Royse Madison K, Means A Kristen, Calderon Gisele A, Kinstlinger Ian S, He Yufang, Durante Marc R, Procopio Adam T, Veiseh Omid, Xu Jun
Department of Bioengineering, Rice University, 6100 Main St., Houston, TX 77005, USA.
Division of Technology, Infrastructure, Operations & Experience, Merck & Co., Inc., Rahway, NJ 07065, USA.
Biomater Sci. 2022 Jun 14;10(12):3158-3173. doi: 10.1039/d2bm00223j.
The development of an model to study vascular permeability is vital for clinical applications such as the targeted delivery of therapeutics. This work demonstrates the use of a perfusion-based 3D printable hydrogel vascular model as an assessment for endothelial permeability and its barrier function. Aside from providing a platform that more closely mimics the dynamic vascular conditions , this model enables the real-time observation of changes in the endothelial monolayer during the application of ultrasound to investigate the downstream effect of ultrasound-induced permeability. We show an increase in the apparent permeability coefficient of a fluorescently labeled tracer molecule after ultrasound treatment a custom MATLAB algorithm, which implemented advanced features such as edge detection and a dynamic region of interest, thus supporting the use of ultrasound as a non-invasive method to enhance vascular permeability for targeted drug therapies. Notably, live-cell imaging with VE-cadherin-GFP HUVECs provides some of the first real-time acquisitions of the dynamics of endothelial cell-cell junctions under the application of ultrasound in a 3D perfusable model. This model demonstrates potential as a new scalable platform to investigate ultrasound-assisted delivery of therapeutics across a cellular barrier that more accurately mimics the physiologic matrix and fluid dynamics.
开发用于研究血管通透性的模型对于诸如治疗药物的靶向递送等临床应用至关重要。这项工作展示了基于灌注的3D可打印水凝胶血管模型作为评估内皮通透性及其屏障功能的用途。除了提供一个更紧密模拟动态血管条件的平台外，该模型还能够在应用超声期间实时观察内皮单层的变化，以研究超声诱导的通透性的下游效应。我们展示了在超声处理后，使用自定义MATLAB算法，荧光标记示踪分子的表观渗透系数增加，该算法实现了诸如边缘检测和动态感兴趣区域等高级功能，从而支持将超声作为一种非侵入性方法来增强血管通透性以用于靶向药物治疗。值得注意的是，使用VE-钙黏蛋白-GFP人脐静脉内皮细胞进行活细胞成像，首次在3D可灌注模型中实时获取了超声作用下内皮细胞间连接的动态变化。该模型展示了作为一个新的可扩展平台的潜力，用于研究超声辅助治疗药物跨细胞屏障的递送，该平台更准确地模拟了生理基质和流体动力学。
