Hydrogel scaffolds to study cell biology in four dimensions

Hydrogel scaffolds to study cell biology in four dimensions
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DOI:
10.1557/mrs.2013.54
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发表时间:
2013-03-01
期刊:
影响因子:
5
通讯作者:
Anseth, Kristi S.
Anseth, Kristi S.
中科院分区:
材料科学3区
文献类型:
--
作者:
Lewis, Katherine J. R.;Anseth, Kristi S.

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聚(乙二醇)(PEG)水凝胶代表了一种用于二维或三维培养细胞的通用材料支架,具有有限的蛋白质污染和细胞相容性聚合的优点,以实现细胞包封。通过使用基于光的化学用于凝胶化和用于将生物分子并入网络中,可以创建动态小生境,以便于研究细胞如何响应环境信号中的用户指示或细胞指示的变化。具体而言,我们证明了整合的光可裂解的分子到网络的交联和到悬垂的官能团,以构建凝胶的生物物理和生化特性,是时空可调的光。与这种方法互补的是,可以在水凝胶网络内引入酶促可切割的肽序列,在这种情况下,通过含硫醇的生物大分子和含烯的合成聚合物之间的光引发的加成反应,以使其周围的水凝胶微环境的细胞重塑成为可能。有了这样的可调材料平台,研究人员可以采用系统的方法进行3D细胞培养实验,在空间和时间上调节物理特性(例如,硬度)以及生物信号(例如,粘附配体)来研究细胞对环境刺激的反应。总的来说,这些材料系统为研究和操纵四维细胞功能的新实验提供了途径。
Poly(ethylene glycol) (PEG) hydrogels represent a versatile material scaffold for culturing cells in two or three dimensions with the advantages of limited protein fouling and cytocompatible polymerization to enable cell encapsulation. By using light-based chemistries for gelation and for incorporating biomolecules into the network, dynamic niches can be created that facilitate the study of how cells respond to user-dictated or cell-dictated changes in environmental signals. Specifically, we demonstrate integration of a photo-cleavable molecule into network cross-links and into pendant functional groups to construct gels with biophysical and biochemical properties that are spatiotemporally tunable with light. Complementary to this approach, an enzymatically cleavable peptide sequence can be introduced within hydrogel networks, in this case through photoinitiated addition reactions between thiol-containing biomacromolecules and ene-containing synthetic polymers, to enable cellular remodeling of their surrounding hydrogel microenvironment. With such tunable material platforms, researchers can employ a systematic approach for 3D cell culture experiments, spatially and temporally modulating physical properties (e.g., stiffness) as well as biological signals (e.g., adhesive ligands) to study cell behavior in response to environmental stimuli. Collectively, these material systems suggest routes for new experimentation to study and manipulate cellular functions in four dimensions.