Recent advances on cancer-on-chip models: Development of 3D tumors and tumor microenvironment

Tumors are complex three-dimensional (3D) tissues that form in a microenvironment consisting of a heterogeneous mixture of cellular and non-cellular components. Due to the limitation of animal models, in vitro recreation of tumors has been developed for fundamental cancer studies and anticancer therapies. Compared to the 2D culture of cell monolayers, 3D-culture systems evidently show better recapitulation of architecture, tumor physiology, and cellular microenvironment. Furthermore, microfluidic devices provide better platforms to mimic the relevant cancerous features and the dynamic of tumor physiology which conventional 3D culture systems fail to recreate.

A growing body of research has been published recently in the literature, which highlights the benefits of the 3D in vitro models in microfluidic devices. This review will provide an overview of the most recent 3D in vitro models, so-called tumor-on-chip systems, with emphasis on the fabrication of 3D culture systems and tumor microenvironment in microfluidic devices. First, the fabrication methods of 3D tumors are being described, where we present the conventional spheroid formation techniques and the novel 3D bioprinting approaches. Investigation of the steps that are involved in bioprinting is being presented, and different bioinks are introduced. In the second part, the tumor microenvironment (TME) and its role in cancer progression are being introduced. Different microfluidic technologies that are developed to stimulate multiple components of TME are studied, and their interactions with tumor cells are being discussed.