Modulation of osteogenic activity of BMP-2 by cellulose and chitosan derivatives

Modulation of osteogenic activity of BMP-2 by cellulose and chitosan derivatives
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DOI:
10.1016/j.actbio.2011.08.012
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发表时间:
2012-01-01
期刊:
影响因子:
9.7
通讯作者:
Groth, T.
Groth, T.
中科院分区:
工程技术1区
文献类型:
--
作者:
Peschel, D.;Zhang, K.;Groth, T.

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以纤维素和壳聚糖为原料,分别进行硫酸化、羧化和羧甲基化,合成了结构和潜在生物活性与肝素相似的多糖。使用C2 C12成肌细胞作为测量碱性磷酸酶(ALP)活性和基因Osterix表达的模型系统,与BMP-2合作研究这些衍生物的成骨活性。诺金和Runx-2结果发现,高度硫酸化的壳聚糖显示出最强的成骨活性的所有多糖,但仅在较低的浓度,而较高的浓度是抑制性的。相比之下,具有低或中等硫酸化程度的纤维素显示出随着浓度的升高ALP活性和Osterix和Noggin的表达增加。具有高羧化程度的低硫酸化纤维素的成骨活性较低,但对细胞活力有积极影响,而羧甲基化纤维素几乎没有成骨活性。结果表明,区域选择性硫酸化以及羧化纤维素和壳聚糖具有成骨活性,这使它们成为骨组织工程应用的有趣候选者。(C)2011 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Polysaccharides with structure and potential bioactivity similar to heparin were synthesized based on cellulose which was regioselectively sulfated, carboxylated or carboxymethylated, and chitosan that was sulfated only. Osteogenic activity of these derivatives was studied in cooperation with BMP-2 using C2C12 myoblast cells as a model system measuring alkaline phosphatase (ALP) activity and the expression of the genes Osterix. Noggin and Runx-2. It was found that highly sulfated chitosan showed the strongest osteogenic activity of all polysaccharides, but only at lower concentrations, while higher concentrations were inhibitory. By contrast, cellulose with a low or intermediate degree of sulfation showed increasing ALP activity and expression of Osterix and Noggin with rising concentrations. Lower sulfated cellulose with a high degree of carboxylation was less osteogenic, but had a positive effect on cell viability, while carboxymethylated cellulose had almost no osteogenic activity. The results indicate that regioselectively sulfated as well as carboxylated cellulose and chitosan possess an osteogenic activity, which makes them interesting candidates for application in tissue engineering of bone. (C) 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.