Engineering tissues with a perfusable vessel-like network using endothelialized alginate hydrogel fiber and spheroid-enclosing microcapsules

Development of the technique for constructing an internal perfusable vascular network is a challenging issue in fabrication of dense three-dimensional tissues in vitro. Here, we report a method for realizing it. We assembled small tissue (about 200 μm in diameter)-enclosing hydrogel microcapsules and a single hydrogel fiber, both covered with human vascular endothelial cells in a collagen gel. The microcapsules and fiber were made from alginate and gelatin derivatives, and had cell adhesive surfaces. The endothelial cells on the hydrogel constructs sprouted and spontaneously formed a network connecting the hydrogel constructs with each other in the collagen gel. Perfusable vascular network-like structure formation after degrading the alginate-based hydrogel constructs by alginate lyase was confirmed by introducing solution containing tracer particles of about 3 μm in diameter into the lumen templated by the alginate hydrogel fiber. The introduced solution flowed into the spontaneously formed capillary branches and passed around the individual spherical tissues.