Engineered 3D-printed poly(vinyl alcohol) vascular grafts: Impact of thermal treatment and functionalization

Abstract

Cardiovascular diseases, a leading cause of global mortality, are driving increased demand for artificial blood vessels for surgical repair. This study discloses the fabrication of three-dimensional (3D)-printed small blood vessels as tissue-engineered grafts. Large-diameter artery and vein grafts are readily available in the market, but small-diameter blood vessels face issues due to the lack of suitable materials. Lysine-biofunctionalized and unmodified poly(vinyl alcohol) grafts (PVA grafts) (2 mm inner diameter and 3 mm outer diameter) suitable for veins and venules were designed using Fusion 360 software, Autodesk Fusion. The PVA channels were fabricated from the 3D virtual model through fused deposition modeling using a PVA filament. These channels underwent thermal treatment to adjust their crystallinity, chemical crosslinking, and functionalization to optimize their mechanical properties and biocompatibility. Crosslinking and biofunctionalization were assessed using Fourier-transform infrared spectroscopy with attenuated total reflectance, while X-ray diffraction and differential scanning calorimetry were utilized for structural analysis. PVA grafts were biologically tested using three specific types of cell cultures: bEnd.3 brain endothelial cells, L929 fibroblast cells, and U937 monocyte-like cells. The hemocompatibility of the optimized vascular grafts was evaluated using horse blood, following the guidelines outlined in ASTM F756-13 Standard Practice for Assessment of Hemolytic Properties of Materials. The direct method for hemoglobin determination was specifically employed. Additionally, we developed an external polyethylene terephthalate glycol (PETG) 3D-printed platform to house the PVA grafts in parallel. The assembled platform (PETG and PVA graft) was connected to both an inlet and an outlet to facilitate the passage of an aqueous flow through the internal section of the PVA grafts during a flow test conducted under simulated body conditions (vacuum and blood pressure: 40 mbar). The flow was induced by a vacuum pump connected to the outlet of the platform, while the inlet was connected to a feeding glass. In summation, we have established a suitable protocol for producing small vascular grafts and demonstrated that the optimization process could significantly affect graft properties.