A Protein‐Adsorbent Hydrogel with Tunable Stiffness for Tissue Culture Demonstrates Matrix‐Dependent Stiffness Responses
A Protein‐Adsorbent Hydrogel with Tunable Stiffness for Tissue Culture Demonstrates Matrix‐Dependent Stiffness Responses
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用于组织培养的具有可调刚度的蛋白质吸附水凝胶展示了基质依赖性刚度响应
DOI：
10.1002/adfm.202309567
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发表时间：
2024
影响因子：
19
通讯作者：
Chen, Christopher S.
中科院分区：
文献类型：
--
作者：
Li, Linqing;Griebel, Megan E.;Uroz, Marina;Bubli, Saniya Yesmin;Gagnon, Keith A.;Trappmann, Britta;Baker, Brendon M.;Eyckmans, Jeroen;Chen, Christopher S.
尽管组织培养塑料已广泛用于细胞培养，但塑料的刚性不是生理性的。用于培养细胞的较软的水凝胶尚未被广泛采用，部分原因是需要偶联化学来共价捕获细胞外基质（ECM）蛋白并支持细胞粘附。为了创建具有可调刚度的体外系统，该系统易于吸附用于细胞培养的ECM蛋白，通过将葡聚糖主链上的羟基残基化学转化为甲基丙烯酸酯基团，从而将非蛋白质粘合剂、亲水性葡聚糖转化为高度蛋白质吸附剂基质，提出了一种新型疏水水凝胶系统。增加甲基丙烯酸酯官能度增加了所得水凝胶的疏水性，并增强了ECM蛋白吸附，而无需额外的化学反应。这些疏水性水凝胶允许不依赖于疏水性或ECM涂层的基底刚度的容易且可调的调节。使用这种方法，它表明，基板刚度和ECM吸附一起工作，影响细胞形态和增殖，但这些影响的强度在不同的细胞类型。此外，还揭示了硬度介导的真皮成纤维细胞向肌成纤维细胞的分化受到底物ECM的调节。该材料系统显示出显著的简单性和灵活性，以调整ECM涂层和基底刚度，并研究它们对细胞功能的影响。
Although tissue culture plastic has been widely employed for cell culture, the rigidity of plastic is not physiologic. Softer hydrogels used to culture cells have not been widely adopted in part because coupling chemistries are required to covalently capture extracellular matrix (ECM) proteins and support cell adhesion. To create an in vitro system with tunable stiffnesses that readily adsorbs ECM proteins for cell culture, a novel hydrophobic hydrogel system is presented via chemically converting hydroxyl residues on the dextran backbone to methacrylate groups, thereby transforming non‐protein adhesive, hydrophilic dextran to highly protein adsorbent substrates. Increasing methacrylate functionality increases the hydrophobicity in the resulting hydrogels and enhances ECM protein adsorption without additional chemical reactions. These hydrophobic hydrogels permit facile and tunable modulation of substrate stiffness independent of hydrophobicity or ECM coatings. Using this approach, it is shown that substrate stiffness and ECM adsorption work together to affect cell morphology and proliferation, but the strengths of these effects vary in different cell types. Furthermore, it is revealed that stiffness‐mediated differentiation of dermal fibroblasts into myofibroblasts is modulated by the substrate ECM. The material system demonstrates remarkable simplicity and flexibility to tune ECM coatings and substrate stiffness and study their effects on cell function.