Institute for Physical Chemistry , Ruprecht-Karl-University of Heidelberg , Heidelberg 69120 , Germany ; Max Planck Institute for Intelligent Systems , Stuttgart 70569 , Germany.
Institute for Complex Materials , IFW Dresden , PO Box 270116, Dresden 01171 , Germany.
Interface Focus. 2014 Feb 6;4(1):20130046. doi: 10.1098/rsfs.2013.0046.
Multi-potent adult mesenchymal stem cells (MSCs) derived from bone marrow have therapeutic potential for bone diseases and regenerative medicine. However, an intrinsic heterogeneity in their phenotype, which in turn results in various differentiation potentials, makes it difficult to predict the response of these cells. The aim of this study is to investigate initial cell-surface interactions of human MSCs on modified titanium alloys. Gold nanoparticles deposited on β-type Ti-40Nb alloys by block copolymer micelle nanolithography served as nanotopographical cues as well as specific binding sites for the immobilization of thiolated peptides present in several extracellular matrix proteins. MSC heterogeneity persists on polished and nanopatterned Ti-40Nb samples. However, cell heterogeneity and donor variability decreased upon functionalization of the gold nanoparticles with cyclic RGD peptides. In particular, the number of large cells significantly decreased after 24 h owing to the arrangement of cell anchorage sites, rather than peptide specificity. However, the size and number of integrin-mediated adhesion clusters increased in the presence of the integrin-binding peptide (cRGDfK) compared with the control peptide (cRADfK). These results suggest that the use of integrin ligands in defined patterns could improve MSC-material interactions, not only by regulating cell adhesion locally, but also by reducing population heterogeneity.
多能成体间充质干细胞（MSCs）来源于骨髓，具有治疗骨疾病和再生医学的潜力。然而，其表型的固有异质性，进而导致各种分化潜能，使得难以预测这些细胞的反应。本研究旨在研究人 MSCs 对改性钛合金的初始细胞表面相互作用。通过嵌段共聚物胶束纳米光刻术在β型 Ti-40Nb 合金上沉积的金纳米粒子作为纳米形貌线索以及固定几种细胞外基质蛋白中存在的硫醇肽的特异性结合位点。在抛光和纳米图案化 Ti-40Nb 样品上，MSC 异质性仍然存在。然而，在用环 RGD 肽功能化金纳米粒子后，细胞异质性和供体变异性降低。特别是，由于细胞附着位点的排列，而不是肽特异性，在 24 小时后大细胞的数量明显减少。然而，与对照肽（cRADfK）相比，在存在整合素结合肽（cRGDfK）时，整合素介导的粘附簇的大小和数量增加。这些结果表明，在定义的模式中使用整合素配体不仅可以通过局部调节细胞粘附，而且可以减少群体异质性，从而改善 MSC-材料相互作用。
