3D printing technologies for Non-Small Cell Lung Cancer (NSCLC) modeling

Lung cancer is the leading cause of cancer-related death worldwide. Among the various types of lung cancer, adenocarcinoma is the most common. Although murine models are valuable tools in oncology research, species differences and ethical issues have led to their replacement with 2D systems. However, 2D models lack all the stimuli that control cell growth, differentiation and cell-cell interactions. In recent years, various 3D in vitro systems have been developed using different technologies to better understand the cellular and molecular characteristics of tumors and drug responses. 3D bioprinting technology has revolutionized tissue bioengineering, offering new methods for creating complex biomimetic tissue models. This thesis focuses on several scientific studies that analyze different 3D printing techniques for the fabrication of 3D lung models using biocompatible materials. In particular, challenges and opportunities related to the use of bioinks able to support cellular viability and functionality have been explored, as well as the capability of the inks in maintaining the mechanical properties necessary for printing and handling. A promising candidate for the development of matrices is GelMA (Gelatin Methacryloyl), a hydrogel widely used in 3D bioprinting due to its excellent biocompatibility and printability. Different GelMA synthesis procedures were analyzed, evaluating the homogeneity, the mechanical properties, and cellular compatibility of the final hydrogels. Finally, new 3D-printed in vitro models for studying lung cancer stem cells were developed and introduced. Overall, the results highlighted in this thesis demonstrated the advances in 3D-printed tumor models and their advantages in replicating tumor complexity and regulating cell behavior, compared to 2D models.