Regional Differences in Vascular Graft Degradation and Regeneration Contribute to Dilation.

Abstract

Severe coronary artery disease is often treated with a coronary artery bypass graft using an autologous blood vessel. When this is not available, a commercially available synthetic graft can be used as an alternative but is associated with high failure rates and complications. Therefore, the research focus has shifted toward the development of biodegradable, regenerative vascular grafts that can convert into neoarteries. We previously developed an electrospun tropoelastin (TE)-polyglycerol sebacate (PGS) vascular graft that rapidly regenerated into a neoartery, with a cellular composition and extracellular matrix approximating the native aorta. We noted, however, that the TE-PGS graft underwent dilation until sufficient neotissue had been regenerated. This study investigated the mechanisms behind the observed dilation following TE-PGS vascular graft implantation in mice. We saw more pronounced dilation at the graft middle compared with the graft proximal and graft distal regions at 8 weeks postimplantation. Histological analysis revealed less degradation at the graft middle, although the remaining graft material appeared pitted, suggesting compromised structural and mechanical integrity. We also observed delayed cellular infiltration and extracellular matrix (ECM) deposition at the graft middle, corresponding with the area's reduced ability to resist dilation. In contrast, the graft proximal region exhibited greater degradation and significantly enhanced cellular infiltration and ECM regeneration. The nonuniform dilation was attributed to the combined effect of the regional differences in graft degradation and arterial regeneration. Consideration of these findings is crucial for graft optimization prior to its use in clinical applications.