Cerebral cavernous malformations (CCMs) are neurovascular anomalies caused by mutations in CCM genes, disrupting brain capillary homeostasis. With no pharmacological therapies and surgery as the only curative option, there is an urgent need for humanized models to study CCM pathogenesis and identify new treatments. Current CCM models lack perfusion, a critical extrinsic factor that influences endothelial cell behaviour. This project aims to develop perfused vascular models (e.g. organoids and OoC) carrying homozygous or heterozygous CCM mutations - the latter modelling a predisposed genetic background vulnerable to environmental "second hits." The strategy includes: (1) CCM gene editing, (2) generation of vascularized models, (3) integration of physiological flow to mimic brain perfusion, and (4) use of this model to test drug candidates and environmental modulators such as hypoxia or inflammation. This platform merges genetic and tissue engineering with advanced microscopy and precision medicine, enabling mechanistic insight and therapeutic discovery in a clinically relevant context.