3D-bioprintable endothelial cell-laden sacrificial ink for fabrication of microvessel networks

Abstract

Abstract Although various research efforts have been made to produce a vascular-like network structure as scaffolds for tissue engineering, there are still several limitations. Meanwhile, no articles have been published on the direct embedding of cells within a glucose sensitive sacrificial hydrogel followed by three-dimensional (3D) bioprinting to fabricate vascular structures. In this study, the hydrogel composed of reversibly crosslinked poly(ethylene glycol) diacrylate and dithiothreitol with borax and branched polyethylenimine was used as the sacrificial hydrogel to fabricate vascular-like network structure. The component proportion ratio of the sacrificial hydrogel was optimized to achieve proper self-healing, injectable, glucose-sensitive, and 3D printing properties through the balance of boronate ester bond, hydrogen bond, and steric hinderance effect. The endothelial cells (ECs) can be directly embedded into sacrificial hydrogel and then bioprinted through a 110 μm nozzle into the neural stem cell (NSC)-laden non-sacrificial hydrogel, forming the customized EC-laden vascularized microchannel (one-step). The EC-laden sacrificial hydrogel was dissolved immediately in the medium while cells kept growing. The ECs proliferated well within the vascularized microchannel structure and were able to migrate to the non-sacrificial hydrogel in one day. ECs and NSCs interacted around the vascularized microchannel to form capillary-like structure and vascular-like structure expressing CD31 in 14 d. The sacrificial hydrogel conveniently prepared from commercially available chemicals through simple mixing can be used in 3D bioprinting to create customized and complex but easily removable vascularized structure for tissue engineering applications.