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Sulfated Hydrogel Matrices Direct Mitogenicity and Maintenance of Chondrocyte Phenotype through Activation of FGF Signaling

机译：硫酸化水凝胶基质通过FGF信号的激活直接成骨和维持软骨细胞表型

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摘要

Deciphering the roles of chemical and physical features of the extracellular matrix (ECM) is vital for developing biomimetic materials with desired cellular responses in regenerative medicine. Here, it is demonstrated that sulfation of biopolymers, mimicking the proteoglycans in native tissues, induces mitogenicity, chondrogenic phenotype, and suppresses catabolic activity of chondrocytes, a cell type that resides in a highly sulfated tissue. Through tunable modification of alginate it is shown that increased sulfation of the microenvironment promotes fibroblast growth factor (FGF) signaling-mediated proliferation of chondrocytes in a 3D matrix independent of stiffness, swelling, and porosity. Furthermore, for the first time it is shown that a biomimetic hydrogel acts as a 3D signaling matrix to mediate a heparan sulfate/heparin-like interaction between FGF and its receptor leading to signaling cascades inducing cell proliferation, cartilage matrix production, and suppression of dedifferentiation markers. Collectively, this study reveals important insights on mimicking the ECM to guide self-renewal of cells via manipulation of distinct signaling mechanisms.
机译：破解细胞外基质（ECM）的化学和物理特征的作用对于在再生医学中开发具有所需细胞反应的仿生材料至关重要。在这里，已证明，模仿天然组织中的蛋白聚糖的生物聚合物的硫酸化可诱导有丝分裂性，软骨形成表型，并抑制软骨细胞（存在于高度硫酸化的组织中的细胞类型）的分解代谢活性。通过藻酸盐的可调节修饰，表明微环境的硫酸化增加促进了成纤维细胞生长因子（FGF）信号介导的软骨细胞在3D基质中的生长，而与刚度，膨胀和孔隙率无关。此外，首次显示仿生水凝胶充当3D信号传递基质，介导FGF和其受体之间的硫酸乙酰肝素/肝素样相互作用，导致信号传递级联反应诱导细胞增殖，软骨基质产生和去分化抑制标记。总的来说，这项研究揭示了模仿ECM通过操纵不同信号机制来指导细胞自我更新的重要见解。

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  • 来源
    《Advanced Functional Materials》 |2016年第21期|3649-3662|共14页
  • 作者

    Ozturk Ece; Arlov Oystein; Aksel Seda; Li Ling; Ornitz David M.; Skjak-Braek Gudmund; Zenobi-Wong Marcy;

  • 作者单位

    ETH, Cartilage Engn Regenerat, Otto Stern Weg 7, CH-8093 Zurich, Switzerland;

    Norwegian Univ Sci & Technol, Dept Biotechnol, Sem Saelands Vei 6-8, N-7034 Trondheim, Norway;

    ETH, Dept Mat, Polymer Technol Lab, Vladimir Prelog Weg 1-5-10, CH-8093 Zurich, Switzerland;

    Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA;

    Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA;

    Norwegian Univ Sci & Technol, Dept Biotechnol, Sem Saelands Vei 6-8, N-7034 Trondheim, Norway;

    ETH, Cartilage Engn Regenerat, Otto Stern Weg 7, CH-8093 Zurich, Switzerland;

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