Bioengineering Vascular Networks to Study Angiogenesis and Vascularization of Physiologically Relevant Tissue Models in Vitro

[Image: see text] Angiogenesis assays are essential for studying aspects of neovascularization and angiogenesis and investigating drugs that stimulate or inhibit angiogenesis. To date, there are several in vitro and in vivo angiogenesis assays that are used for studying different aspects of angiogenesis. Although in vivo assays are the most representative of native angiogenesis, they raise ethical questions, require considerable technical skills, and are expensive. In vitro assays are inexpensive and easier to perform, but the majority of them are only two-dimensional cell monolayers which lack the physiological relevance of three-dimensional structures. Thus, it is important to look for alternative platforms to study angiogenesis under more physiologically relevant conditions in vitro. Accordingly, in this study, we developed polymeric vascular networks to be used to study angiogenesis and vascularization of a 3D human skin model in vitro. Our results showed that this platform allowed the study of more than one aspect of angiogenesis, endothelial migration and tube formation, in vitro when combined with Matrigel. We successfully reconstructed a human skin model, as a representative of a physiologically relevant and complex structure, and assessed the suitability of the developed in vitro platform for studying endothelialization of the tissue-engineered skin model.