3D Micro‐Nano Hierarchical Constructs Enabling Transmural Ingrowth of Adventitia Improves the “Fallout endothelialization” of Vascular Grafts

Abstract Improving transmural ingrowth of adventitia is believed to promote luminal endothelialization during host remodeling of the vascular graft. However, fabricating vascular grafts with opening microstructures favoring cell ingrowth and tunable mechanical strength warranting clinical safety remains challenging. In this study, an ultrathin nanofibrous lumen stented with a highly porous tube is fabricated to acquire a harmonious balance between mechanical stability and the requisite openness for effective cell recruitment. In vitro examination reveals clinically feasible mechanical bridging of the rabbit carotid artery, such vascular graft with 3D micro‐nano hierarchical structures (3D‐MnHCs) enable fast and sufficient cell ingrowth, including transmural angiogenesis and muscular remodeling by myofibroblasts. Harnessing an integrated spatial transcriptomics approach and angiogenesis inhibition experiments, unprecedented insights revealing the positive roles of vascularized adventitia on “Fallout” endothelialization are provided. To conclude, 3D‐MnHCs offer a“concept of proof” for balancing adequate cell ingrowth and clinically applicable strength and degrading rates, therefore introducing a novel perspective for small caliber arterial regeneration.