Synthetically sulfated hyaluronan derivatives were shown to facilitate osteogenic differentiation of human bone marrow stromal cells (hBMSC) by application in solution or incorporated in thin collagen-based coatings. In the presented study, using a biomimetic three-dimensional (3D) cell culture model based on fibrillary collagen I (3D Col matrix), we asked on the impact of binding mode of low sulfated hyaluronan (sHA) in terms of adsorptive and covalent binding on osteogenic differentiation of hBMSC. Both binding modes of sHA induced osteogenic differentiation. Although for adsorptive binding of sHA a strong intracellular uptake of sHA was observed, implicating an intracellular mode of action, covalent binding of sHA to the 3D matrix induced also intense osteoinductive effects pointing towards an extracellular mode of action of sHA in osteogenic differentiation. In summary, the results emphasize the relevance of fibrillary 3D Col matrices as a model to study hBMSC differentiation in vitro in a physiological-like environment and that sHA can display dose-dependent osteoinductive effects in dependence on presentation mode in cell culture scaffolds.

中文翻译：

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低硫酸化透明质酸与3D胶原基质结合方式对其人骨髓基质细胞成骨诱导作用的影响

合成硫酸化的透明质酸衍生物通过在溶液中应用或掺入薄的胶原基涂层中来促进人骨髓基质细胞 (hBMSC) 的成骨分化。在本研究中，我们使用基于纤维胶原 I（3D Col 基质）的仿生三维 (3D) 细胞培养模型，询问低硫酸化透明质酸 (sHA) 的结合模式对吸附和共价结合的影响hBMSC的成骨分化。sHA的两种结合模式均诱导成骨分化。尽管对于 sHA 的吸附结合，观察到 sHA 的强烈细胞内摄取，暗示细胞内作用模式，sHA 与 3D 基质的共价结合还诱导了强烈的骨诱导作用，这表明 sHA 在成骨分化中的细胞外作用模式。总之，结果强调了纤维状 3D Col 矩阵作为研究 hBMSC 分化模型的相关性体外在类似生理的环境中，sHA 可以根据细胞培养支架中的呈递模式显示出剂量依赖性的骨诱导作用。