Monocyte inflammatory and matrix remodeling response modulated by grafted ECM-derived ligand concentration
Monocyte inflammatory and matrix remodeling response modulated by grafted ECM-derived ligand concentration
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DOI：
10.1002/jbm.a.32259
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发表时间：
2009-12-01
影响因子：
4.9
通讯作者：
Kao, Weiyuan John
中科院分区：
文献类型：
--
作者：
Chung, Amy S.;Waldeck, Heather;Kao, Weiyuan John
在生物材料上配体是促进和控制宿主反应的常用方法。在基于明胶和聚乙二醇二丙烯酸酯（PEGdA）的半互穿网络（sIPN）中，检查了细胞外基质（ECM）衍生肽量对单核细胞粘附以及随后的蛋白质和mRNA表达的影响。通过改变肽-PEG接枝的明胶与PEGdA的重量%比来控制sIPN表面上的肽量。我们推测，增加生物活性肽的量将调节人血液来源的单核细胞粘附，细胞因子表达和基因调控。评价单核细胞粘附、明胶降解蛋白酶基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）和促炎蛋白白细胞介素-1 β（IL-1 β）的释放以及这些蛋白的mRNA表达。我们发现具有较高表面RGD浓度的RGD-PEG接枝的sIPN显示出增加的粘附密度。MMP-2和IL-1 β蛋白释放也受配体浓度的影响，因为在较高的配体浓度下观察到蛋白浓度的初始增加。MMP-9蛋白表达呈先升高后下降再升高的趋势。随着时间的推移，观察到IL-1 β蛋白和mRNA表达降低，但在任何时间均未检测到MMP-2 mRNA，尽管MMP-2蛋白浓度显示初始爆发。因此，单核细胞的行为是由表面配体的身份与配体浓度串联调制。(C)2008 Wiley Periodicals，Inc. J Biomed Mater Res 91A：742-752，2009
Ligands presented on biomaterials are a common method to facilitate and control the host response. In a gelatin and polyethylene glycol diacrylate (PEGdA) based semi-interpenetrating network (sIPN), the effects of extracellular matrix (ECM)-derived peptide amount on monocyte adhesion and subsequent protein and mRNA expression were examined. Peptide amount on the sIPN surface was controlled by varying the wt % ratio of the peptide-PEG grafted gelatin to PEGdA. We hypothesized that increasing bioactive peptide amount would modulate human blood-derived monocyte adhesion, cytokine expression, and gene regulation. Monocyte adhesion, release of gelatin degrading proteases matrix metalloprotease-2 (MMP-2), matrix metalloprotease-9 (MMP-9), and proinflammatory protein interleukin-1 beta (IL-1 beta), and mRNA expression of these proteins were evaluated. We found RGD-PEG grafted sIPNs with higher surface RGD concentrations showed increased adherent density. MMP-2 and IL-1 beta protein release was also influenced by the ligand concentration, as initial increase in protein concentration was observed at higher ligand concentrations. MMP-9 protein showed an initial increase that subsided then increased. A decreased IL-1 beta protein and mRNA expression was observed over time but MMP-2 mRNA was not detected at any time though MMP-2 protein concentrations showed an initial burst. Hence, monocyte behavior was modulated by surface ligand identity in tandem with ligand concentration. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 91A: 742-752, 2009