Construction of 3D-tumor model for drug screening:Application of microfluidics

Abstract

<p indent=0mm>Indeed, drug screening is employed for the purpose of scanning the efficacy of growth inhibitors or killing phenotype-oriented cells towards exploring the efficacy of chemotherapeutic agents. To explore this aspect of testing, various tools have been established, such as two-dimensional (2D) monolayer and three-dimensional (3D) culture models, which suffer from various limitations of time-consuming, failed to explore the PK-PD attributes in animals. To this end, various 3D tumor models have been fabricated to reproduce the corresponding drug sensitivity and resistance within the tumor aggregation <italic>in vivo</italic>, improving the accuracy of standard anticancer drug screening. Specifically, the 3D tumor model can be employed to mimic the dynamic reciprocity of the tumor microenvironment and overcome the shortcomings concerning genotype, phenotype, and so forth. Furthermore, the biomaterials, namely scaffold-based 3D cancer models, have been designed with various properties to explore particular cues <italic>in vivo</italic>. The integrated TMEs possess cell-cell and cell-matrix interaction, which can be reproduced <italic>in vitro</italic> using different natural or synthetic materials. Cell-cell interactions are of great vitality for malignant tumors and can significantly affect the development of neoplastic cells. Endothelial cells in TMEs, where the hypoxia is given rise by close-grained structure, can be induced to facilitate angiogenesis. In addition, cancer-associated fibroblasts give rise to abnormal ECM content. Moreover, the tumorigenesis at the same time influences the physicochemical TMEs, where cell-matrix interaction incorporates gradient of the gas, stiffness around the cellular component. Together, the intricate TME allows the researchers to mimic target properties in virtue of the static 3D tumor model, although the carcinogenic effect or the progress of cancer locate a dynamic condition, which partly leads to drug screening inaccuracy. Accordingly, the application of microfluidics, to a considerable extent, enhances the accuracy in fabricating 3D tumor models, which have gained enormous development in the field of tissue engineering and drug screening due to the excellent feasibility in simulating 3D tumor models. On the one hand, the microfluidic technology is characterized by laminar flow in the channel, where the stream of the fluid can be paralleled with default flow direction, and the only diffusion may be existed inside the passage, resulting in the controllable mass transfer. On the other hand, many blood vessels, as well as physical gradient, can be easily achieved. Additionally, the microfluidic chip is likewise emphasized by the ability of integration, which is employed to enrich the function. Consequently, coupled with a scaffold-based 3D tumor model, the researchers have established various intensive models with respect to vascularization, migration, and metastasis of cancer. To further facilitate the superiority of this prospective field, with respect to perfusion and vascularization, coculture and gradient, as well as the advanced approaches to fabricate the scaffold in virtue of microfluidics, the developmental proposals are systemically discussed in this review. Firstly, the complicated composition of TMEs will be elaborated, and then put the eyesight on the development and prospective in scaffold-based tumor model on a chip.