有前景的添加剂，可改善CPC的物理化学性质和骨诱导性能，用于骨缺损的微创愈合。
