The influence of matrix degradation and functionality on cell survival and morphogenesis in PEG-based hydrogels.
The influence of matrix degradation and functionality on cell survival and morphogenesis in PEG-based hydrogels.
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基质降解和功能对基于PEG的水凝胶中细胞存活和形态发生的影响。
DOI：
10.1002/mabi.201300044
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发表时间：
2013-08
影响因子：
4.6
通讯作者：
Lin CC
中科院分区：
文献类型：
--
作者：
Raza A;Lin CC
通过硫醇 - 降冰片烯光点击反应形成的聚乙二醇（PEG）水凝胶已在多种生物医学应用中得到使用。温和且快速的硫醇 - 降冰片烯反应能够生成多种仿生细胞外基质，用于研究三维环境中的细胞行为。如果采用合适的大分子单体和交联剂，基于硫醇 - 降冰片烯PEG的水凝胶可具有生物可降解性。先前的研究已通过实验和数学方法阐明了这些水凝胶的体外降解行为。然而，硫醇 - 烯凝胶高度可调的可降解性以及不同形式的凝胶降解对促进三维环境中细胞存活和形态发生的影响尚未得到充分评估。为此，合成了两种降冰片烯功能化的PEG大分子单体，即聚乙二醇 - 四酯 - 降冰片烯（PEG4eNB）和聚乙二醇 - 四酰胺 - 降冰片烯（PEG4aNB），以使所得水凝胶具有不同的水解可降解性。使用含二硫醇的连接剂，如二硫苏糖醇或含双半胱氨酸的肽，来控制凝胶的蛋白水解可降解性。利用人间充质干细胞（hMSCs）和胰腺MIN6 β细胞评估了硫醇 - 烯凝胶可降解性对三维环境中细胞存活和形态发生的影响。结果表明，在高度交联的硫醇 - 降冰片烯水凝胶中，初始细胞活力可能会受到负面影响。此外，当细胞被包封在缺乏细胞黏附基序的硫醇 - 烯凝胶中时，在水解稳定性较差的水凝胶中，它们的存活和增殖得到促进。最后，当基质固定有细胞黏附基序并允许其进行蛋白水解和水解降解时，包封的人间充质干细胞在三维环境中的铺展程度会增强。
Poly(ethylene glycol) (PEG) hydrogels formed by thiol-norbornene photo-click reaction have been used in a variety of biomedical applications. The mild and rapid thiol-norbornene reaction permits the generation of versatile biomimetic extracellular matrices for studying cell behaviors in 3D. Thiol-norbornene PEG-based hydrogels can be rendered biodegradable if appropriate macromers and cross-linkers are employed. Previous studies have elucidated, experimentally and mathematically, in vitro degradation behaviors of these hydrogels. However, the highly tunable thiol-ene gel degradability and the influence of different forms of gel degradation on promoting cell survival and morphogenesis in 3D have not been fully evaluated. Toward this end, two norbornene-functionalized PEG macromers, namely PEG-tetra-ester-norbornene (PEG4eNB) and PEG-tetra-amide-norbornene (PEG4aNB), were synthesized to render the resulting hydrogels with different hydrolytic degradability. Di-thiol containing likers, such as dithiothreitol or bis-cysteine containing peptides, were utilized to control proteolytic degradability of the gels. The influence of thiol-ene gel degradability on cell survival and morphogenesis in 3D was assessed using human mesenchymal stem cells (hMSCs) and pancreatic MIN6 β-cells. The results showed that initial cell viability could be negatively affected in highly cross-linked thiol-norbornene hydrogels. In addition, when cells were encapsulated in thiol-ene gels lacking cell-adhesive motifs, their survival and proliferation were promoted in more hydrolytically labile hydrogels. Finally, the degree of 3D cell spreading in encapsulated hMSCs was enhanced when the matrices were immobilized with cell-adhesive motifs and were allowed to degrade both proteolytically and hydrolytically.
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影响因子：
7.7
作者：
Jabbari, Esmaiel
通讯作者：
Jabbari, Esmaiel
影响因子：
10.8
作者：
Anseth, KS;Metters, AT;Bowman, CN
通讯作者：
Bowman, CN
DOI：
10.1073/pnas.0737381100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Lutolf, MP;Lauer-Fields, JL;Hubbell, JA
通讯作者：
Hubbell, JA
影响因子：
29.4
作者：
Fairbanks, Benjamin D;Schwartz, Michael P;Halevi, Alexandra E;Nuttelman, Charles R;Bowman, Christopher N;Anseth, Kristi S
通讯作者：
Anseth, Kristi S
影响因子：
3.1
作者：
Chang, Zhi-Gang;Wei, Jun-Min;Yang, Yin-Mo
通讯作者：
Yang, Yin-Mo