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首页> 外文期刊>Acta biomaterialia >Small peptide functionalized thiol-ene hydrogels as culture substrates for understanding valvular interstitial cell activation and de novo tissue deposition
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Small peptide functionalized thiol-ene hydrogels as culture substrates for understanding valvular interstitial cell activation and de novo tissue deposition

机译：小肽功能化的硫醇-烯水凝胶作为培养底物，用于了解瓣膜间质细胞的活化和新生组织的沉积

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摘要

A thiol-ene polymerization platform was used to synthesize peptide functionalized poly(ethylene glycol) 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 extracellular matrix (ECM)). The Young's moduli of the hydrogels varied from 28 kPa (activating, 90% myofibroblasts) to 4 kPa (non-activating, 15% myofibroblast), 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 0.8 mM was used in all formulations, while the [VGVAPG] or [P15] were varied to be lower than, equal to or higher than 0.8 mM. The substrates with 1.2 mM VGVAPG and all gels with P15 led to significantly higher αSMA expression for both stiff and soft substrates, as compared to 0.8 mM RGDS alone. Importantly, all gel conditions αSMA expression were significantly lower than tissue culture poly(styrene) (TCPS; ～4- to 10-fold difference). The ECM produced decreased significantly as the total integrin-binding peptide concentration increased, but was significantly higher than that produced 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.
机译：使用硫醇-烯聚合平台合成肽官能化的聚乙二醇水凝胶，对其进行初步表征，并通过本文介绍的理论交联密度方程与杨氏模量的理论预测进行比较。经过全面表征，该材料系统在回答特定生物学假设方面的效用已通过培养和观察主动脉瓣间隙细胞（VIC）得以证明。具体而言，这些材料用于更好地了解底物弹性和生化功能对VICα平滑肌（αSMA）表达和分泌特性（即新生细胞外基质（ECM））的作用。水凝胶的杨氏模量从28 kPa（活化的90％肌成纤维细胞）到4 kPa（非活化的15％肌成纤维细胞）不等，并且通过结合三个小粘附肽序列RGDS，VGVAPG和P15来定制生化功能。为了促进VIC粘附，在所有配方中均使用0.8 mM的基础[RGDS]，而[VGVAPG]或[P15]则更改为低于，等于或高于0.8 mM。与单独的0.8 mM RGDS相比，具有1.2 mM VGVAPG的底物和所有带有P15的凝胶均导致硬质和软质底物的αSMA表达明显更高。重要的是，所有凝胶条件下αSMA的表达均显着低于组织培养的聚苯乙烯（TCPS;相差约4至10倍）。随着整联蛋白结合肽总浓度的增加，产生的ECM明显降低，但显着高于TCPS产生的ECM。这种易于定制的材料系统提供了一个有用的培养平台，可通过隔离特定的生物学线索和观察VIC功能来提高对VIC生物学的基本了解。

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