Microscopically Adaptable Bioink Guide Cell Compartmentalization toward Morphogenesis of a Functional Vasculature-Like System.

Prevascularization is the key challenge for large-scale tissue engineering. Nevertheless, none of the engineered vasculature simultaneously recapitulates the multi-layered heterogeneous characterizations and functions yet. The recent studies reveal that matrix dynamics play an important role in vasculature morphogenesis. In this study, an extracellular matrix-mimicking bioink is developed by the interpenetrated dynamic-covalent crosslinking orthogonal design. The dynamic covalent crosslinking network of the bioink allows an adaptable microenvironment contributing to the functional compartmentalization of endothelial cells and smooth muscle cells toward histological vasculature configurations. Focal adhesion kinase pathway participates in the morphogenesis process by coupling the microscopically adaptable environment to the vasculature organization via upregulation of integrin-mediated adhesion and glycolysis. The engineered vasculature exhibits in vitro contraction in response to angiotensin II and significantly improves blood perfusion in the mouse hind limb ischemia model. In addition, the vascular network successfully prolongs the survival and function of surrounding human dermal fibroblasts postimplantation, which enhances the healing of large full-thickness wounds. Altogether, this work presents a one-step bioprinting strategy of prevascularization in predesigned architecture for vascular tissue engineering.