Biomimetic Vascular Grafts with Circumferentially and Axially Oriented Microporous Structures for Native Blood Vessel Regeneration

Porous grafts facilitate constructive remodeling of blood vessels. Incorporating multiple biomimetic cues to porous grafts can promote vascular regeneration. However, the fabrication of such medical devices remains challenging. Here, beta-sheet rich silk nanofibers (BSN) are added to poly(vinyl alcohol) (PVA) solution and aggregated under a cylindric electric field to form circumferentially and axially oriented tubular structures, to simulate the endothelial and media layers of blood vessels. PVA in the aligned tubes is then crystallized through repeat freezing-thawing process to offer mechanical performances. Through tuning the ratio of BSN and PVA, the composite tubes with dual anisotropic microstructures exhibit better mechanical properties than pure PVA vascular grafts. Significantly improved cell adhesion, spreading, proliferation, and alignment are achieved. Both endothelial and smooth muscle cells show improved biological activity on the grafts due to the regulatory roles of the aligned structures. In vivo studies reveal the formation of endothelial layers within four weeks of implantation, ensuring long-term patency. The endothelial and smooth muscle double layers are regenerated after eight months postimplantation, forming hierarchical microstructures and compositions similar to native vessels. The porous composite grafts with multiple aligned structures guide vascular remodeling to regenerate blood vessels, demonstrating potential for clinical translation. Vascular grafts with circumferentially and axially oriented structures are fabricated to achieve the simulation of endothelial and medial layers of blood vessels. The spatio-anisotropic features of the different layers improve biofunctions of both endothelial and smooth muscle cells, inducing vessel regeneration similar to native blood vessels. The new fabrication strategy provides bioactive composite grafts with complex biomimetic features.image