Artificial Vasa-Vasorum Serves as an On-Site Regenerative Promoter of Cell-Free Vascular Grafting

The control paradigm of small vessel pathophysiology has changed to focus on the vascular out-wall rather than the lumen-intimal factors. As an emerging controller of the external wall, the microvasculature ("vasa vasorum") provides interactional routes between the in-and out-sides of the vascular wall. Despite numerous approaches to developing small-diameter vascular grafts, engineering artificial vasa vasorum (AVV) has not been projected as a multi-functional solution to address long-standing issues such as thrombotic and immune controls for wall regeneration. Here, the AVV is engineered using a microchannel network hydrogel after a multi-study validation of implantation functions and then used to wrap the external wall of the cell-free vessel post-decellularization while preserving its mechanical properties. Upon inter-positional and bypass grafting to rabbit arteries, the AVV graft facilitates the recruitment of vascular cells into the cell-free wall by promoting invasion of angiogenic and vasculogenic cells through the microchannel-mediated M2 polarization of macrophages. This function results in the efficient restoration of smooth muscle cells, and the revitalized vascular elasticity helps to maintain long-term patency. The AVV, therefore, serves as an effective catalyst for vascular wall regeneration, offering a solution to clinically successful small-diameter vascular grafting. The clinical success of small-diameter vascular grafting with long-term patency highlights artificial vasa vasorum (AVV) through outside-in control. AVV, featuring a dense microvascular network within hydrogel, promotes endothelial cell recruitment and macrophage M2 polarization, while restoring smooth muscle cells. This approach addresses thrombotic and immune control issues, providing a foundational solution for clinical small-diameter vascular grafting success. image