Advanced Biofabrication of Vascularized Tissue Models under Dynamic Culture for Multi-Organ and Tumor Applications

The increasing demand for physiologically relevant and ethically sustainable in vitro models has driven significant advancements in the field of tissue engineering and biofabrication. Over the last three decades, scientific interest in this area has grown exponentially: global publications in tissue engineering have surged from a few dozen per year in the early 1990s to over 3000–4000 articles annually in recent years, marking a transition from an emerging to a consolidated research domain. This expansion reflects the strategic relevance of tissue-engineered platforms for biomedical, pharmaceutical, and cosmetic applications. This Thesis presents an integrated framework for the design, fabrication, and validation of vascularized tissue models under dynamic culture, combining hydrogel engineering, extrusion-based 3D bioprinting, and perfusable multi-tissue platforms. The overarching goal is to replicate the complexity of human tissues and their interactions in a reproducible and scalable format. The first part of the work focuses on the synthesis and comprehensive characterization of gelatin methacryloyl (GelMA)-based hydrogels, including composite formulations with Pluronic F-127. Physicochemical and mechanical properties were systematically evaluated to identify optimal compositions for biofabrication. Subsequently, the printing process was optimized using a commercial bioprinter (CELLINK BioX), with emphasis on parameter reproducibility, printability, and biocompatibility. These bioinks were used to fabricate complex tissue constructs, including vascularized models of neuroblastoma and skin, which were validated for perfusion capacity, endothelialization, and functional tissue organization. A novel fluidically connected multi-tissue platform was then developed to model early-stage melanoma metastasis. By coupling engineered skin and melanoma constructs under perfusion, the platform enabled investigation of extracellular vesicle (EV)-driven stromal reprogramming in a controlled environment. Finally, the translational potential of the developed systems was demonstrated through industrial collaboration. A techno-economic analysis assessed scalability and production costs, confirming the model's potential for commercial deployment. In summary, this work contributes to advancing modular, dynamic, and biologically relevant in vitro systems for research and industrial applications in tissue engineering and disease modeling.