Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment
Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment
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DOI：
10.1016/j.biomaterials.2012.10.015
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发表时间：
2013-01-01
期刊：
影响因子：
14
通讯作者：
Ossipov, Dmitri A.
中科院分区：
文献类型：
--
作者：
Kisiel, Marta;Martino, Mikael M.;Ossipov, Dmitri A.
虽然人骨形态发生蛋白-2（rhBMP-2）是一种有前途的骨再生生长因子，但其临床疗效最近显示低于预期。为了改善rhBMP-2的临床转化，人们有强烈的动机设计更好的输送系统。透明质酸（HA）水凝胶是一种合适的载体，用于输送rhBMP-2，但这种支架的主要限制是其低细胞粘附特性。在这项研究中，我们已经确定了是否共价接枝的整合素特异性配体到HA水凝胶可以提高细胞附着，并进一步增强rhBMP-2的成骨潜力。将含有全长FN的主要整合素结合结构域（FN III 9 *-10）的结构稳定的纤连蛋白（FN）片段工程化，以便掺入HA水凝胶中。与未功能化的HA水凝胶相比，HA-FN水凝胶显著提高了材料支持间充质干细胞附着和铺展的能力。在大鼠异位骨形成模型中，与在非功能化HA水凝胶中递送生长因子相比，用HA-FN水凝胶递送rhBMP-2导致形成两倍多的骨，具有更好的胶原纤维组织。这种rhBMP-2的工程化水凝胶载体可用于临床骨修复。(C)2012爱思唯尔有限公司保留所有权利。
While human bone morphogenetic protein-2 (rhBMP-2) is a promising growth factor for bone regeneration, its clinical efficacy has recently shown to be below expectation. In order to improve the clinical translation of rhBMP-2, there exists strong motivation to engineer better delivery systems. Hyaluronic acid (HA) hydrogel is a suitable carrier for the delivery of rhBMP-2, but a major limitation of this scaffold is its low cell adhesive properties. In this study, we have determined whether covalent grafting of an integrin-specific ligands into HA hydrogel could improve cell attachment and further enhance the osteogenic potential of rhBMP-2. A structurally stabilized fibronectin (FN) fragment containing the major integrin-binding domain of full-length FN (FN III9*-10) was engineered, in order to be incorporated into HA hydrogel. Compared to non-functionalized HA hydrogel, HA-FN hydrogel remarkably improved the capacity of the material to support mesenchymal stem cell attachment and spreading. In an ectopic bone formation model in the rat, delivery of rhBMP-2 with HA-FN hydrogel resulted in the formation of twice as much bone with better organization of collagen fibers compared to delivering the growth factor in non-functionalized HA hydrogel. This engineered hydrogel carrier for rhBMP-2 can be relevant in clinical bone repair. (C) 2012 Elsevier Ltd. All rights reserved.