Mechanically stable, endothelializable vascular graft scaffolds fabricated by melt electrowriting

Conventional synthetic vascular grafts, especially for small-diameter vessels (<6 mm), still face critical limitations in clinical settings, as around 75% of synthetic conduits fail within 3 years of implantation mostly due to the missing luminal endothelial cell layer, leading to, e.g ., thrombosis, calcification, and intimal hyperplasia. Mechanical mismatch between the graft and native tissue can lead to severe clinical complications. Thus, tissue-engineered vascular grafts have become of wide interest as they aim to overcome clinical challenges of synthetic grafts by mimicking the qualities of native tissue. Here, we developed a framework for the fabrication of a customizable, 3D-printed tubular scaffold structure consisting of poly- ε-caprolactone (PCL) with controlled mechanical properties mimicking those of native arteries. Design adjustments regarding the geometric properties of the 3D-printed scaffolds were made by varying winding angle, fiber diameter, and fiber distance. A fibrin compression molding technique was adapted to produce a leak-free and cell-adherent vascular graft structure that was later seeded with endothelial cells and cultivated under pulsatile dynamic conditions of up to 20 dyn*cm -2 . The final scaffold had a fiber diameter of 128 μm, a winding angle of 52.5°, and a fiber distance of 500 µm. Printed with long-chain PCL showed a radial Young’s modulus of 1.12 ± 0.35 MPa and a radial tensile strength of 3.89 ± 0.81 MPa, similar to that of native arteries (2.45 ± 0.79 MPa). The fibrin-PCL scaffold showed a burst pressure of 1,600.4 ± 502.85 mmHg, a suture strength of 1.62 ± 0.29 N, a longitudinal tensile strength similar to native arteries (1.07 ± 0.22 MPa), whereas radial tensile strength was decreased (0.80 ± 0.20 MPa). Finally, successful endothelialization of the fibrin PCL graft under pulsatile and dynamic cultivation (20 dyn*cm -2 ) over 7 days was demonstrated, with cell alignment according to the direction of flow. Additionally, the cultivated graft still retained sufficient biomechanical properties with a radial Young’s modulus of 3.03 MPa and a radial tensile strength of 1.56 MPa. To the best of our knowledge, this study demonstrates the successful fabrication of an endothelialized graft that possesses mechanical properties similar to those of native arteries.