Xue Bin, Xu Zhengyu, Li Lan, Guo Kaiqiang, Mi Jing, Wu Haipeng, Li Yiran, Xie Chunmei, Jin Jing, Xu Juan, Jiang Chunping, Gu Xiaosong, Qin Meng, Jiang Qing, Cao Yi, Wang Wei
Collaborative Innovation Center of Advanced Microstructures, National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, China.
Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China.
Nat Commun. 2025 Apr 16;16(1):3633. doi: 10.1038/s41467-025-59016-6.
Hydrogels are extensively utilized in stem cell-based tissue regeneration, providing a supportive environment that facilitates cell survival, differentiation, and integration with surrounding tissues. However, designing hydrogels for regenerating hard tissues like bone presents significant challenges. Here, we introduce macroporous hydrogels with spatiotemporally programmed mechanical properties for stem cell-driven bone regeneration. Using liquid-liquid phase separation and interfacial supramolecular self-assembly of protein fibres, the macroporous structure of hydrogels provide ample space to prevent contact inhibition during proliferation. The rigid protein fibre-coated pore shell provides sustained mechanical cues for guiding osteodifferentiation and protecting against mechanical loads. Temporally, the hydrogel exhibits tunable degradation rates that can synchronize with new tissue deposition to some extent. By integrating localized mechanical heterogeneity, macroporous structures, surface chemistry, and regenerative degradability, we demonstrate the efficacy of these stem cell-encapsulated hydrogels in rabbit and porcine models. This marks a substantial advancement in tailoring the mechanical properties of hydrogels for stem cell-assisted tissue regeneration.
水凝胶被广泛应用于基于干细胞的组织再生，提供一个支持性环境，促进细胞存活、分化以及与周围组织整合。然而，设计用于再生像骨骼这样的硬组织的水凝胶面临重大挑战。在此，我们引入具有时空编程机械性能的大孔水凝胶用于干细胞驱动的骨再生。利用蛋白质纤维的液 - 液相分离和界面超分子自组装，水凝胶的大孔结构提供了充足空间以防止增殖过程中的接触抑制。刚性蛋白质纤维包被的孔壳为引导成骨分化和抵御机械负荷提供持续的机械信号。在时间上，水凝胶表现出可调节的降解速率，能在一定程度上与新组织沉积同步。通过整合局部机械异质性、大孔结构、表面化学和再生降解性，我们在兔和猪模型中证明了这些封装干细胞的水凝胶的有效性。这标志着在为干细胞辅助组织再生定制水凝胶机械性能方面取得了重大进展。
