First long-term preclinical evaluation of woven vascular grafts made from human cell-assembled extracellular matrix.

Abstract

To meet the clinical need for small-diameter vascular grafts, we propose a new generation of Tissue-Engineered Vascular Grafts (TEVGs) based on the textile assembly of the Cell-Assembled extracellular Matrix (CAM): a non-cross-linked, entirely biological, and human biomaterial produced by cells in culture. Previously, we demonstrated the feasibility of producing woven CAM tubes with mechanical properties suitable for use as vascular grafts. In this study, we demonstrate, for the first time, the long-term use of these woven TEVGs in vivo. Miniaturized human TEVGs were produced, thanks to the versatility of the weaving process, and successfully implanted in the abdominal aorta of immunosuppressed rats. After one year, ultrasound images revealed flow through the TEVGs (overall patency: 86%). A neo-media was observed on the luminal surface as early as 1 month and was composed of differentiated muscular cells and elastin, covered by a monolayer of confluent and aligned endothelial cells. The immune response to TEVGs, mainly driven by M2-type macrophages, was mild and decreased over time. Unexpectedly, CAM calcification was observed in areas of high biomaterial compaction, a phenomenon never observed in previous in vivo CAM studies. This work showed that CAM-based textiles persist for at least one year in a vascular graft position. In conclusion, the woven assembly of the CAM produced a highly promising vascular graft, given its excellent in vivo stability and integration.