Feng Jun, Ponomareva Polina, Liu Kunpeng, Nie Chuanxiong, Chen Rui, Haag Rainer
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, Berlin 14195, Germany.
Biomacromolecules. 2025 Jun 9;26(6):3331-3343. doi: 10.1021/acs.biomac.4c01744. Epub 2025 May 10.
Advancing cancer research depends significantly on developing accurate and reliable models that can replicate the complex tumor microenvironment. Tumor spheroids─three-dimensional clusters of cancer cells─have become crucial tools for this purpose. The overarching goal of tumor spheroid culture is to develop biomaterials that mimic the dynamic mechanical behavior of the native extracellular matrix, enabling high-fidelity culture models. In this study, we developed dynamic hydrogels based on dual-dynamic covalently cross-linked polyglycerol, using boronate bonds and Schiff-base interactions. In addition to good biocompatibility and long-term stability, the hydrogels showed tunable mechanical properties that enabled cells to actively remodel their surrounding microenvironment. This platform was used for successful 3D culture of various cancer cell lines, including HeLa, A549, HT-29, BT-474, and SK-BR-3, which were encapsulated in situ and formed 3D tumor spheroids. These results demonstrate the feasibility and versatility of our dynamic hydrogel system in supporting tumor spheroid culture.
推进癌症研究在很大程度上依赖于开发能够复制复杂肿瘤微环境的准确且可靠的模型。肿瘤球体——癌细胞的三维聚集体——已成为实现这一目标的关键工具。肿瘤球体培养的总体目标是开发能够模拟天然细胞外基质动态力学行为的生物材料，从而实现高保真培养模型。在本研究中，我们基于双动态共价交联的聚甘油开发了动态水凝胶，利用硼酸酯键和席夫碱相互作用。除了良好的生物相容性和长期稳定性外，这些水凝胶还表现出可调节的力学性能，使细胞能够主动重塑其周围的微环境。该平台成功用于多种癌细胞系的三维培养，包括HeLa、A549、HT - 29、BT - 474和SK - BR - 3，这些细胞系原位包封并形成三维肿瘤球体。这些结果证明了我们的动态水凝胶系统在支持肿瘤球体培养方面的可行性和多功能性。
