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将肝素交联至脱矿骨基质对机械强度及与人骨形态发生蛋白-2特异性结合的影响。

The effect of crosslinking heparin to demineralized bone matrix on mechanical strength and specific binding to human bone morphogenetic protein-2.

作者信息

Lin Hang, Zhao Yannan, Sun Wenjie, Chen Bing, Zhang Jing, Zhao Wenxue, Xiao Zhifeng, Dai Jianwu

机构信息

Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, China.

出版信息

Biomaterials. 2008 Mar;29(9):1189-97. doi: 10.1016/j.biomaterials.2007.11.032.

Abstract

Demineralized bone matrix (DBM) is a collagen-based scaffold, but its low mechanical strength and limited BMP-2 binding ability restrict its application in bone repair. It is known that heparin could be immobilized onto scaffolds to enhance their binding of growth factors with the heparin-binding domain. Here, we crosslinked heparin to DBM to increase its BMP-2 binding ability. To our surprise, the mechanical strength of DBM was also dramatically increased. The compression modulus of heparin crosslinked DBM (HC-DBM) have improved (seven-fold increased) under wet condition, which would allow the scaffolds to keep specific shapes in vivo. As expected, HC-DBM showed specific binding ability to BMP-2. Additional studies showed the bound BMP-2 exerted its function to induce cell differentiation on the scaffold. Subcutaneous implantation of HC-DBM carrying BMP-2 showed higher alkaline phosphatase (ALP) activity (2 weeks), more calcium deposition (4 and 8 weeks) and more bone formation than that of control groups. It is concluded that HC-DBM has increased mechanical intensity as well as specific BMP-2 binding ability; HC-DBM/BMP-2 enhances the osteogenesis and therefore could be an effective medical device for bone repair.

摘要

脱矿骨基质(DBM)是一种基于胶原蛋白的支架,但其低机械强度和有限的BMP - 2结合能力限制了其在骨修复中的应用。已知肝素可以固定在支架上,以增强其与肝素结合域的生长因子结合能力。在此,我们将肝素交联到DBM上以增加其BMP - 2结合能力。令我们惊讶的是,DBM的机械强度也显著提高。肝素交联DBM(HC - DBM)在湿态下的压缩模量有所改善(增加了七倍),这将使支架在体内保持特定形状。正如预期的那样,HC - DBM对BMP - 2表现出特异性结合能力。进一步的研究表明,结合的BMP - 2在支架上发挥其诱导细胞分化的功能。皮下植入携带BMP - 2的HC - DBM显示出比对照组更高的碱性磷酸酶(ALP)活性(2周)、更多的钙沉积(4周和8周)以及更多的骨形成。结论是,HC - DBM具有增加的机械强度以及特异性BMP - 2结合能力;HC - DBM/BMP - 2增强了成骨作用,因此可能是一种有效的骨修复医疗器械。

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