Biofabbricazione 3D di un modello compartimentalizzato per lo studio del microambiente tumorale

Cancer is one of the leading causes of mortality worldwide, with approximately ten million deaths annually, according to the World Health Organization. The tumor microenvironment (TME) is highly complex, characterized by a heterogeneous cellular composition and dynamic microenvironmental signals. Traditional methods for reproducing the biological environment in vitro have primarily relied on animal models and two-dimensional (2D) cultures. However, animal models are expensive and often fail to replicate critical aspects of human tissues due to biological differences between species. While some of these limitations can be overcome using 2D in vitro cultures, key features of tumors and of the TME, such as cell-cell and cell-extracellular matrix (ECM) interactions, can’t be accurately reproduced in monolayer cultures. To address these limitations, this thesis introduces the use of 3D bioprinting, a technology that enables the creation of three-dimensional structures capable of better representing the complexity of the tumor microenvironment. Extrusion-based bioprinting involves the precise deposition of bioinks made up of biomaterials and cells; using this technique, a three-dimensional structure was created to reproduce a multilayer compartmentalization, with the aim of studying the biological mechanisms occurring in the TME. The 3D structure was designed to represent an internal environment corresponding to the solid tumor, surrounded by an external compartment simulating the stromal tissue. Once the structure has been designed, a detailed analysis of the materials to be used was conducted, selecting biomaterials that best supported cell viability while also meeting the printability requirements. Furthermore, different cell concentrations were evaluated to optimize experimental conditions. The bioprinted constructs were then monitored over time to evaluate tumor proliferation and interactions at the interface between compartments. This work highlights the potential of 3D bioprinting in tissue engineering and cancer research, providing a versatile platform for the development of in vitro tumor models that can accelerate the discovery of new therapeutic approaches and enhance the understanding of complex interactions within the TME.