Ferro Magali P, Heilshorn Sarah C, Owens Roisin M
Department of Bioelectronics, Mines Saint-Étienne, 880 route de Mimet, F-13541, Gardanne, France.
Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
Mater Sci Eng R Rep. 2020 Apr;140. doi: 10.1016/j.mser.2019.100522. Epub 2020 Jan 6.
Brain homeostasis relies on the selective permeability property of the blood brain barrier (BBB). The BBB is formed by a continuous endothelium that regulates exchange between the blood stream and the brain. This physiological barrier also creates a challenge for the treatment of neurological diseases as it prevents most blood circulating drugs from entering into the brain. cell models aim to reproduce BBB functionality and predict the passage of active compounds through the barrier. In such systems, brain microvascular endothelial cells (BMECs) are cultured in contact with various biomaterial substrates. However, BMEC interactions with these biomaterials and their impact on BBB functions are poorly described in the literature. Here we review the most common materials used to culture BMECs and discuss their potential impact on BBB integrity . We investigate the biophysical properties of these biomaterials including stiffness, porosity and material degradability. We highlight a range of synthetic and natural materials and present three categories of cell culture dimensions: cell monolayers covering non-degradable materials (2D), cell monolayers covering degradable materials (2.5D) and vascularized systems developing into degradable materials (3D).
脑稳态依赖于血脑屏障(BBB)的选择性通透特性。血脑屏障由连续的内皮细胞构成,调节着血流与脑之间的物质交换。这种生理屏障也给神经疾病的治疗带来了挑战,因为它会阻止大多数血液循环中的药物进入大脑。细胞模型旨在重现血脑屏障的功能,并预测活性化合物透过该屏障的情况。在这类系统中,脑微血管内皮细胞(BMECs)与各种生物材料底物接触培养。然而,文献中对BMECs与这些生物材料的相互作用及其对血脑屏障功能的影响描述甚少。在此,我们综述了用于培养BMECs的最常见材料,并讨论它们对血脑屏障完整性的潜在影响。我们研究了这些生物材料的生物物理特性,包括硬度、孔隙率和材料降解性。我们重点介绍了一系列合成材料和天然材料,并呈现了三类细胞培养维度:覆盖不可降解材料的细胞单层(二维)、覆盖可降解材料的细胞单层(2.5维)以及向可降解材料发展的血管化系统(三维)。