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首页> 外文期刊>Advanced Functional Materials >Low-Defect Thiol-Michael Addition Hydrogels as Matrigel Substitutes for Epithelial Organoid Derivation
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Low-Defect Thiol-Michael Addition Hydrogels as Matrigel Substitutes for Epithelial Organoid Derivation

机译：低缺陷硫醇-Michael加成水凝胶作为基质胶质替代上皮有机体衍生物

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摘要

Due to their selective crosslinking chemistry and well-defined mechano-biochemical characteristics, hydrogels crosslinked by thiol-Michael addition reactions have garnered immense interest for 3D cell culture applications. These hydrogels are typically formed via end-linking of bis-cysteine oligopeptides and branched f-functional (f = 3) poly(ethylene glycol) (PEG). Unfortunately, this gel design accumulates excessive structural defects at a solid content below approximate to 10% (w/v) due to diluted bifunctional components reacting intramolecularly to form primary loops that compromise the gels' mechanical integrity and lead to excessive swelling. These limitations restrict the suitability of the gels for challenging cell culture applications, such as the growth of organoids. Here, low-defect thiol-Michael addition (LDTM) hydrogels based on novel building blocks designed toward minimizing structural defects are reported. Compared to the conventional gels, LDTM gels can be generated at an at least 2-fold lower solid content, while still incorporating high concentrations of bioactive ligands (approximate to 3 x 10(-3) m). LDTM gels promote the efficient development of fully patterned mouse intestinal organoids as well as human intestinal organoids, the latter in the absence of any animal-derived components. Powerful alternatives are thus provided to the gold-standard Matrigel, which is expensive and too variable for robust organoid development, facilitating translational applications of organoids.
机译：由于它们的选择性交联化学和明确定义的机械化学特性，通过硫醇 - 迈克尔加法反应交联的水凝胶对3D细胞培养应用的巨大感兴趣。这些水凝胶通常通过双半胱氨酸寡肽和支链F官能（F> = 3）聚（乙二醇）（PEG）的终结形成。遗憾的是，由于稀释的双官能组分在分形稀释的双官能组分以形成浸入凝胶机械完整性并导致过度膨胀的初级环并导致过度肿胀，以稀释的双官能组分，该凝胶设计在低于近似的固体含量至10％（w / v）中累积过多的结构缺陷。这些限制限制了凝胶对挑战细胞培养应用的适用性，例如有机体的生长。这里，报道了基于设计朝向最小化结构缺陷的新建筑块的低缺陷硫醇-Michael添加（LDTM）水凝胶。与常规凝胶相比，可以以至少2倍的固体含量产生LDTM凝胶，同时仍然包含高浓度的生物活性配体（近似为3×10（-3）m）。 LDTM凝胶促进了完全被仿形的小鼠肠有器件以及人类肠道有机体的有效发展，后者在没有任何动物衍生的组分的情况下。因此，对于金标标准Matrigel提供了强大的替代方案，这对于鲁棒有机体开发的昂贵且太可变，便于有机体的平移应用。

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