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首页> 外文期刊>Biomaterials >Mechanical properties, proteolytic degradability and biological modifications affect angiogenic process extension into native and modified fibrin matrices in vitro.
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Mechanical properties, proteolytic degradability and biological modifications affect angiogenic process extension into native and modified fibrin matrices in vitro.

机译:机械性能,蛋白水解降解性和生物学修饰影响血管生成过程在体外扩展为天然和修饰的纤维蛋白基质。

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摘要

During initial stages of wound healing, fibrin clots provide a three-dimensional scaffold that induces cell infiltration and regeneration. Here, L1Ig6, a ligand for alphavbeta3 integrin was covalently incorporated within fibrin matrices to explore it as a matrix-immobilized angiogenic factor. Incorporation at concentrations greater than 1渭g/ml reduced the fibrin crosslink density, as reflected by measurements of elastic modulus and swelling. The influence of crosslink density on endothelial cell process extension was characterized by modulating factor XIII concentrations in the coagulation mixture. At low incorporated concentrations of L1Ig6, it was possible to compensate gel elastic modulus via increased factor XIII, but not at high concentrations of L1Ig6. Similar findings were found when matrix swelling was analyzed. Fibrin crosslink density strongly influenced endothelial cell process extension, fewer and shorter processes were observed at high crosslink density. Matrix metalloproteinases (MMPs) were required for process extension and zymography and Western blots identified MMP-2 but not MMP-9. The amount of active MMP-2 increased for endothelial cells cultured in native and L1Ig6-modified matrices or when stimulated with VEGF-A(165). The data indicate that distinct matrix properties can be tailored such that they become biologically stimulating and respond to cellular proteolytic activities, being a prerequisite for potential use of such matrices in biomedical applications.
机译:在伤口愈合的初始阶段,血纤蛋白凝块会提供三维支架,诱导细胞浸润和再生。在这里,L1Ig6(αvbeta3整联蛋白的配体)被共价掺入血纤蛋白基质中,以将其作为基质固定的血管生成因子进行研究。如通过弹性模量和溶胀的测量所反映的,以大于1μg/ ml的浓度掺入降低了纤维蛋白交联密度。交联密度对内皮细胞过程扩展的影响通过调节凝血混合物中的因子XIII浓度来表征。在L1g6的低掺入浓度下,可以通过增加的因子XIII来补偿凝胶弹性模量,但在L1g6的高浓度下则不能。分析基质膨胀时发现了类似的发现。纤维蛋白交联密度强烈影响内皮细胞的过程扩展,在高交联密度下观察到越来越少的过程。基质金属蛋白酶(MMPs)是过程扩展和酶谱分析所必需的,Western印迹法可识别MMP-2,但不能识别MMP-9。在天然和L1Ig6修饰的基质中或在VEGF-A刺激下培养的内皮细胞,活性MMP-2的量增加(165)。数据表明,可以对不同的基质性质进行调整,以使其变得生物学刺激并响应细胞蛋白水解活性,这是在生物医学应用中潜在使用此类基质的先决条件。

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