Fabrication of Perfusable Pseudo Blood Vessels by Controlling Sol-Gel Transition of Gellan Gum Templates

Construction of three-dimensional (3D) tissues with perfusable vascular networks remains a major challenge in the field of tissue engineering. Although various sacrificial templates have been employed to fabricate the vascular networks, there are some issues with respect to cytocompatibility, structural controllability, and degradability for the achievement of precisely controlled vasculatures without cytotoxicity. Here, we demonstrate a naturally occurring polysaccharide, gellan gum (GG), as a sacrificial template material due to its unique character. GG showed rapid gelation at 30-50 degrees C during the cooling process depending on the concentration of bivalent calcium ions by intermolecular ionic cross-linking and subsequent double-helix formation of GG molecules. Although chelate agents such as EDTA are generally effective in decomposing ionic cross-linking gels, e.g., alginate gel, they usually show cytotoxicity. In the case of GG gel, the gels could not be decomposed by the chelate agents but were easily decomposed by Tris-HCl buffer (pH = 7.4), which is a basic molecule with high cytocompatibility. We finally fabricated straight vascular tubes in 3D-gelatin gels and then demonstrated perfusion of human whole blood at 3.0 cm/s for 2 h. Since the complex vascular networks were constructed by 3D inkjet printing of the GG solution, GG would be useful as a structurally controllable and easily decomposable sacrificial material with cytocompatibility.