Stiffness and adhesivity control aortic valve interstitial cell behavior within hyaluronic acid based hydrogels.
Stiffness and adhesivity control aortic valve interstitial cell behavior within hyaluronic acid based hydrogels.
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DOI：
10.1016/j.actbio.2013.04.050
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发表时间：
2013-08
影响因子：
9.7
通讯作者：
Butcher, Jonathan T.
中科院分区：
文献类型：
--
作者：
Duan, Bin;Hockaday, Laura A.;Kapetanovic, Edi;Kang, Kevin H.;Butcher, Jonathan T.
生物活性和可生物降解的水凝胶模拟细胞外基质，调节瓣膜间质细胞(VIC)的行为，是体外研究瓣膜心脏病发病机制的三维模型系统，也是组织工程再生模板的基础。然而，水凝胶的硬度和粘附性在VIC行为中的作用仍然知之甚少。本研究报道了氧化和甲基丙烯酸化透明质酸(Me-HA和MOHA)的合成以及基于改性HA和甲基丙烯酸酯明胶(Me-Gel)的VIC包埋杂化水凝胶的研制。水凝胶的机械硬度和溶胀比可随HA的相对分子质量和前驱体溶液的浓度/组成而变化。与机械硬度较高的水凝胶相比，机械硬度较低的纯HA水凝胶中包裹的VIC表现出更多的铺展形态，并且显著上调α-平滑肌肌动蛋白的表达，表明更多的激活的肌成纤维细胞特性。在Me-HA中添加Me-Gel促进了细胞的扩散、增殖和VIC从包裹的球体中迁移，并更好地保持了VIC的成纤维细胞表型。在Me-HA和Me-HA/Me-Gel水凝胶基质中从包裹的球体迁移过程中也观察到了VIC表型转变。这些发现对于合理设计控制VIC形态的水凝胶以及调节VIC的表型和功能具有重要意义。含VIC的Me-HA/Me-Gel杂化水凝胶有望成为瓣膜组织工程支架和研究瓣膜病理生物学的三维模型。
Bioactive and biodegradable hydrogels that mimic the extracellular matrix and regulate valve interstitial cells (VIC) behavior are of great interest as three dimensional (3D) model systems for understanding mechanisms of valvular heart disease pathogenesis in vitro and the basis for regenerative templates for tissue engineering. However, the role of stiffness and adhesivity of hydrogels in VIC behavior remains poorly understood. This study reports synthesis of oxidized and methacrylated hyaluronic acid (Me-HA and MOHA) and subsequent development of hybrid hydrogels based on modified HA and methacrylated gelatin (Me-Gel) for VIC encapsulation. The mechanical stiffness and swelling ratio of the hydrogels were tunable with molecular weight of HA and concentration/composition of precursor solution. The encapsulated VIC in pure HA hydrogels with lower mechanical stiffness showed more spreading morphology comparing to stiffer counterparts and dramatically upregulated alpha smooth muscle actin expression indicating more activated myofibroblast properties. The addition of Me-Gel in Me-HA facilitated cell spreading, proliferation and VIC migration from encapsulated spheroids and better maintained VIC fibroblastic phenotype. The VIC phenotype transition during migration from encapsulated spheroids in both Me-HA and Me-HA/Me-Gel hydrogel matrix was also observed. These findings are important for the rational design of hydrogels for controlling VIC morphology, and for regulating VIC phenotype and function. The Me-HA/Me-Gel hybrid hydrogels accommodated with VIC are promising as valve tissue engineering scaffolds and 3D model for understanding valvular pathobiology.
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影响因子：
7.7
作者：
Jabbari, Esmaiel
通讯作者：
Jabbari, Esmaiel
影响因子：
14
作者：
Benton, Julie A.;Fairbanks, Benjamin D.;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
影响因子：
9
作者：
Hockaday LA;Kang KH;Colangelo NW;Cheung PY;Duan B;Malone E;Wu J;Girardi LN;Bonassar LJ;Lipson H;Chu CC;Butcher JT
通讯作者：
Butcher JT
影响因子：
6.2
作者：
Hachet, Emilie;Van Den Berghe, Helene;Auzely-Velty, Rachel
通讯作者：
Auzely-Velty, Rachel
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ