Assembly of organotypic tissue models using narrative and structural-based tissue engineering approaches

Abstract

Tissue engineering stands at the intersection of biology, (bio)materials science, and engineering, offering unprecedented opportunities to fabricate functional tissues that replicate the complexity of their natural counterparts. This field has evolved significantly since its inception, driven by the need for better regenerative therapies, improved disease models and reliable platforms for drug testing. By mimicking the native cellular microenvironment, tissue engineering enables the development of biomimetic structures that can restore lost function, enhance our understanding of physiological processes, and accelerate biomedical innovations. Despite considerable advancements, significant challenges remain in fabrication of large, structurally complex and physiologically relevant tissues. The integration of multiple cell types, the formation of vascular networks and the precise control of both spatial organization and differentiation are critical hurdles that must be overcome to achieve clinically relevant tissue constructs. Addressing these challenges requires a multidisciplinary approach that combines state-of-the-art biofabrication techniques with an in-depth understanding of cell biology. This thesis explores innovative approaches to tissue engineering upon integrating emerging biofabrication tools and fundamental principles of mechanobiology. By leveraging ultrasound-based assembly techniques and microgel-enabled modular biofabrication, this work introduces novel methodologies to guide tissue structure and function with high precision, with the ultimate goal to enhance the scalability, reproducibility and translational potential of engineered tissues.