van der Smissen Anja, Hoffmeister Peter-Georg, Friedrich Nadja, Watarai Akira, Hacker Michael C, Schulz-Siegmund Michaela, Anderegg Ulf
Department of Dermatology, Venereology and Allergology, Leipzig University, Germany.
Collaborative Research Centre (SFB-TR67), Matrix Engineering Leipzig and Dresden, Germany.
J Tissue Eng Regen Med. 2017 May;11(5):1390-1402. doi: 10.1002/term.2037. Epub 2015 May 26.
Surface modification of materials designed for regenerative medicine may improve biocompatibility and functionality. The application of glycosaminoglycans (GAGs) and chemically sulphated GAG derivatives is a promising approach for designing functional biomaterials, since GAGs interact with cell-derived growth factors and have been shown to support fibroblast growth in two-dimensional (2D) cultures. Here, coatings with artificial extracellular matrix (aECM), consisting of the structural protein collagen I and the GAG hyaluronan (HA) or sulphated HA derivatives, were investigated for their applicability in a three-dimensional (3D) system. As a model, macroporous poly(lactic-co-glycolic acid) (PLGA) scaffolds were homogeneously coated with aECM. The resulting scaffolds were characterized by compressive moduli of 0.9-1.2 MPa and pore sizes of 40-420 µm. Human dermal fibroblasts (dFbs) colonized these aECM-coated PLGA scaffolds to a depth of 400 µm within 14 days. In aECM-coated scaffolds, collagen I(α1) and collagen III(α1) mRNA expression was reduced, while matrix metalloproteinase-1 (MMP-1) mRNA expression was increased within 7 days, suggesting matrix-degradation processes. Stimulation with TGFβ1 generally increased cell density and collagen synthesis, demonstrating the efficiency of bioactive molecules in this 3D model. Thus, aECM with sulphated HA may modulate the effectivity of TGFβ1-induced collagen I(α1) expression, as demonstrated previously in 2D systems. Overall, the tested aECM with modified HA is also a suitable material for fibroblast growth under 3D conditions. Copyright © 2015 John Wiley & Sons, Ltd.
用于再生医学的材料进行表面改性可提高生物相容性和功能性。应用糖胺聚糖（GAGs）和化学硫酸化的GAG衍生物是设计功能性生物材料的一种有前景的方法，因为GAGs与细胞衍生的生长因子相互作用，并且已证明在二维（2D）培养中支持成纤维细胞生长。在此，研究了由结构蛋白I型胶原蛋白和GAG透明质酸（HA）或硫酸化HA衍生物组成的人工细胞外基质（aECM）涂层在三维（3D）系统中的适用性。作为模型，大孔聚（乳酸 - 乙醇酸）（PLGA）支架用aECM均匀涂层。所得支架的压缩模量为0.9 - 1.2MPa，孔径为40 - 420μm。人真皮成纤维细胞（dFbs）在14天内在这些aECM涂层的PLGA支架中定殖至400μm的深度。在aECM涂层的支架中，I型胶原蛋白（α1）和III型胶原蛋白（α1）mRNA表达降低，而基质金属蛋白酶-1（MMP-1）mRNA表达在7天内增加，表明存在基质降解过程。用TGFβ1刺激通常会增加细胞密度和胶原蛋白合成，证明了该3D模型中生物活性分子的有效性。因此，如先前在2D系统中所证明的，含硫酸化HA的aECM可能调节TGFβ1诱导的I型胶原蛋白（α1）表达的有效性。总体而言，经修饰HA的测试aECM也是3D条件下成纤维细胞生长的合适材料。版权所有©2015 John Wiley & Sons, Ltd.
