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一种用于评估多孔膜中血管生成的新型 3D 血管分析方法。

A novel 3D vascular assay for evaluating angiogenesis across porous membranes.

机构信息

Department of Mechanical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

W. L. Gore & Associates, Inc., Flagstaff, AZ, 86004/Cambridge, MA, 02142, USA.

出版信息

Biomaterials. 2021 Jan;268:120592. doi: 10.1016/j.biomaterials.2020.120592. Epub 2020 Dec 8.

Abstract

Microfluidic technology has been extensively applied to model the functional units of human organs and tissues. Since vasculature is a key component of any functional tissue, a variety of techniques to mimic vasculature in vitro have been developed to address complex physiological and pathological processes in 3D tissues. Herein, we developed a novel, in vitro, microfluidic-based model to probe microvasculature growth into and across implanted porous membranes. Using ePTFE and polycarbonate as examples, we characterize the vascularization potential of these thin porous membranes using this device. This tool will allow for the assessment of porous materials early in their development, prior to their use for encapsulating implants or drugs, while minimizing the need for animal studies. Employing quantitative morphometric analysis and measurements of vascular permeability, we demonstrate our model to be an effective platform for evaluation of angiogenic potential of an implanted membrane biomaterial. Results show that endothelial cells can either migrate as single cells or form continuous sprouts across porous membranes, which is a material structure-dependent behavior. Our model is advantageous over conventional Transwell assays as it is amenable to quantitative assessment of vascular sprouting in 3D, and in contrast to animal models it can be employed more efficiently and with real-time assessment capabilities. This new tool could be applied either to test the suitability of a wide range of biomaterials for implantation or to screen different pro-angiogenic factors for therapeutic applications, and will advance the design of new biomaterials.

摘要

微流控技术已广泛应用于模拟人体器官和组织的功能单元。由于脉管系统是任何功能性组织的关键组成部分,因此已经开发出各种模拟体外脉管系统的技术,以解决 3D 组织中的复杂生理和病理过程。在此,我们开发了一种新颖的、基于体外微流控的模型,用于探测微血管生长到植入的多孔膜中和穿过多孔膜。使用 ePTFE 和聚碳酸酯作为示例,我们使用该装置来表征这些薄多孔膜的血管生成潜力。该工具将允许在将多孔材料用于封装植入物或药物之前对其进行早期评估,从而最大限度地减少对动物研究的需求。通过定量形态计量分析和血管通透性测量,我们证明了我们的模型是评估植入膜生物材料血管生成潜力的有效平台。结果表明,内皮细胞可以作为单个细胞迁移或穿过多孔膜形成连续的芽,这是一种依赖于材料结构的行为。与传统的 Transwell 测定相比,我们的模型具有优势,因为它适用于对 3D 中的血管生成芽进行定量评估,与动物模型相比,它可以更有效地进行评估,并且具有实时评估能力。这种新工具可以用于测试广泛的生物材料是否适合植入,或者筛选不同的促血管生成因子用于治疗应用,从而推进新型生物材料的设计。

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