Glucose-sensitive self-healing hydrogel as sacrificial materials to fabricate vascularized constructs

[[abstract]]A major challenge in tissue engineering is the lack of proper vascularization. Although various approaches have been used to build vascular network in a tissue engineering construct, there remain some drawbacks. Herein, a glucose-sensitive self-healing hydrogel are employed as sacrificial materials to fabricate branched tubular channels within a construct. The hydrogel composes of mainly reversibly crosslinked poly(ethylene glycol) diacrylate and dithiothreitol with borax as the glucose-sensitive motif. The hydrogel is injectable and mechanically strong after injection. Moreover, it can be rapidly removed by immersion in the cell culture medium. To show the feasibility in building a vascularized tissue construct, the designed branching vascular patterns of the glucose-sensitive hydrogel are extruded and embedded in a non glucose-sensitive hydrogel containing neural stem cells. Vascular endothelial cells seeded in the lumen of the channels by perfusion can line the channel wall and migrate into the non-sacrificial hydrogel after 3 days. In long-term ( approximately 14 days), the endothelial cells form capillary-like structure (vascular network) while neural stem cells form neurosphere-like structure (neural development) in the construct, revealing the morphology of "a vascularized neural tissue". The novel sacrificial materials can create complicated but easily removable structure for building a vascularized tissue construct particularly a neurovascular unit