Li Yunfei, Fu Bingmei M
Department of Biomedical Engineering, The City College of the City University of New York, New York, NY 10031, USA.
Cells. 2025 Mar 19;14(6):456. doi: 10.3390/cells14060456.
By utilizing polydimethylsiloxane (PDMS), collagen hydrogel, and a cell line for human cerebral microvascular endothelial cells, we produced a 3D microchannel blood-brain barrier (BBB) model under physiological flow. This 3D BBB has a circular-shaped cross-section and a diameter of ~100 μm, which can properly mimic the cerebral microvessel responsible for material exchange between the circulating blood and brain tissue. The permeability of the 3D microchannel BBB to a small molecule (sodium fluorescein with a molecular weight of 376) and that to a large molecule (Dex-70k) are the same as those of rat cerebral microvessels. This 3D BBB model can replicate the effects of a plasma protein, orosomucoid, a cytokine, vascular endothelial growth factor (VEGF), and an enzyme, heparinase III, on either rat cerebral or mesenteric microvessesels in terms of permeability and the modulation of glycocalyx (heparan sulfate). It can also replicate the adhesion of a breast cancer cell, MDA-MB-231, in rat mesenteric microvessels under no treatment or treatments with VEGF, orosomucoid, and heparinase III. Because of difficulties in accessing human cerebral microvessels, this inexpensive and easy to assemble 3D human BBB model can be applied to investigate BBB-modulating mechanisms in health and in disease and to develop therapeutic interventions targeting tumor metastasis to the brain.
通过利用聚二甲基硅氧烷（PDMS）、胶原蛋白水凝胶以及一种人脑微血管内皮细胞系，我们在生理流动条件下构建了一种三维微通道血脑屏障（BBB）模型。这种三维血脑屏障具有圆形横截面，直径约为100μm，能够恰当地模拟负责循环血液与脑组织之间物质交换的脑微血管。三维微通道血脑屏障对小分子（分子量为376的荧光素钠）和大分子（70k右旋糖酐）的通透性与大鼠脑微血管的通透性相同。这种三维血脑屏障模型在通透性和糖萼（硫酸乙酰肝素）调节方面，能够复制血浆蛋白（orosomucoid）、细胞因子（血管内皮生长因子，VEGF）以及酶（肝素酶III）对大鼠脑或肠系膜微血管的影响。它还能够复制乳腺癌细胞（MDA - MB - 231）在未处理或经VEGF、orosomucoid和肝素酶III处理的大鼠肠系膜微血管中的黏附情况。由于获取人脑微血管存在困难，这种价格低廉且易于组装的三维人体血脑屏障模型可用于研究健康和疾病状态下血脑屏障的调节机制，并开发针对肿瘤脑转移的治疗干预措施。
