Small-Diameter Blood Vessel Substitutes: Biomimetic Approaches to Improve Patency.

Small-dimeter blood vessels (<6 mm) are required in coronary bypass and peripheral bypass surgery to circumvent blocked arteries. However, they have poor patency rates due to thrombus formation, intimal hyperplasia at the distal anastomosis, and compliance mismatch between the native artery and the graft. This review covers the state-of-the-art technologies for improving graft patency with a focus on reducing compliance mismatch between the prosthesis and the native artery. The focus of this article is on biomimetic design strategies to match the compliance over a wide pressure range.

Matching Static and Dynamic Compliance of Small-Diameter Arteries, with Poly(lactide-co-caprolactone) Copolymers: In Vitro and In Vivo Studies.

Mechanical mismatch between vascular grafts and blood vessels is a major cause of smaller diameter vascular graft failure. To minimize this mismatch, several poly-l-lactide-co-ε-caprolactone (PLC) copolymers are evaluated as candidate materials to fabricate a small diameter graft. Using these materials, tubular prostheses of 4 mm inner diameter are fabricated by dip-coating. In vitro static and dynamic compliance tests are conducted, using custom-built apparatus featuring a closed flow system with water at 37 °C. Grafts of PLC monomer ratio of 50:50 are the most compliant (1.56% ± 0.31∙mm Hg-2 ), close to that of porcine aortic branch arteries (1.56% ± 0.43∙mm Hg-2 ), but underwent high continuous dilatation (87 µm min-1 ). Better matching is achieved by optimizing the thickness of a tubular conduit made from 70:30 PLC grafts. In vivo implantation and function of a PLC 70:30 conduit of 150 µm wall-thickness (WT) are tested as a rabbit aorta bypass. An implanted 150 µm WT PLC 70:30 prosthesis is observed over 3 h. The recorded angiogram shows continuous blood flow, no aneurysmal dilatation, leaks, or acute thrombosis during the in vivo test, indicating the potential for clinical applications.

Bioprinted gelatin hydrogel platform promotes smooth muscle cell contractile phenotype maintenance.

Three dimensional (3D) bioprinting has been proposed as a method for fabricating tissue engineered small diameter vascular prostheses. This technique not only involves constructing the structural features to obtain a desired pattern but the morphology of the pattern may also be used to influence the behavior of seeded cells. Herein, we 3D bioprinted a gelatin hydrogel microchannel construct to promote and preserve the contractile phenotype of vascular smooth muscle cells (vSMCs), which is crucial for vasoresponsiveness. The microchanneled surface of a gelatin hydrogel facilitated vSMC attachment and an elongated alignment along the microchannel direction. The cells displayed distinct F-actin anisotropy in the direction of the channel. The vSMC contractile phenotype was confirmed by the positive detection of contractile marker gene proteins (α-smooth muscle actin (α-SMA) and smooth muscle-myosin heavy chain (SM-MHC)). Having demonstrated the effectiveness of the hydrogel channels bioprinted on a film, the bioprinting was applied radially to the surface of a 3D tubular construct by integrating a rotating mandrel into the 3D bioprinter. The hydrogel microchannels printed on the 3D tubular vascular construct also orientated the vSMCs and strongly promoted the contractile phenotype. Together, our study demonstrated that microchannels bioprinted using a transglutaminase crosslinked gelatin hydrogel, could successfully promote and preserve vSMC contractile phenotype. Furthermore, the hydrogel bioink could be retained on the surface of a rotating polymer tube to print radial cell guiding channels onto a vascular graft construct.