Angela Ruohao Wu

the Division of Life Science, the Department of Chemical and Biological Engineering, the Hong Kong University of Science and Technology, HK, China

Cerebral organoids are self-organizing 3D in vitro models widely used to study human neurodevelopment, yet they lack integrated vascular networks.  In  vivo,  the  developing  brain  is  vascularized  through mesodermal  angiogenic  sprouts,  which  support  neuron  survival,maturation,  and  migration.  As  the   brain  derives  from  ectodermal lineage,   conventional   cerebral    organoids   cannot    form   intrinsic vasculature, resulting in impaired neuronal maturation, necrotic cores, and the absence of a blood-brain barrier (BBB), limiting their use in pharmacological and drug permeability studies. Here, we present a microfluidics-assisted strategy to generate perfusable vascularized human cerebral  organoids  (pvhCOs).  By  engineering  and  guiding  endothelial  cells,  our  method establishes  connected  vascular  networks  capable  of  continuous  media  perfusion  into  the organoid core, mimicking physiological delivery. These networks remain functional for up to four months, supporting the cultivation of larger organoids and promoting advanced neuronal and glial maturation. The system provides a robust platform for chronic exposure studies—including neurodegeneration,    persistent     infection,     and    neurovascular     interactions—offering     a physiologically   relevant,   cost-effective,   and   ethical   alternative   to   animal   models   while overcoming a key limitation of conventional cerebral organoids.