Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics
Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics
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DOI：
10.1038/ncomms1792
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发表时间：
2012-04-01
影响因子：
16.6
通讯作者：
Burdick, Jason A.
中科院分区：
文献类型：
--
作者：
Guvendiren, Murat;Burdick, Jason A.
生物过程本质上是动态的，越来越多的证据表明，基质硬化在发育、伤口愈合和疾病过程中尤其起决定作用；然而，几乎所有的体外模型都是静态的。在这里，我们介绍了一种循序渐进的方法，即先加成，然后光介导交联法，以制备在细胞存在下变硬(例如，类似于3-30 kpa)的水凝胶，并研究了细胞对动态变硬的短期(几分钟到几小时)和长期(几天到几周)的响应。当基质变硬时，附着的人骨髓间充质干细胞的面积从类似的500至3,000微米(2)增加，并在几个小时的时间尺度上从类似的1到10 kpa表现出更大的牵引力。对于长达14天的培养，人骨髓间充质干细胞根据培养时间有选择地分化，在硬化之前或之后，成脂分化有利于后期硬化，而成骨分化有利于早期硬化。
Biological processes are dynamic in nature, and growing evidence suggests that matrix stiffening is particularly decisive during development, wound healing and disease; yet, nearly all in vitro models are static. Here we introduce a step-wise approach, addition then light-mediated crosslinking, to fabricate hydrogels that stiffen (for example, similar to 3-30 kPa) in the presence of cells, and investigated the short-term (minutes-to-hours) and long-term (days-to-weeks) cell response to dynamic stiffening. When substrates are stiffened, adhered human mesenchymal stem cells increase their area from similar to 500 to 3,000 mu m(2) and exhibit greater traction from similar to 1 to 10 kPa over a timescale of hours. For longer cultures up to 14 days, human mesenchymal stem cells selectively differentiate based on the period of culture, before or after stiffening, such that adipogenic differentiation is favoured for later stiffening, whereas osteogenic differentiation is favoured for earlier stiffening.