Valvular interstitial cells (VICs) respond to 3D matrix interactions in a complex manner, but understanding these effects on VIC function better is important for applications ranging from valve tissue engineering to studying valve disease. Here, we encapsulated VICs in poly(ethylene glycol) (PEG) hydrogels modified with three different adhesive ligands, derived from fibronectin (RGDS), elastin (VGVAPG) and collagen-1 (P15). By day 14, VICs became significantly more elongated in RGDS-containing gels compared to VGVAPG or P15. This difference in cell morphology appeared to correlate with global matrix metalloproteinase (MMP) activity, as VICs encapsulated in RGDS-functionalized hydrogels secreted higher levels of active MMP at day 2. VIC activation to a myofibroblast phenotype was also characterized by staining for α-smooth muscle actin (αSMA) at day 14. The percentage of αSMA+ VICs in the VGVAPG gels was the highest (56%) compared to RGDS (33%) or P15 (38%) gels. Matrix deposition and composition were also characterized at days 14 and 42 and found to depend on the initial hydrogel composition. All gel formulations had similar levels of collagen, elastin and chondroitin sulphate deposited as the porcine aortic valve. However, the composition of collagen deposited by VICs in VGVAPG-functionalized gels had a significantly higher collagen-X:collagen-1 ratio, which is associated with stenotic valves. Taken together, these data suggest that peptide-functionalized PEG hydrogels are a useful system for culturing VICs three-dimensionally and, with the ability to systematically alter biochemical and biophysical properties, this platform may prove useful in manipulating VIC function for valve regeneration. Copyright © 2013 John Wiley & Sons, Ltd.

中文翻译：

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细胞-基质相互作用对 3D PEG 水凝胶中 VIC 表型和组织沉积的作用。

瓣膜间质细胞 (VIC) 以复杂的方式响应 3D 基质相互作用，但更好地了解这些对 VIC 功能的影响对于从瓣膜组织工程到研究瓣膜疾病的应用非常重要。在这里，我们将 VIC 封装在用三种不同的粘合剂配体修饰的聚（乙二醇）（PEG）水凝胶中，这些配体来自纤连蛋白（RGDS）、弹性蛋白（VGVAPG）和胶原蛋白-1（P15）。到第 14 天，与 VGVAPG 或 P15 相比，含 RGDS 的凝胶中的 VIC 显着延长。细胞形态的这种差异似乎与整体基质金属蛋白酶 (MMP) 活性相关，因为封装在 RGDS 功能化水凝胶中的 VIC 在第 2 天分泌更高水平的活性 MMP。VIC 激活成肌成纤维细胞表型的特征还在于第 14 天对 α-平滑肌肌动蛋白 (αSMA) 的染色。与 RGDS (33%) 或 P15 (33%) 相比，VGVAPG 凝胶中 αSMA+ VIC 的百分比最高 (56%)。 38%) 凝胶。基质沉积和组成也在第 14 天和第 42 天进行了表征，发现取决于初始水凝胶组成。所有凝胶制剂的胶原蛋白、弹性蛋白和硫酸软骨素含量与猪主动脉瓣相似。然而，VICs 在 VGVAPG 功能化凝胶中沉积的胶原蛋白成分具有显着更高的胶原蛋白-X:胶原蛋白-1 比例，这与瓣膜狭窄有关。总之，这些数据表明肽功能化的 PEG 水凝胶是一种有用的系统，可用于三维培养 VIC，并且，由于能够系统地改变生化和生物物理特性，该平台可能被证明可用于操纵 VIC 功能以进行瓣膜再生。版权所有 © 2013 John Wiley & Sons, Ltd.