Nanofiber-reinforced ECM-based bioink for hybrid biofabrication of adventitia-mimetic anisotropic vascular constructs

BACKGROUND: Tissue-engineered blood vessels are essential for vascular grafting. Despite significant progress, current research predominantly focuses on the macroscopic scale of vascular grafts, neglecting the anisotropic microstructure of the vascular wall, particularly the adventitia, which plays a key role in the mechanical stability and functional performance of native vessels. Consequently, this aspect remains underexplored in current vascular tissue engineering strategies, limiting the full potential of vascular graft development. METHODS: In this study, we developed a novel hybrid biofabrication strategy combining electrospinning and coaxial extrusion printing with nanofiber-reinforced bioinks to fabricate vascular constructs that mimic the anisotropic structure of the vessel wall. The bioink, composed of a gelatin methacryloyl hydrogel matrix, contains short electrospun polycaprolactone fibers and vascular-derived extracellular matrix, which improve the mechanical stability, printability, and biocompatibility of the bioink while also providing micro/nano-scale structure. RESULTS: Using coaxial extrusion printing, we successfully fabricated vascular constructs with well-aligned fibers and cells oriented along the long axis of the artificial vessel, mimicking the micro-/nano-architecture of the adventitia. Finite element analysis revealed that shear stress during extrusion induced fiber and cell alignment, creating anisotropic structures that enhance the potential for vascular tissue engineering applications. In vivo studies demonstrated that these constructs promote host integration and vascular ingrowth without causing excessive inflammation. CONCLUSIONS: A promising strategy for fabricating vascular grafts with biomimetic adventitia-like structures is presented in this study, thereby providing a versatile platform for engineering vascular and other anisotropic tissues.