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Growth promoting substrates for human dermal fibroblasts provided by artificial extracellular matrices composed of collagen I and sulfated glycosaminoglycans.

机译:由胶原蛋白I和硫酸化的糖胺聚糖组成的人工细胞外基质提供的用于人类皮肤成纤维细胞的生长促进底物。

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The application of native extracellular matrix (ECM) components is a promising approach for biomaterial design. Here, we investigated artificial ECM (aECM) consisting of collagen I (coll) and the glycosaminoglycans (GAGs) hyaluronan (HA) or chondroitin sulfate (CS). Additionally, GAGs were chemically modified by the introduction of sulfate groups to obtain low-sulfated and high-sulfated GAG derivatives. Sulfate groups are expected to bind and concentrate growth factors and improve their bioactivity. In this study we analyzed the effect of aECM on initial adhesion, proliferation, ECM synthesis and differentiation of human dermal fibroblasts (dFb) within 8-48 h. We show that initial adhesion and cell proliferation of dFb progressively increased in a sulfate dependent manner. In contrast, synthesis of ECM components coll and HA was decreased on high-sulfated aECM coll/HA3.0 and coll/CS3.1. Furthermore, the matrix metallo-proteinase-1 (MMP-1) was down-regulated on coll/HA3.0 and coll/CS3.1 on mRNA and protein level. The fibroblast differentiation marker alpha-smooth muscle actin (alphaSMA) is not affected by aECM on mRNA level. Artificial ECM consisting of coll and high-sulfated GAGs proves to be a suitable biomaterial for dFb adhesion and proliferation that induces a "proliferative phenotype" of dFb found in the early stages of cutaneous wound healing.
机译:天然细胞外基质(ECM)组件的应用是一种有前途的生物材料设计方法。在这里,我们研究了由胶原蛋白I(coll)和糖胺聚糖(GAG)透明质酸(HA)或硫酸软骨素(CS)组成的人工ECM(aECM)。另外,通过引入硫酸根基团对GAG进行化学修饰以获得低硫酸化和高硫酸化的GAG衍生物。硫酸盐基团有望结合并浓缩生长因子并改善其生物活性。在这项研究中,我们分析了aECM在8-48小时内对人皮肤成纤维细胞(dFb)初始黏附,增殖,ECM合成和分化的影响。我们表明,dFb的初始粘附和细胞增殖以硫酸盐依赖性方式逐渐增加。相反,在高硫酸化的aECM coll / HA3.0和coll / CS3.1上,ECM成分coll和HA的合成减少。此外,基质金属蛋白酶-1(MMP-1)在coll / HA3.0和coll / CS3.1的mRNA和蛋白水平下调。成纤维细胞分化标志物α-平滑肌肌动蛋白(alphaSMA)在mRNA水平上不受aECM的影响。由coll和高硫酸化GAG组成的人工ECM被证明是dFb粘附和增殖的合适生物材料,它诱导了皮肤伤口愈合早期发现的dFb的“增生表型”。

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