The growth of a vascular network inside a collagen–citric acid derivative hydrogel in rats

Three-dimensional regenerative tissue with a certain bulk cannot survive without sufficient blood perfusion in vivo, so construction of a vascular system in regenerative tissue is a key technology in tissue engineering. In order to construct such a vascular system, we attempted to create a scaffold material that induces neovascular growth from the recipient bed into the material. This material, an ion complex gel matrix (IC gel) consisting of collagen and a citric acid derivative, enabled it to associate with basic fibroblast growth factor (bFGF). The IC gel was implanted in the subfascial space of the rat rectus muscle and excised 5 days later. Cross-sections of the excised samples were stained for von Willebrand factor, and then neovascular development into the gel was observed and also quantified by image analysis. These data showed that the IC gel markedly induced growth of vascular-rich tissue into the inside of the gel by day 5, which surpassed that after implantation of Matrigel® or gelated collagen. Further, combination with bFGF significantly enhanced the vascularization ability of IC gel. These findings suggest that IC gel functioned as a scaffold material for neovascular ingrowth and a reservoir of bFGF.