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用于模拟血脑屏障的微流控系统:从市场到工程挑战与展望

Microfluidic Systems to Mimic the Blood-Brain Barrier: from Market to Engineering Challenges and Perspectives.

作者信息

da Silva Gabriela Gomes, Sacomani Daniel Pereira, de Carvalho Bruna Gregatti, Porcionatto Marimélia Aparecida, Gobbi Angelo, Lima Renato Sousa, de la Torre Lucimara Gaziola

机构信息

Department of Material and Bioprocess Engineering, School of Chemical Engineering, University of Campinas (UNICAMP), Campinas, São Paulo 13083-970, Brazil.

National Institute of Science and Technology in Modeling Human Complex Diseases with 3D Platforms (INCT Model3D), São Paulo, São Paulo 04039-032, Brazil.

出版信息

ACS Biomater Sci Eng. 2025 Jun 25. doi: 10.1021/acsbiomaterials.4c02221.


DOI:10.1021/acsbiomaterials.4c02221
PMID:40560145
Abstract

Studying and understanding complex biological systems is a challenge that requires technologies that go beyond traditional cell culture methods. Among the new technologies that have been developed in recent times, blood-brain barrier-on-a-chip (BBB-on-a-chip) models are becoming popular. Due to their ability to integrate fluid flow, which is absent in traditional static models, it has been possible to create a cellular microenvironment that mimics blood vessels and blood flow. In addition, the possibility of coculturing different cell types in multicellular models allows the observation of their interactions and increases interest in these systems. With different possibilities in terms of prototyping techniques (e.g., laminate manufacturing, molding, and 3D impression), chip designs (e.g., planar and cylindrical configurations), and materials (e.g., thermoplastics, elastomers, and hydrogels), the number of publications in the BBB research field has significantly increased in the last five years. In parallel, the emergence and consolidation of several companies have made the commercialization and application of these chips possible, mainly in the pharmaceutical area, which is not yet integrated into the drug development pipeline. In this context, the present review describes the intersection between technique, market, and applications that mimic the BBB. We showed organ-on-a-chip (OoC) market growth and the collaborative research between the main OoC supplier companies and industrial collaborators. Also, we present an overview of the primary fabrication methods used in constructing the OoC systems and their application in developing the BBB models. In addition, we discussed the BBB-on-a-chip designs developed in the last five years, including their engineering aspects (such as materials, dimensions, and configuration), characterization, and challenges in mimicking the BBB.

摘要

研究和理解复杂的生物系统是一项挑战,需要超越传统细胞培养方法的技术。在近年来开发的新技术中,芯片上的血脑屏障(BBB芯片)模型正变得越来越流行。由于它们能够整合流体流动,而这在传统的静态模型中是不存在的,因此有可能创建一个模拟血管和血流的细胞微环境。此外,在多细胞模型中共培养不同细胞类型的可能性使得能够观察它们之间的相互作用,并增加了人们对这些系统的兴趣。由于在原型制作技术(例如层压制造、模塑和3D打印)、芯片设计(例如平面和圆柱形配置)以及材料(例如热塑性塑料、弹性体和水凝胶)方面有不同的可能性,在过去五年中,BBB研究领域的出版物数量显著增加。与此同时,几家公司的出现和巩固使得这些芯片的商业化和应用成为可能,主要是在制药领域,而该领域尚未纳入药物开发流程。在这种背景下,本综述描述了模拟BBB的技术、市场和应用之间的交叉点。我们展示了芯片上器官(OoC)市场的增长以及主要OoC供应商公司与行业合作伙伴之间的合作研究。此外,我们概述了构建OoC系统所使用的主要制造方法及其在开发BBB模型中的应用。此外,我们讨论了过去五年中开发的BBB芯片设计,包括它们的工程方面(如材料、尺寸和配置)、表征以及在模拟BBB方面的挑战。

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本文引用的文献

[1]
Organoids meet microfluidics: recent advancements, challenges, and future of organoids-on-chip.

In Vitro Model. 2025-3-5

[2]
A Human Brain-Chip for Modeling Brain Pathologies and Screening Blood-Brain Barrier Crossing Therapeutic Strategies.

Pharmaceutics. 2024-10-10

[3]
Real-time monitoring of a 3D blood-brain barrier model maturation and integrity with a sensorized microfluidic device.

Lab Chip. 2024-11-5

[4]
Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction.

Biomaterials. 2025-3

[5]
Brain-on-a-chip: an emerging platform for studying the nanotechnology-biology interface for neurodegenerative disorders.

J Nanobiotechnology. 2024-9-18

[6]
Assessing Drug Uptake and Response Differences in 2D and 3D Cellular Environments Using Stimulated Raman Scattering Microscopy.

Anal Chem. 2024-9-10

[7]
Effects of Amyloid Beta (Aβ) Oligomers on Blood-Brain Barrier Using a 3D Microfluidic Vasculature-on-a-Chip Model.

Appl Sci (Basel). 2024-5-1

[8]
Development of a 3D printed perfusable blood-brain barrier model for use as a scalable screening tool.

Biomater Sci. 2024-8-20

[9]
Modeling of Blood-Brain Barrier (BBB) Dysfunction and Immune Cell Migration Using Human BBB-on-a-Chip for Drug Discovery Research.

Int J Mol Sci. 2024-6-12

[10]
Functional Integration of Synthetic Cells into 3D Microfluidic Devices for Artificial Organ-On-Chip Technologies.

Adv Healthc Mater. 2024-9

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