Co-modification of calcium phosphate cement to achieve rapid bone regeneration in osteoporotic femoral condyle defect with lithium and aspirin

磷酸钙水泥与锂和阿司匹林联合改性实现骨质疏松性股骨髁缺损的快速骨再生

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作者:Zhou-Shan Tao, Wan-Shu Zhou, Rou-Tian Zhang, Yang Li, Hong-Guang Xu, Shan Wei, Zheng-Yu Wang, Min Yang

Abstract

Local application of lithium or aspirin with biological scaffold has been identified as a potent means to improve bone formation. In this study, lithium and aspirin modified calcium phosphate cement (Asp-Li/CPC) was prepared, and the feasibility of this biological scaffold in the treatment of osteoporotic bone defect was observed in vivo and in vitro. In vitro experiments confirmed that Asp-Li/CPC had better ability to promote MC3T3-E1 cells differentiation into osteoblasts, osteoblast mineralization and viability, and promote cell expression of ALP, OP, RUNX-2, OC and COL-1 protein than simple CPC or lithium modified CPC by MTT, Alizarin red staining and Western blot evaluation. In vivo experiments confirmed that Asp-Li/CPC presented the strongest effect on bone regeneration and bone mineralization through the comparison with CPC group and Li/CPC group with X-ray images, Micro-CT and Histological evaluation. RT-qPCR analysis showed that Asp-Li/CPC, Li/CPC group and CPC group demonstrated increased BMP2, Smad1, OPG than the OVX group (P<0.05), while Asp-Li/CPC exhibited decreased TNF-α, IFN-γ and RANKL than the OVX group (P<0.05). Experiments in vivo and in vitro show that Asp-Li/CPC is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved by inhibiting local inflammation and through BMP-2/Smad1 and OPG/RANKL signaling pathway.

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