3D Bioprinting for In Vitro Models of Oral Cancer: Toward Development and Validation.

The tumor microenvironment (TME) of oral carcinomas has highly complex contents and a dynamic nature which is difficult to study using oversimplified two-dimensional (2D) cell culture systems. By contrast, three dimensional (3D) in vitro models such as spheroids, organoids, and scaffold-based constructs have been able to replicate tumors three-dimensionality and have allowed a better understanding of the role of various microenvironmental cues in the initiation and progression of cancer. However, the heterogeneity of TME cannot be fully reproduced by these traditional tissue engineering strategies since they are unable to control the organization of multiple cell types in a complex architecture. 3D bioprinting is an emerging field that can be leveraged to produce biomimetic and complex tissue structures. Bioprinting allows for controllable and precise placement of multicomponent bioinks composed of multiple biomaterials, different types of cells, and soluble factors according to the natural compartments of the target tissue, aiming to reproduce the equivalent of the complex tissue. As such, 3D bioprinting provides a unique opportunity to fabricate in vitro tumor models with a complexity similar to that of the in vivo oral carcinoma. This will facilitate a thorough investigation of cellular physiology, cancer progression, and anti-cancer drug screening with unprecedented control and reproducibility. In this review, we discuss the role of 3D bioprinting in reconstituting oral cancer, the prospects of application to fill the literature gap, and the challenges that need to be addressed in order to exploit this emerging technology for future work in oral cancer research.