Close dependence of fibroblast proliferation on collagen scaffold matrix stiffness
Close dependence of fibroblast proliferation on collagen scaffold matrix stiffness
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DOI：
10.1002/term.136
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发表时间：
2009-02-01
影响因子：
3.3
通讯作者：
Brown, R. A.
中科院分区：
文献类型：
--
作者：
Hadjipanayi, E.;Mudera, V.;Brown, R. A.
自由漂浮胶原基质中的人真皮成纤维细胞（HDF）显示出最小的增殖，尽管当基质“处于张力下”时，增殖可能会增加。我们已经调查了这一重要的细胞行为的可能的控制之一，特别是假设，这是一个响应基板刚度的详细机制。将过度水合的胶原蛋白凝胶塑性压缩（PC）以得到预定的胶原蛋白密度和刚度。使用动态力学分析仪测试机械性能;通过阿利兰测定法测试细胞数量。在最硬的PC基质中，细胞增殖迅速，并具有接种密度依赖性，群体倍增时间为2天。相比之下，顺应性附着基质显示4天的滞后期和6天的倍增时间。HDF生长与基质硬度直接相关，因此使用一系列压缩水平（0-75%液体清除）增加硬度支持增加增殖率、倍增时间和基质弹性模量。HDF在顺应性基质中的静止是可逆的，因此在第1天和第5天通过压缩原位增加刚度可启动增殖。我们的结论是，胶原蛋白基质硬度调节成纤维细胞的增殖（硬反应），理解成纤维细胞-基质反馈控制在伤口愈合和工程结缔组织的胶原蛋白和其他水凝胶为基础的支架的设计和调节具有重要意义。版权所有（C）2008约翰威利父子有限公司
Human dermal fibroblasts (HDFs) in free-floating collagen matrices show minimal proliferation, although this may increase when the matrix is 'under tension'. We have investigated the detailed mechanics underlying one of the possible controls of this important cell behaviour, in particular the hypothesis that this is a response to substrate stiffness. Hyperhydrated collagen gels were plastic-compressed (PC) to give a predetermined collagen density and stiffness. Mechanical properties were tested using a dynamic mechanical analyser; cell number by Alamar blue assay. In the stiffest PC matrices, cell proliferation was rapid and seeding density-dependent, with a population doubling time of 2 days. In contrast, compliant attached matrices showed a 4 day lag period and a doubling time of 6 days. HDF growth was directly related to matrix stiffness, such that increasing stiffness using a range of compression levels (0-75% fluid removal) supported increasing proliferation rate, doubling times and matrix elastic modulus. HDF quiescence in compliant matrices was reversible, such that increasing stiffness in situ by compression at 1 and 5 days initiated proliferation. We conclude that collagen matrix stiffness regulates proliferation of fibroblasts (a duro-response), with important implications for understanding fibroblast-matrix feedback controls during wound healing and the design and regulation of engineered connective tissues based on collagen and other hydrogel-based scaffolds. Copyright (C) 2008 John Wiley & Sons, Ltd.