Development of an acino-ductal unit 3D in vitro model through additive manufacturing technologies

Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal malignancy of the exocrine pancreas, primarily due to unspecific symptoms, late diagnosis, and resistance to existing treatments. The fibrotic and heterogeneous structure of the tumor microenvironment further complicates its study, underscoring the urgent need for advanced research models. In this context, additive manufacturing techniques have been applied for the development of in vitro organ models. These models offer the advantage of replicating the geometry of physiological tissue, while simultaneously ensuring the customizability and reproducibility of the produced constructs. This study aims to develop a biomimetic 3D scaffold-based model of pancreatic tissue, focusing on replicating tissue composition and geometry. To achieve this, melt electrowriting was selected as the manufacturing technique to produce microfibrous scaffolds with highly controllable fiber deposition. The scaffold design and printing process were optimized using a Python script, developed to enhance key parameters such as the fiber disposition and the efficiency of material consumption. Finally, a cell coculture that replicates the interactions between the tumor and the stroma has been conducted, mimicking the fundamental characteristics of the tumor microenvironment. The preliminary results exhibited an efficient proliferation and a colonization of the cells within the construct. Additionally, the scaffold design proved to be particularly advantageous in facilitating confocal imaging, simplifying the analysis of cellular behavior within the construct.