A supramolecular hybrid hydrogel displaying a wide array of dynamic physical properties along with enhanced in vivo stem cell retention has been developed. The key strategy is facilely polymerizing bioactive gelatin methacrylate (GelMA) with 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA) and 2-(3-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)ureido)ethyl methacrylate (UPyMA) to generate one hybrid branched copolymer. Rapid gelation occurs upon increasing the temperature above the lower critical solution temperature (LCST) of this supramolecular copolymer, where PMEO₂MA segments dehydrate and assemble into clusters, providing a hydrophobic microenvironment facilitating UPy dimerization to connect polymer chains, thus forming quadruple hydrogen bond reinforced crosslinking networks. The biodegradable, self-healing, thermo-reversible and injectable properties of the supramolecular hydrogel are finely tunable by changing the hydrogel formulation. Mesenchymal stem cells encapsulated in the hydrogel show high viability and proliferation. The subcutaneous study shows that the stem cells delivered within the in situ formed hydrogel are well protected from mechanical damage and have significantly enhanced in vivo cell retention for three weeks. These results suggest that the dynamic supramolecular hydrogel can be utilized to regulate stem cells for tissue regeneration applications.

中文翻译：

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四个氢键和热触发的疏水相互作用产生动态水凝胶，以调节移植的细胞保留†

已经开发出显示出广泛的动态物理特性以及增强的体内干细胞保留能力的超分子杂化水凝胶。关键策略是将生物活性甲基丙烯酸明胶（GelMA）与甲基丙烯酸2-（2-甲氧基乙氧基）乙酯（MEO ₂ MA）和2-（3-（6-甲基-4-氧代-1,4-二氢嘧啶-2-甲基）（脲基）甲基丙烯酸乙酯（UPyMA）以生成一种杂化支化共聚物。当温度升高到此超分子共聚物的较低临界溶液温度（LCST）以上时，就会发生快速胶凝，其中PMEO ₂MA片段脱水并组装成团，提供了疏水性微环境，促进了UPy二聚化以连接聚合物链，从而形成了四个氢键增强的交联网络。超分子水凝胶的生物可降解，自修复，热可逆和可注射特性可通过更改水凝胶配方进行微调。包裹在水凝胶中的间充质干细胞显示出高生存力和增殖。皮下研究表明，在原位形成的水凝胶中递送的干细胞受到良好的保护，免受机械损伤，并在体内显着增强细胞保留三周。这些结果表明动态超分子水凝胶可用于调节干细胞用于组织再生应用。