Dynamic Straining Combined with Fibrin Gel Cell Seeding Improves Strength of Tissue-Engineered Small-Diameter Vascular Grafts

TLDR

Vascular tissue engineering offers a promising approach for creating living small‑diameter grafts for replacement therapy, yet achieving strong human TE grafts has historically required several months of culture, even with gene therapy. The study aims to produce strong, genetically unmodified human TE vascular grafts within four weeks using a fast‑degrading polyglycolic acid scaffold coated with poly‑4‑hydroxybutyrate, fibrin gel, and myofibroblasts isolated from discarded saphenous veins. The grafts were fabricated on the scaffold, seeded with myofibroblasts, and cultured under dynamic strain conditions for 28 days. After 28 days, the grafts achieved burst pressures of 903 ± 123 mmHg, displayed mechanical properties comparable to native LIMA up to 300 mmHg, contained about 50 % of native collagen, and thus demonstrate that dynamic conditioning with fibrin gel cell seeding markedly improves mechanical strength, offering a promising alternative to current vascular replacements.

Abstract

Vascular tissue engineering represents a promising approach for the development of living small-diameter vascular grafts that can be used for replacement therapy. The culture of strong human tissue-engineered (TE) vascular grafts has required long culture times, up to several months, whether or not combined with gene therapy. This article describes the culture of strong, genetically unmodified, human TE vascular grafts in 4 weeks Small-diameter vascular grafts were engineered using a fast-degrading polyglycolic acid scaffold coated with poly-4-hydroxybutyrate combined with fibrin gel and seeded with myofibroblasts isolated from discarded saphenous veins from patients undergoing coronary bypass surgery. The TE grafts were subjected to dynamic strain conditions. After 28 d of in vitro culture, the grafts demonstrated burst pressures of 903 +/- 123 mmHg. Comparison with native vessels (intact human left internal mammary arteries (LIMAs) and saphenous veins) showed no significant differences in the amount of DNA, whereas the TE vessels contained approximately 50% of the native collagen content. In the physiological pressure range, up to 300 mmHg, the mechanical properties of the TE vessels were comparable to the LIMA. In this study, we showed that dynamic conditioning combined with fibrin gel cell seeding enhances the mechanical properties of small-diameter TE grafts. These grafts might provide a promising alternative to currently used vascular replacements.