血脑屏障（BBB）阻碍了药物向中枢神经系统的有效输送，导致脑部疾病仍然是最需要治疗的医学需求之一。了解BBB的三维结构有助于深入了解BBB的病理学，并有助于为脑部疾病开发新疗法。因此，正在开发越来越复杂的三维模型来密切模仿人类神经血管单元。在这些三维模型中，已经开发了基于水凝胶、球体和器官样的静态BBB模型，以及基于微流控的BBB芯片模型。本文回顾了BBB在健康状况和疾病状况下的不同三维临床模型的开发，从其开发到应用于渗透性测试纳米医药跨越BBB，讨论了每个模型的优缺点。对于提供在体临床数据的那些情况，也讨论了其验证。版权所有© 2023作者。由Elsevier B.V.出版。保留所有权利。

The blood-brain barrier (BBB) prevents efficient drug delivery to the central nervous system. As a result, brain diseases remain one of the greatest unmet medical needs. Understanding the tridimensional structure of the BBB helps gain insight into the pathology of the BBB and contributes to the development of novel therapies for brain diseases. Therefore, 3D models with an ever-growing sophisticated complexity are being developed to closely mimic the human neurovascular unit. Among these 3D models, hydrogel-, spheroid- and organoid-based static BBB models have been developed, and so have microfluidic-based BBB-on-a-chip models. The different 3D preclinical models of the BBB, both in health and disease, are here reviewed, from their development to their application for permeability testing of nanomedicines across the BBB, discussing the advantages and disadvantages of each model. The validation with data from in vivo preclinical data is also discussed in those cases where provided.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.