REVIEW article
Front. Pharmacol.
Sec. Integrative and Regenerative Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1637602
This article is part of the Research Topic3D in Vitro Models - A New Era in Cancer ResearchView all articles
3D In Vitro Blood–Brain Barrier Models: Recent Advances and Their Role in Brain Disease Research and Therapy
Provisionally accepted
- 1Limerick Digital Cancer Research Centre, School of Medicine, University of Limerick, Limerick, Ireland
- 2University of Limerick School of Medicine, Limerick, Ireland
- 3University of Limerick Health Research Institute, Limerick, Ireland
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The blood-brain barrier (BBB) is a dynamic and highly selective interface crucial to central nervous system (CNS) homeostasis, presenting a major challenge for effective drug delivery in treating CNS pathologies such as brain tumours and neurodegenerative disease. Traditional two-dimensional (2D) in vitro models and animal models often fail to replicate the structural complexity and physiological functions of the human BBB. Recent advances in three-dimensional (3D) in vitro modelling offer enhanced physiological relevance by integrating cellular architecture, extracellular matrix (ECM) components, and dynamic fluid flow to simulate in vivo conditions more accurately. This review explores the structural and functional features of the BBB and highlights the evolution from 2D to 3D in vitro models, including hydrogel-based systems, microfluidics, organ-on-a-chip (OOAC) platforms, spheroids and organoids. The advantages of these models in recapitulating BBB dynamics and their application in cancer research and other CNS diseases are discussed. Finally, critical comparison and discussion of current 3D models is presented, highlighting differences and best potential uses of each variation. Continued advancements are needed to develop accurate 3D in vitro models of the BBB in order to revolutionize drug screening, predict therapeutic efficacy, and support personalized medicine approaches. By providing robust, human-relevant platforms, 3D BBB models can accelerate drug development and treatment for patients affected by CNS pathologies.
Keywords: Blood-Brain Barrier, 3D, in vitro, Central Nervous System, brain tumour, organ-on-a-chip
Received: 06 Jun 2025; Accepted: 18 Sep 2025.
Copyright: © 2025 O'Halloran, Akinsete, Kogan, Wrona and Mahdi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Amira F Mahdi, amira.mahdi@ul.ie
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