3D High Throughput Bioprinted Vascularized Tissue Platform to Study Environmental Toxicant-Induced Angiogenesis and Vascular Dysfunction

Authors

• M Rajput
• MJ Song
• D kuo
• D Gerhold
• M Ferrer
• E Lee

Abstract

Environmental toxicants present a significant public health concern and are known to be a causative agent for vascular diseases. However, the full impact and profiling of environmental toxicants remain understudied. To understand the link between environmental toxins and their contribution to vascular disease, it is necessary to evaluate toxin-induced vascular dysfunction in a physiologically relevant human-based model. A 3D in vitro tissue engineering approach offers opportunities to study vascular dysfunction in a pathologically mimicked environment. Here, we developed a 96-well format, human 3D bioprinted vascularized bed platform (h3DVas) for toxicant evaluation by co-culturing primary human endothelial cells, fibroblasts, and pericytes. We then exposed the h3DVas model to a select panel of known environmental toxicants to measure vascular dysfunction. Using these environmental toxicant panels, we observed toxicant-dependent vascular damage by high-content imaging and quantified morphometric parameters. Furthermore, we measured cell viability and inflammatory response following titration of toxicant exposure by measuring intracellular ATP levels and secreted cytokines via Luminex assay, respectively. We observed vascular damage under selective environmental toxicants (Sodium Arsenite, Raloxifene HCL, Pazopanib, and Axitinib). These findings were supported by changes in quantified morphometric parameters, decreased dose-dependent cell viability, and increased levels of select inflammatory cytokines. These findings indicated vascular inflammation and vascular damage after toxicant exposure. This data suggests that the bioprinted model can be used as a potential platform to evaluate the biological activity of environmental/chemical toxicants and their health hazard.

Scientific Focus Area: Biomedical Engineering and Biophysics

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