Epithelial organoids are most efficiently grown from mouse-tumour-derived, reconstituted extracellular matrix hydrogels, whose poorly defined composition, batch-to-batch variability and immunogenicity limit clinical applications. Efforts to replace such ill-defined matrices for organoid culture have largely focused on non-adaptable hydrogels composed of covalently crosslinked hydrophilic macromolecules. However, the excessive forces caused by tissue expansion in such elastic gels severely restrict organoid growth and morphogenesis. Chemical or enzymatic degradation schemes can partially alleviate this problem, but due to their irreversibility, long-term applicability is limited. Here we report a family of synthetic hydrogels that promote extensive organoid morphogenesis through dynamic rearrangements mediated by reversible hydrogen bonding. These tunable matrices are stress relaxing and thus promote efficient crypt budding in intestinal stem-cell epithelia through increased symmetry breaking and Paneth cell formation dependent on yes-associated protein 1. As such, these well-defined gels provide promising versatile matrices for fostering elaborate in vitro morphogenesis.

上皮类器官最有效地从小鼠肿瘤衍生的重组细胞外基质水凝胶中生长出来，其成分定义不明确、批次间的变异性和免疫原性限制了临床应用。取代这种用于类器官培养的不明确基质的努力主要集中在由共价交联的亲水性大分子组成的非适应性水凝胶上。然而，在这种弹性凝胶中由组织膨胀引起的过度力严重限制了类器官的生长和形态发生。化学或酶降解方案可以部分缓解这一问题，但由于其不可逆性，长期适用性受到限制。在这里，我们报告了一个合成水凝胶家族，它们通过可逆氢键介导的动态重排促进广泛的类器官形态发生。