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

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.

Keywords: Angiogenesis; Biomaterial; Microfluidic; Porous membranes; Vasculogenesis; ePTFE.