3D bioprinted gelatin/gellan gum-based scaffold with double-crosslinking network for vascularized bone regeneration.

Three-dimensional (3D) bioprinting holds promise for precise repair of bone defects, but rapid formation of effective vascularized tissue by 3D-printed construct is still a challenge. In this study, deferoxamine (DFO)-loaded ethosomes (Eth) were combined with gelatin methacrylate (GelMA)/gellan gum methacrylate (GGMA) hybrid bioink to fabricate 3D-printed scaffold by photo- and ion-crosslinking. The GelMA/GGMA bioinks showed excellent printability and improved mechanical property through the double-crosslinking method. In vitro experiments showed that Eth-DFO@GelMA/GGMA scaffold had good cytocompatibility while achieved sustained release of DFO, which significantly promoted endothelial cells migration and tube formation, mineralized matrix deposition and alkaline phosphatase expression of osteoblast. In vivo experiments of rat cranial defect model demonstrated that composite scaffold could promote angiogenesis and bone regeneration by activating the hypoxia-inducible factor 1-α (HIF1-α) signaling pathway. In conclusion, this 3D bioprinted Eth-DFO@GelMA/GGMA scaffold can couple angiogenesis and osteogenesis, and will be a promising candidate for the bone defects treatment.