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REVIEW ARTICLE

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

Quan-Jing Mei1 ,  Jia-Qi Wen1 ,  Xiao-Xiao Xu2 ,  Hui-Qi Xie1,3*
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1 Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
2 Department of Medical Biophysics, The Temerty Faculty of Medicine, University of Toronto, Toronto, M5S 1A8, Ontario, Canada
3 Tianfu Jincheng Laboratory, Chengdu, 610093, China
OR, 8162 https://doi.org/10.36922/or.8162
Submitted: 24 December 2024 | Revised: 13 February 2025 | Accepted: 14 March 2025 | Published: 16 April 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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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
Funding
The authors sincerely appreciate the support provided by the Sichuan Science and Technology Program (2024NSFSC0002), the China Postdoctoral Science Foundation (2024M762224), the Frontiers Medical Center, Tianfu Jincheng Laboratory Foundation (TFJC2023010002), and the “1.3.5” Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYGD23037).
Conflict of interest
Hui Qi Xie is an Editorial Board Member of this journal but was not involved in any way in the editorial or peer-review process conducted for this paper, either directly or indirectly. Separately, the other authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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