State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China; Northwest Institute for Non-ferrous Metal Research, Xi'an 710016, China.
State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
Colloids Surf B Biointerfaces. 2022 Jan;209(Pt 2):112159. doi: 10.1016/j.colsurfb.2021.112159. Epub 2021 Oct 13.
2D cell culture is widely utilized to develop anti-cancer drugs and to explore the mechanisms of cancer tumorigenesis and development. However, the findings obtained from 2D culture often fail to provide guidance for clinical tumor treatments since it cannot precisely replicate the features of real tumors. 3D tumor models capable of recapitulating native tumor microenvironments have been proved to be a promising alternative technique. Herein, we constructed a breast tumor model from novel hyaluronic acid (HA) hydrogel which was prepared through photocrosslinking of methacrylated HA. The hydrogel was used as a biomimetic extracellular matrix to incubate MCF-7 cells. It was found that methacrylation degree had great effects on hydrogel's microstructure, mechanical performances, and liquid-absorbing and degradation abilities. Optimized hydrogel exhibited highly porous morphology, high equilibrium swelling ratio, suitable mechanical properties, and hyaluronidase-responsive degradation behavior. The results demonstrated that the HA hydrogel facilitated MCF-7 cell proliferation and growth in an aggregation manner. Furthermore, 3D-cultured MCF-7 cells not only up-regulated the expression of VEGF, bFGF and interleukin-8 but exhibited greater invasion and tumorigenesis capabilities compared with 2D-cultured cells. Therefore, the HA hydrogel is a reliable substitute for tumor model construction.
2D 细胞培养广泛用于开发抗癌药物，并探索癌症发生和发展的机制。然而，从 2D 培养中获得的发现往往不能为临床肿瘤治疗提供指导，因为它不能精确复制真实肿瘤的特征。能够重现天然肿瘤微环境的 3D 肿瘤模型已被证明是一种很有前途的替代技术。在这里，我们通过光交联甲基丙烯酰化透明质酸构建了一种新型透明质酸（HA）水凝胶的乳腺癌肿瘤模型。该水凝胶用作仿生细胞外基质来孵育 MCF-7 细胞。结果发现，甲基丙烯酰化程度对水凝胶的微观结构、力学性能、吸液和降解能力有很大影响。优化后的水凝胶具有高度多孔的形态、高平衡溶胀比、合适的力学性能和透明质酸酶响应的降解行为。结果表明，HA 水凝胶促进 MCF-7 细胞以聚集的方式增殖和生长。此外，与 2D 培养的细胞相比，3D 培养的 MCF-7 细胞不仅上调了 VEGF、bFGF 和白细胞介素-8 的表达，而且表现出更强的侵袭和致瘤能力。因此，HA 水凝胶是肿瘤模型构建的可靠替代品。
