Tissue-engineered small-diameter vascular grafts containing novel copper-doped bioactive glass biomaterials to promote angiogenic activity and endothelial regeneration

Abstract

Small-diameter vascular grafts frequently fail because of obstruction and infection. Despite the wide range of commercially available vascular grafts, the anatomical uniqueness of defect sites demands patient-specific designs. This study aims to increase the success rate of implantation by fabricating bilayer vascular grafts containing bioactive glasses (BGs) and modifying their composition by removing hemostatic ions to make them blood-compatible and to enhance their antibacterial and angiogenesis properties. The porous vascular graft tubes were 3D printed using polycaprolactone, polyglycerol sebacate, and the modified BGs. The polycaprolactone sheath was then wrapped around the 3D-printed layer using the electrospinning technique to prevent blood leakage. The results demonstrated that the incorporation of modified BGs into the polymeric matrix not only improved the mechanical properties of the vascular graft but also significantly enhanced its antibacterial activity against both gram-negative and gram-positive strains. In addition, no hemolysis or platelet activity was detected after incorporating modified BGs into the vascular grafts. Copper-releasing vascular grafts significantly enhanced endothelial cell proliferation, motility, and VEGF secretion. Additionally, In vivo angiogenesis (CD31 immunofluorescent staining) and gene expression experiments showed that copper-releasing vascular grafts considerably promoted the formation of new blood vessels, low-grade inflammation (decreased expression of IL-1β and TNF-α), and high-level angiogenesis (increased expression of angiogenic growth factors including VEGF, PDGF-BB, and HEBGF). These observations indicate that the use of BGs with suitable compositional modifications in vascular grafts may promote the clinical success of patient-specific vascular prostheses by accelerating tissue regeneration without any coagulation problems.

Keywords

• Vascular grafts
• Bioactive glass
• 3D-printing
• Electrospinning
• Endothelium regeneration
• Angiogenesis