Fast-degrading bioresorbable arterial vascular graft with high cellular infiltration inhibits calcification of the graft

Abstract

Objective Bioresorbable vascular grafts are biologically active grafts which are entirely reconstituted by host-derived cells through an inflammation-mediated degradation process. Calcification is a detrimental condition that can severely impact graft performance. Therefore, prevention of calcification is of great importance to the success of bioresorbable arterial vascular grafts. The objective of this study is to test whether fast degrading bioresorbable arterial grafts with high cellular infiltration will inhibit calcification of grafts. Methods We created two versions of bioresorbable arterial vascular grafts: 1) Slow Degrading (SD) grafts and 2) Fast Degrading (FD) grafts. Both grafts had the same inner layer composed of a 50:50 poly (l-lactic-co-ε-caprolactone) copolymer (PLCL) scaffold. However, the outer layer of SD grafts was composed of poly (l-lactic acid) (PLA) nano-fiber whereas the outer layer of FD grafts was composed of a combination of PLA and polyglycolic acid (PGA) nano-fiber. Both grafts were implanted in 8–10 week old female mice (n = 15 in the SD group, n = 10 in the FD group) as infra-renal aortic interposition conduits. Animals were followed for 8 weeks. Results Von Kossa staining showed calcification in 7 out of 12 grafts in the SD group, but zero in the FD group (P<.01, chi-square test). The cell number in the outer layer of FD grafts was significantly higher than SD grafts (SD: 0.87 ± 0.65 × 103/mm2 vs. FD: 2.65 ± 1.91 × 103/mm2, P=.02). Conclusions The fast degrading bioresorbable arterial vascular graft with high cellular infiltration into the scaffold inhibited calcification of grafts.

Host Response and Neo-Tissue Development during Resorption of a Fast Degrading Supramolecular Electrospun Arterial Scaffold

“…After 28 days, however, expression levels had declined to values that are equivalent to that of native aorta and remained constant throughout the course of the study, indicating a favorable down-regulation of TGF-β expression to avoid fibrosis. This is in line with recent studies, which demonstrated that timely scaffold degradation is essential to prevent fibrotic calcification of TEVGs in the arterial circulation [ 7 , 32 ].…”

Acellular Small-Diameter Tissue-Engineered Vascular Grafts

“…In order to inhibit the calcification of the graft, Sugiura et al [24] also combined the two methods of casting and electrospinning. Two versions of bioresorbable vascular grafts were created: slow-degrading (SD) grafts and fast-degrading (FD) grafts.…”

Preparation of Small‐Diameter Tissue‐Engineered Vascular Grafts Electrospun from Heparin End‐Capped PCL and Evaluation in a Rabbit Carotid Artery Replacement Model

“…How to adjust the mechanical properties of degrading vascular scaffolds not only maintaining the vascular integrity, but also matching with the regenerated neovascular tissue strength is a significant qualification for these eligible graft prostheses. Furthermore, it is noteworthy that the calcification would often lessen the long‐term efficacy of small‐diameter TEVGs …”