Small peptide functionalized thiol-ene hydrogels as culture substrates for understanding valvular interstitial cell activation and de novo tissue deposition.
Small peptide functionalized thiol-ene hydrogels as culture substrates for understanding valvular interstitial cell activation and de novo tissue deposition.
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DOI：
10.1016/j.actbio.2012.05.009
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发表时间：
2012-09
影响因子：
9.7
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
Gould, Sarah T.;Darling, Nicole J.;Anseth, Kristi S.
利用巯基 - 烯聚合平台合成了肽功能化聚乙二醇（PEG）水凝胶，首先对其进行了表征，并通过本文提出的理论交联密度方程与杨氏模量的理论预测值进行了比较。经过全面表征后，通过对主动脉瓣间质细胞（VICs）的培养和观察，证明了该材料体系在解答特定生物学假设方面的实用性。具体而言，这些材料被用于更好地理解基质弹性和生化功能在VICα - 平滑肌肌动蛋白（αSMA）表达及分泌特性（即新生细胞外基质）方面的作用。水凝胶的杨氏模量在28kPa（激活态，90%肌成纤维细胞）到4kPa（非激活态，15%肌成纤维细胞）的基质之间变化，并且通过引入三种小的黏附肽序列RGDS、VGVAPG和P15来调整生化功能。为了促进VIC黏附，在所有配方中使用0.8mM的基础[RGDS]浓度，同时将[VGVAPG]或[P15]浓度设置为低于、等于或高于0.8mM。与单独使用0.8mM的RGDS相比，含有1.2mM VGVAPG的基质以及所有含P15的凝胶在刚性和软性基质上均导致αSMA表达显著升高。重要的是，所有凝胶条件下的αSMA表达均显著低于组织培养聚苯乙烯（TCPS）（约4 - 10倍差异）。随着整合素结合肽总浓度的增加，产生的细胞外基质显著减少，但仍显著高于在TCPS上表达的量。这种易于调整的材料体系提供了一个有用的培养平台，通过分离特定的生物信号并观察VIC功能，增进对VIC生物学的基本理解。
A thiol-ene polymerization platform was used to synthesize peptide functionalized poly(ethylene glycol) (PEG) hydrogels, which were initially characterized and compared to theoretical predictions of Young’s modulus via a theoretical crosslinking density equation presented herein. After thorough characterization, this material system’s utility for answering specific biological hypotheses was demonstrated with the culture and observation of aortic valvular interstitial cells (VICs). Specifically, these materials were used to better understand the role of substrate elasticity and biochemical functionality on VIC α-smooth muscle (αSMA) expression and secretory properties (i.e., de novo ECM). The Young’s moduli of the hydrogels were varied from 28kPa (activating, 90% myofibroblasts) to 4kPa (non-activating, 15% myofibroblast) substrates, and the biochemical functionality was tailored by incorporating three small adhesive peptide sequences, RGDS, VGVAPG, and P15. To promote VIC adhesion, a basal [RGDS] of 0.8mM was used in all formulations, while the [VGVAPG] or [P15] were varied to be lower, equal, or higher than 0.8mM. The substrates with 1.2mM VGVAPG and all gels with P15 led to significantly higher αSMA expression for both stiff and soft substrates, as compared to 0.8mM RGDS alone. Importantly, all gel conditions were significantly lower than TCPS (~4–10 fold difference). The ECM produced significantly decreased as the total integrin binding peptide concentration increased, but was significantly higher than that expressed on TCPS. This easily tailored material system provides a useful culture platform to improve the fundamental understanding of VIC biology through isolating specific biological cues and observing VIC function.
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影响因子：
14
作者：
Benton, Julie A.;Fairbanks, Benjamin D.;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
DOI：
10.1098/rstb.2007.2126
发表时间：
2007-08-29
影响因子：
6.3
作者：
Chester, Adrian H.;Taylor, Patricia M.
通讯作者：
Taylor, Patricia M.
影响因子：
6.9
作者：
Cushing, MC;Liao, JT;Anseth, KS
通讯作者：
Anseth, KS
影响因子：
6.2
作者：
Lutolf, MP;Hubbell, JA
通讯作者：
Hubbell, JA
影响因子：
29.4
作者：
Fairbanks, Benjamin D;Schwartz, Michael P;Halevi, Alexandra E;Nuttelman, Charles R;Bowman, Christopher N;Anseth, Kristi S
通讯作者：
Anseth, Kristi S