From biofabrication to multi-organ platforms: engineering the human heart-kidney axis in vitro

This thesis presents an integrated in vitro approach to model the human heart–kidney axis, addressing a significant gap in understanding inter-organ communication relevant to cardiorenal syndrome (CRS). Human induced pluripotent stem cell (hiPSC)-derived organoids were used to create both cardiac microtissues and kidney organoids, enabling physiologically relevant and patient-specific experimentation. A microfluidic organ-on-chip platform was engineered to co-culture these tissues under static and perfused conditions, preserving structural and functional characteristics and allowing dynamic heart–kidney crosstalk to be investigated. Parallel work introduced a cost-effective bioprinting strategy to generate kidney organoids with improved reproducibility and scalability, overcoming limitations of manual fabrication and facilitating broader adoption of these models in biomedical research. The model enabled study of renal injury-induced cardiac dysfunction, revealing that nephrotoxic stress in kidney organoids triggered molecular and functional impairment in cardiac microtissues, consistent with CRS type 3 mechanisms. Together, these innovations demonstrate how combining stem cell technology, microfluidics, and biofabrication can recreate complex inter-organ physiology and support mechanistic insights into disease. The work highlights the translational potential of scalable, human-relevant multi-organ systems for drug screening, mechanistic studies, and future personalized medicine strategies.