3D printing to construct in vitro multicellular models of melanoma
Shengbo Sang, Xiaoyuan Wang, Jiahui Duan, Yanyan Cao, Zhizhong Shen, Lei Sun, Qianqian Duan, Zixian Liu
Abstract
Currently, there is a lack of suitable models for in-vitro studies of malignant melanoma and traditional single cell culture models no longer reproduce tumor structure and physiological complexity well. The tumor microenvironment is closely related to carcinogenesis and it is particularly important to understand how tumor cells interact and communicate with surrounding nonmalignant cells. Three-dimensional (3D) in vitro multicellular culture models can better simulate the tumor microenvironment due to their excellent physicochemical properties. In this study, 3D composite hydrogel scaffolds were prepared from gelatin methacrylate and polyethylene glycol diacrylate hydrogels by 3D printing and light curing techniques, and 3D multicellular in vitro tumor culture models were established by inoculating human melanoma cells (A375) and human fibroblasts cells on them. The cell proliferation, migration, invasion, and drug resistance of the 3D multicellular in vitro model was evaluated. Compared with the single-cell model, the cells in the multicellular model had higher proliferation activity and migration ability, and were easy to form dense structures. Several tumor cell markers, such as matrix metalloproteinase-9 (MMP-9), MMP-2, and vascular endothelial growth factor, were highly expressed in the multicellular culture model, which were more favorable for tumor development. In addition, higher cell survival rate was observed after exposure to luteolin. The anticancer drug resistance result of the malignant melanoma cells in the 3D bioprinted construct demonstrated physiological properties, suggesting the promising potential of current 3D printed tumor model in the development of personalized therapy, especially for discovery of more conducive targeted drugs.