Photo-crosslinked hyaluronic acid hydrogel as a biomimic extracellular matrix to recapitulate in vivo features of breast cancer cells

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 MCF7 cell proliferation and growth in an aggregation manner. Furthermore, 3D-cultured MCF-7 cells not only upregulated 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.

Automated summary

2D cell culture fails to accurately replicate the features of real tumors, while 3D tumor models can better mimic the native tumor microenvironments. The degree of methacrylation has significant effects on the microstructure, mechanical properties, and degradation abilities of the hydrogel. The optimized hyaluronic acid hydrogel demonstrated favorable characteristics for facilitating cell proliferation and growth in a 3D culture environment.