The effect of hyaluronic acid incorporation on fibroblast spreading and proliferation within PEG-diacrylate based semi-interpenetrating networks

The effect of hyaluronic acid incorporation on fibroblast spreading and proliferation within PEG-diacrylate based semi-interpenetrating networks
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DOI:
10.1016/j.biomaterials.2007.08.007
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发表时间:
2007-11-01
期刊:
影响因子:
14
通讯作者:
Webb, Ken
Webb, Ken
中科院分区:
工程技术1区
文献类型:
--
作者:
Kutty, Jaishankar K.;Cho, Eunhee;Webb, Ken

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许多合成交联水凝胶网络的纳米级网孔尺寸将包封的细胞限制为圆形形态,其可以抑制细胞过程,例如对于重塑和组织形成的早期阶段至关重要的增殖和迁移。这些研究的目的是研究一种加速细胞重塑的方法,该方法基于由可水解降解的聚(乙二醇)(PEG)二丙烯酸酯大分子单体和天然酶促降解的细胞外基质(ECM)组分(胶原蛋白、明胶和透明质酸(HA))组成的半互穿网络(IPN)的形成。在研究的三种ECM组分中,相对于不含HA的对照水凝胶,以0.12%w/v和更高的浓度添加HA支持成纤维细胞在整个三维网络中扩散并显著增加增殖。HA的掺入导致水凝胶物理/化学性质如溶胀、降解速率和弹性模量的相对较小的变化。通过加入透明质酸酶抑制剂消除了成纤维细胞扩散,表明细胞介导的HA酶促降解是导致观察到的成纤维细胞活性增加的必要机制。通过加速早期细胞重塑和生长,这些半互穿网络可能是有用的车辆细胞移植在各种组织工程应用。(c)2007爱思唯尔有限公司保留所有权利。
The nanometer-scale mesh size of many synthetic crosslinked hydrogel networks restricts encapsulated cells to a rounded morphology that can inhibit cellular processes such as proliferation and migration that are essential for the early stages of remodeling and tissue formation. The objective of these studies was to investigate an approach for accelerating cellular remodeling based on the creation of semi-interpenetrating networks (IPNs) composed of hydrolytically degradable poly(ethylene glycol) (PEG) diacrylate macromers and native, enzymatically degradable extracellular matrix (ECM) components (collagen, gelatin and hyaluronic acid (HA)). Among the three ECM components investigated, addition of HA at concentrations of 0.12% w/v and greater supported fibroblast spreading throughout the three-dimensional network and significantly increased proliferation relative to control hydrogels without HA. Incorporation of HA resulted in relatively small changes in hydrogel physical/chemical properties such as swelling, degradation rate, and elastic modulus. Fibroblast spreading was eliminated by the addition of hyaluronidase inhibitors, demonstrating that cell-mediated enzymatic degradation of HA is a necessary mechanism responsible for the observed increases in fibroblast activity. By accelerating early cellular remodeling and growth, these semi-IPNs may be useful vehicles for cell transplantation in a variety of tissue engineering applications. (c) 2007 Elsevier Ltd. All rights reserved.