Control of vascular network location in millimeter-sized 3D-tissues by micrometer-sized collagen coated cells

Engineering three-dimensional (3D) vascularized constructs remains a central challenge because capillary network structures are important for sufficient oxygen and nutrient exchange to sustain the viability of engineered constructs. However, construction of 3D-tissues at single cell level has yet to be reported. Previously, we established a collagen coating method for fabricating a micrometer-sized collagen matrix on cell surfaces to control cell distance or cell densities inside tissues. In this study, a simple fabrication method is presented for constructing vascular networks in 3D-tissues over micrometer-sized or even millimeter-sized with controlled cell densities. From the results, well vascularized 3D network structures can be observed with a fluorescence label method mixing collagen coated cells and endothelia cells, indicating that constructed ECM rich tissues have the potential for vascularization, which opens up the possibility for various applications in pharmaceutical or tissue engineering fields.