Generation of vascularized brain organoids: Technology, applications, and prospects

Abstract

Brain organoids have become important tools for studying neural development and disease modeling by closely mimicking in vivo brain architecture and function. However, despite their potential, conventional brain organoids lack a vascular system, limiting their physiological relevance and growth due to restricted oxygen and nutrient supply. Recent advances in generating vascularized brain organoids (V-Organoids) have sought to overcome such limitations, allowing for more accurate modeling of human brain development, neurovascular interactions, and blood- brain barrier (BBB) function. This article provides a comprehensive review of the methodologies employed to enhance the vascularization of brain organoids, including induction techniques, biomaterials, advanced bioengineering approaches, and in vivo implantation. The introduction of functional vasculature into brain organoids has not only enhanced their survival and maturation but also expanded their utility in disease modeling, drug screening, and regenerative medicine. We also discuss the applications of V-Organoids in the study of neurodevelopmental processes, BBB permeability in neurological disorders, brain cancer, and regeneration applications. Despite significant progress made in the development of V-Organoids, challenges such as vascular maturity, immune integration, longevity, and ethical considerations must be addressed to enable more accurate brain models, which could enhance our understanding of neurodevelopment and potential treatments.

Keywords

Vascularized brain organoids / Neurovascular interactions / Blood-brain barrier / Neurological disorders / Regeneration

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