Hydrogels with time-dependent material properties enhance cardiomyocyte differentiation in vitro.
Hydrogels with time-dependent material properties enhance cardiomyocyte differentiation in vitro.
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DOI：
10.1016/j.biomaterials.2010.10.020
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发表时间：
2011-02
期刊：
影响因子：
14
通讯作者：
Engler, Adam J.
中科院分区：
文献类型：
--
作者：
Young, Jennifer L.;Engler, Adam J.
组织特异性弹性模量（E）或"刚度"由细胞外基质（ECM）的发育变化引起，并表明当物理条件模拟组织进展时，祖细胞分化可能是最佳的。对于心肌细胞，从中胚层到成体心肌的成熟导致9倍的硬化，部分源于胶原蛋白表达和定位的变化。为了模拟这种时间刚度变化在体外，巯基化透明质酸水凝胶与聚（乙二醇）二丙烯酸酯交联，并通过改变交联剂分子量来调节它们的动力学。随着水凝胶在发育过程中适当地调整到心脏肌肉，在胶原包被的HA水凝胶上生长的前心脏细胞表现出成熟心脏特异性标志物的3倍增加，并且形成比在顺应性但静态聚丙烯酰胺水凝胶上生长2周时多60%的成熟肌纤维。虽然酯水解在体外2周内基本上不改变水凝胶的硬化，但模型预测表明，酯水解最终会随着时间的推移而降解材料，这意味着这种水凝胶可能适用于体内应用，其中随时间变化的材料特性在其被宿主组织替代之前增强细胞成熟。
Tissue-specific elastic modulus (E), or ‘stiffness,’ arises from developmental changes in the extracellular matrix (ECM) and suggests that progenitor cell differentiation may be optimal when physical conditions mimic tissue progression. For cardiomyocytes, maturing from mesoderm to adult myocardium results in a 9-fold stiffening originating in part from a change in collagen expression and localization. To mimic this temporal stiffness change in vitro, thiolated-hyaluronic acid hydrogels were crosslinked with poly(ethylene glycol) diacrylate, and their dynamics were modulated by changing crosslinker molecular weight. With the hydrogel appropriately tuned to stiffen as heart muscle does during development, pre-cardiac cells grown on collagen-coated HA hydrogels exhibit a 3-fold increase in mature cardiac-specific markers and form up to 60% more maturing muscle fibers than they do when grown on compliant but static polyacrylamide hydrogels over 2 weeks. Though ester hydrolysis does not substantially alter hydrogel stiffening over 2 weeks in vitro, model predictions indicate that ester hydrolysis will eventually degrade the material with additional time, implying that this hydrogel may be appropriate for in vivo applications where temporally changing material properties enhance cell maturation prior to its replacement with host tissue.
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影响因子：
3.4
作者：
Saha, Krishanu;Keung, Albert J.;Healy, Kevin E.
通讯作者：
Healy, Kevin E.
DOI：
10.1083/jcb.200405004
发表时间：
2004-09-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Engler AJ;Griffin MA;Sen S;Bönnemann CG;Sweeney HL;Discher DE
通讯作者：
Discher DE
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW
影响因子：
3.4
作者：
Guo, WH;Frey, MT;Wang, YL
通讯作者：
Wang, YL
影响因子：
2.7
作者：
Sanger, Joseph W.;Kang, Songman;Sanger, Jean M.
通讯作者：
Sanger, Jean M.