LAUSR

Transplantation of progenitor cells can accelerate tissue healing and regenerative processes. Nonetheless, direct cell delivery fails to support survival of transplanted cells or long-term treatment of vascular related diseases due to compromised vasculature and tissue conditions. Using injectable hydrogels that cross-link in situ, could protect cells in vivo, but their sol-gel transition is time-dependent and difficult to precisely control. Hydrogels with self-healing properties are proposed to address these limitations, yet current self-healing hydrogels lack bio-functionality, hindering the morphogenesis of delivered cells into a tissue structure. Here we establish a gelatin (Gtn)-based self-healing hydrogel cross-linked by oxidized dextran (Odex) as an injectable carrier for delivery of endothelial progenitors. The dynamic imine cross-links between Gtn and Odex confer the self-healing ability to the Gtn-l-Odex hydrogels following syringe injection. The self-healing Gtn-l-Odex not only protects the progenitors from injected shear force but it also allows controllable spatial/temporal placement of the cells. Moreover, owing to the cell-adhesive and proteolytic sites of Gtn, the Gtn-l-Odex hydrogels support complex vascular network formation from the endothelial progenitors, both in vitro and in vivo. This is the first report of injectable, self-healing hydrogels with biological properties promoting vascular morphogenesis, which holds great promise for accelerating the success of regenerative therapies.