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Low‐Defect Thiol‐Michael Addition Hydrogels as Matrigel Substitutes for Epithelial Organoid Derivation
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2020-06-08 , DOI: 10.1002/adfm.202000761
Saba Rezakhani 1 , Nikolce Gjorevski 1 , Matthias P. Lutolf 1
Affiliation  

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 ≈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 (≈3 × 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.

中文翻译:

低缺陷硫醇-迈克尔加成水凝胶作为上皮有机体衍生的基质胶替代品

由于其选择性的交联化学和明确的机械生化特性,通过硫醇-迈克尔加成反应交联的水凝胶引起了3D细胞培养应用的极大兴趣。这些水凝胶通常是通过双半胱氨酸寡肽和分支的f-官能团(f≥3)聚乙二醇(PEG)。不幸的是,由于稀释的双功能组分在分子内反应形成主要环,损害了凝胶的机械完整性并导致过度溶胀,因此该凝胶设计在固体含量低于约10%(w / v)时会累积过多的结构缺陷。这些限制限制了凝胶对挑战性细胞培养应用(如类器官的生长)的适用性。在此,报道了基于旨在最小化结构缺陷的新型结构单元的低缺陷硫醇-迈克尔加成(LDTM)水凝胶。与常规凝胶相比,LDTM凝胶的固含量低至少2倍,同时仍掺入高浓度的生物活性配体(≈3×10 -3 m)。LDTM凝胶可促进完全图案化的小鼠肠道类器官以及人类肠道类器官的高效开发,而后者在没有任何动物来源成分的情况下。因此,为金标准的Matrigel提供了强大的替代产品,该产品昂贵且对于稳固的类器官开发而言过于可变,从而促进了类器官的翻译应用。
更新日期:2020-06-08
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