Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore.
Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, 15 Kent Ridge Crescent, Singapore 119276, Singapore; National University of Singapore (Suzhou) Research Institute, Suzhou, Jiangsu 215000, China; National University of Singapore (Chongqing) Research Institute, Yubei District, Chongqing 401120, China.
Carbohydr Polym. 2024 Sep 1;339:122253. doi: 10.1016/j.carbpol.2024.122253. Epub 2024 May 11.
In vitro tumor models are essential for understanding tumor behavior and evaluating tumor biological properties. Hydrogels that can mimic the tumor extracellular matrix have become popular for creating 3D in vitro tumor models. However, designing biocompatible hydrogels with appropriate chemical and physical properties for constructing tumor models is still a challenge. In this study, we synthesized a series of β-cyclodextrin (β-CD)-crosslinked polyacrylamide hydrogels with different β-CD densities and mechanical properties and evaluated their potential for use in 3D in vitro tumor model construction, including cell capture and spheroid formation. By utilizing a combination of β-CD-methacrylate (CD-MA) and a small amount of N,N'-methylene bisacrylamide (BIS) as hydrogel crosslinkers and optimizing the CD-MA/BIS ratio, the hydrogels performed excellently for tumor cell 3D culture and spheroid formation. Notably, when we co-cultured L929 fibroblasts with HeLa tumor cells on the hydrogel surface, co-cultured spheroids were formed, showing that the hydrogel can mimic the complexity of the tumor extracellular matrix. This comprehensive investigation of the relationship between hydrogel mechanical properties and biocompatibility provides important insights for hydrogel-based in vitro tumor modeling and advances our understanding of the mechanisms underlying tumor growth and progression.
体外肿瘤模型对于理解肿瘤行为和评估肿瘤生物学特性至关重要。能够模拟肿瘤细胞外基质的水凝胶已成为构建 3D 体外肿瘤模型的热门选择。然而，设计具有适当化学和物理性质的生物相容性水凝胶用于构建肿瘤模型仍然是一个挑战。在这项研究中，我们合成了一系列具有不同 β-环糊精（β-CD）密度和机械性能的β-CD 交联聚丙烯酰胺水凝胶，并评估了它们在 3D 体外肿瘤模型构建中的应用潜力，包括细胞捕获和球体形成。通过将β-CD-甲基丙烯酰胺（CD-MA）与少量 N,N'-亚甲基双丙烯酰胺（BIS）组合用作水凝胶交联剂，并优化 CD-MA/BIS 比例，水凝胶在肿瘤细胞 3D 培养和球体形成方面表现出色。值得注意的是，当我们在水凝胶表面共培养 L929 成纤维细胞和 HeLa 肿瘤细胞时，形成了共培养球体，表明水凝胶可以模拟肿瘤细胞外基质的复杂性。这项对水凝胶机械性能和生物相容性之间关系的综合研究为基于水凝胶的体外肿瘤建模提供了重要的见解，并推进了我们对肿瘤生长和进展机制的理解。
