Engineering a compartmentalized tumor model: an approach based on 3D bioprinting of advanced biomaterials

The purpose of the thesis project is to develop a three-dimensional (3D) model of pathological tissue through 3D printing methods, focusing mainly on the control of the fibrillar structure of collagen, fundamental component of the stromal extracellular matrix (ECM). The bioink formulation is designed to simulate the native stromal matrix using a composite hydrogel made of hyaluronic acid, of different molecular weights, and collagen type I. The morphology of the collagen fibers is precisely modulated through the variation of pre-fibrillation conditions and bioprinting parameters. Multiple tests are performed to optimize the rheological properties and stability of the bioink, as well as to obtain a robust control on the fibrillar structure. The fabrication 3D scaffolds will be approached using two different strategies: direct extrusion printing and printing with material support (FRESH, Freeform Reversible Embedding of Suspended Hydrogels). By fine-tuning printing parameters and bioinks components, three-dimensional constructs will be designed to mimic various degrees of isotropic or anisotropic orientation of collagen typical of solid tumors. The aim is to produce models that mimic structural and mechanical architectures of physiological tumor tissue, making it possible to study in vitro the influence of collagen architecture on cell behavior.