Growth promoting substrates for human dermal fibroblasts provided by artificial extracellular matrices composed of collagen I and sulfated glycosaminoglycans.
Growth promoting substrates for human dermal fibroblasts provided by artificial extracellular matrices composed of collagen I and sulfated glycosaminoglycans.
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DOI：
10.1016/j.biomaterials.2011.08.025
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发表时间：
2011-12
期刊：
影响因子：
14
通讯作者：
Anja van der Smissen;V. Hintze;D. Scharnweber;S. Moeller;M. Schnabelrauch;Annett Majok;J. Simon;U. Anderegg
中科院分区：
文献类型：
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作者：
Anja van der Smissen;V. Hintze;D. Scharnweber;S. Moeller;M. Schnabelrauch;Annett Majok;J. Simon;U. Anderegg
天然细胞外基质(ECM)成分的应用是生物材料设计的一条很有前途的途径。在这里，我们研究了由I型胶原(COIL)和糖胺聚糖(GAGS)、透明质酸(HA)或硫酸软骨素(CS)组成的人工ECM(AECM)。此外，通过引入硫酸盐基团对GAG进行化学修饰，以获得低硫酸盐化和高硫酸盐化的GAG衍生物。硫酸盐基团有望结合和浓缩生长因子，提高其生物活性。本研究分析了AECM在8-48小时内对人真皮成纤维细胞(DFB)的初始黏附、增殖、ECM合成和分化的影响，结果表明，DFB的初始黏附和细胞增殖以硫酸盐依赖的方式逐渐增加。相反，高硫酸盐化的AECM COIL/HA3.0和COIL/CS3.1的ECM组分COIL和HA的合成减少。此外，COIL/HA3.0和COIL/CS3.1细胞中基质金属蛋白酶-1(MMP1)的表达在mRNA和蛋白水平均下调。成纤维细胞分化标记物α-平滑肌肌动蛋白(α-SMA)在基因水平上不受影响。由COIL和高硫化GAG组成的人工ECM被证明是一种适合于DFB黏附和增殖的生物材料，这种黏附和增殖诱导在皮肤伤口愈合的早期阶段发现的DFB的“增殖表型”。
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 α-smooth muscle actin (αSMA) 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.