用于疾病建模和药物开发的微生理血脑屏障系统。

Microphysiological Blood-Brain Barrier Systems for Disease Modeling and Drug Development.

机构信息

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

出版信息

Adv Healthc Mater. 2024 Aug;13(21):e2303180. doi: 10.1002/adhm.202303180. Epub 2024 Mar 12.

Abstract

The blood-brain barrier (BBB) is a highly controlled microenvironment that regulates the interactions between cerebral blood and brain tissue. Due to its selectivity, many therapeutics targeting various neurological disorders are not able to penetrate into brain tissue. Pre-clinical studies using animals and other in vitro platforms have not shown the ability to fully replicate the human BBB leading to the failure of a majority of therapeutics in clinical trials. However, recent innovations in vitro and ex vivo modeling called organs-on-chips have shown the potential to create more accurate disease models for improved drug development. These microfluidic platforms induce physiological stressors on cultured cells and are able to generate more physiologically accurate BBBs compared to previous in vitro models. In this review, different approaches to create BBBs-on-chips are explored alongside their application in modeling various neurological disorders and potential therapeutic efficacy. Additionally, organs-on-chips use in BBB drug delivery studies is discussed, and advances in linking brain organs-on-chips onto multiorgan platforms to mimic organ crosstalk are reviewed.

摘要

血脑屏障 (BBB) 是一个高度受控的微环境,调节着脑血液和脑组织之间的相互作用。由于其选择性,许多针对各种神经疾病的治疗药物无法穿透脑组织。使用动物和其他体外平台进行的临床前研究未能完全复制人类 BBB,导致大多数治疗药物在临床试验中失败。然而,最近体外和离体建模方面的创新——器官芯片,显示出了为改善药物开发而创建更准确疾病模型的潜力。这些微流控平台对培养细胞施加生理应激,并能够生成比以前的体外模型更具生理准确性的 BBB。在这篇综述中,探讨了创建 BBB 芯片的不同方法,以及它们在模拟各种神经疾病和潜在治疗效果方面的应用。此外,还讨论了器官芯片在 BBB 药物输送研究中的应用,并回顾了将脑器官芯片连接到多器官平台上以模拟器官串扰方面的进展。

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