A Hybrid Peptide Amphiphile Fiber PEG Hydrogel Matrix for 3D Cell Culture
A Hybrid Peptide Amphiphile Fiber PEG Hydrogel Matrix for 3D Cell Culture
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DOI：
10.1002/adfm.201808505
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发表时间：
2019-02
影响因子：
19
通讯作者：
H. Zhan;D. Löwik
中科院分区：
文献类型：
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作者：
H. Zhan;D. Löwik
由于传统的细胞生长二维表面在当代细胞生物学中已被证明越来越不足，越来越多的研究是在三维基质上进行的，这些基质可以在许多方面更好地代表天然细胞外基质（ECM）。为了产生这种复杂的不均匀3D基质，将具有叠氮化物和（1 R，8 S，9 S）-双环[6.1.0]壬-4-炔-9-基的四臂聚乙二醇官能化以形成水凝胶基础。与这些一起，还内置了作为功能基序的基质金属蛋白酶可切割肽序列，以增加水凝胶的可降解性。此外，含有细胞结合肽序列（RGDS）的自组装肽两亲物（PA）纤维被封装在水凝胶中，以模拟ECM的天然纤维结构并刺激细胞粘附。流变学研究证实，溶解在PA纤维溶液中的聚合物形成具有可接受的机械性能（G′ = 3.8 kPa）的稳定水凝胶。此外，它表明，这种水凝胶网络是金属蛋白酶的作用下降解。最后，将混合水凝胶用于培养，并且证明当所有组分都存在时，在孵育5天后，HeLa细胞和人间充质干细胞在混合水凝胶内均显示出粘附性、良好的活力和良好的铺展形状。
Since the traditional 2D surface for cell growth has been shown to be increasingly insufficient in contemporary cell biology, more and more research is performed on 3D matrices that can better represent the natural extracellular matrix (ECM) in many aspects. To create such a complex nonuniform 3D matrix, four‐armed polyethylene glycol with azides and (1R,8S,9S)‐bicyclo[6.1.0]non‐4‐yn‐9‐yl groups is functionalized to form the hydrogel basis. Together with these, a matrix metalloproteinase cleavable peptide sequence as a functional motif is also built in to add degradability to the hydrogel. In addition, self‐assembled peptide amphiphile (PA) fibers containing a cellular binding peptide sequence (RGDS) are encapsulated in the hydrogel to mimic the natural fibrous structure of the ECM and to stimulate cell adhesion. Rheology studies confirm that the polymer dissolved in the PA fiber solution forms a stable hydrogel with acceptable mechanical properties (G′ = 3.8 kPa). In addition, it is shown that this hydrogel network is degradable under the action of a metalloproteinase enzyme. Finally, the hybrid hydrogel is used to culture and it is demonstrated that both HeLa cells and human mesenchymal stem cells show adherence, good viability, and a well‐spread shape inside the hybrid hydrogel after 5 days of incubation when all components are present.