BioMEMS and Bioinspired Microfluidic Laboratory, Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Canada; Center for BioEngineering Research and Education, University of Calgary, Calgary, Canada.
Biomedical Engineering, Department of Mechanical Engineering, Faculty of Engineering and Architecture, American University of Beirut, Beirut 1107 2020, Lebanon.
J Control Release. 2018 Mar 10;273:108-130. doi: 10.1016/j.jconrel.2018.01.024. Epub 2018 Feb 6.
The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis and transport of drugs to the brain. The conventional animal and Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems have provided fundamental functionalities of the BBB and facilitated the testing of drug delivery to the brain tissue. However, developing biomimetic and predictive BBB models capable of reasonably mimicking essential characteristics of the BBB functions is still a challenge. In addition, detailed analysis of the dynamics of drug delivery to the healthy or diseased brain requires not only biomimetic BBB tissue models but also new systems capable of monitoring the BBB microenvironment and dynamics of barrier function and delivery mechanisms. This review provides a comprehensive overview of recent advances in microengineering of BBB models with different functional complexity and mimicking capability of healthy and diseased states. It also discusses new technologies that can make the next generation of biomimetic human BBBs containing integrated biosensors for real-time monitoring the tissue microenvironment and barrier function and correlating it with the dynamics of drug delivery. Such integrated system addresses important brain drug delivery questions related to the treatment of brain diseases. We further discuss how the combination of in vitro BBB systems, computational models and nanotechnology supports for characterization of the dynamics of drug delivery to the brain.
血脑屏障（BBB）在维持脑内环境稳定和药物向脑内转运方面发挥着至关重要的作用。传统的动物和 Transwell BBB 模型以及新兴的基于微流控的 BBB-on-chip 系统提供了 BBB 的基本功能，并促进了向脑组织输送药物的测试。然而，开发能够合理模拟 BBB 功能的仿生和预测性 BBB 模型仍然是一个挑战。此外，详细分析药物向健康或患病大脑的输送动力学不仅需要仿生 BBB 组织模型，还需要新的系统来监测 BBB 微环境以及屏障功能和输送机制的动力学。
本综述全面介绍了具有不同功能复杂性和健康与患病状态模拟能力的 BBB 模型的微工程最新进展。它还讨论了新技术，可以使包含用于实时监测组织微环境和屏障功能的集成生物传感器的下一代仿生人类 BBB 成为可能，并将其与药物输送动力学相关联。这种集成系统解决了与脑疾病治疗相关的重要脑内药物输送问题。我们进一步讨论了体外 BBB 系统、计算模型和纳米技术的结合如何支持向大脑输送药物动力学的特征描述。
