Nerve regeneration and elastin formation within poly(glycerol sebacate)-based synthetic arterial grafts one-year post-implantation in a rat model

Abstract

The objective of this study was to evaluate the long term performance of cell-free vascular grafts made from a fast-degrading elastic polymer. We fabricated small arterial grafts from microporous tubes of poly(glycerol sebacate) (PGS) reinforced with polycaprolactone (PCL) nanofibers on the outer surface. Grafts were interpositioned in rat abdominal aortas and characterized at 1 year post-implant. Grafts remodeled into “neoarteries” (regenerated arteries) with similar gross appearance to native rat aortas. Neoarteries mimic arterial tissue architecture with a confluent endothelium and media and adventita-like layers. Patent vessels (80%) showed no significant stenosis, dilation, or calcification. Neoarteries contain nerves and have the same amount of mature elastin as native arteries. Despite some differences in matrix organization, regenerated arteries had similar dynamic mechanical compliance to native arteries in vivo. Neoarteries responded to vasomotor agents, albeit with different magnitude than native aortas. These data suggest that an elastic vascular graft that resorbs quickly has potential to improve the performance of vascular grafts used in small arteries. This design may also promote constructive remodeling in other soft tissues.

Tyramine functionalization of poly(glycerol sebacate) increases the elasticity of the polymer

“…It will help the scaffold retain its integrity for use in a mechanically dynamic environment upon implantation. 7, 33 To examine the elasticity and ability to recover from reversible deformations, cyclic loading mechanical (hysteresis) tests were performed on dog-bone samples of the PGS control, PGS-TA 15 , and PGS-TA 25 elastomers (Fig. 4A and Fig.…”

“…35 We made the scaffolds by curing at 150 °C for 24 h because this condition has been established to make PGS vascular graft in our lab. 7, 33 75–150 μm NaCl salt was used as the template to give a nearly identical porous structure and pore size of both scaffolds (Fig. 6C, D).…”

Elastomeric and mechanically stiff nanocomposites from poly(glycerol sebacate) and bioactive nanosilicates

“…[35,37,38] Comparing to other widely used synthetic polymers such as poly(lactic acid)(PLA) and poly(lactic-co-glycolic acid)(PLGA)-based materials, PGS triggered lower inflammatory responses and minimal fibrous encapsulation. [35][36][37] As a consequence, PGS-based scaffolds are explored for various soft tissue engineering applications, including vascular graft [39][40][41], nerve guide [42], cardiac patch [43], cartilage tissue [44], and retinal transplantation [45]. In addition, it has been reported that PGS supported phenotypes of osteoblasts in vitro and was a promising osteoconductive substrate for bone tissue engineering application.…”

Tissue engineered vascular grafts: Origins, development, and current strategies for clinical application

“…Owing to both rapidly degrading graft material and increased porosity the authors demonstrated that: cell adhesion was timely, graft material was safe for implantation without leakage or rupture, and the remodeling process occurred at a rapid rate, resulting in a robust and compliant neo-artery (with intact three-layered vessel architecture). In terms of long-term results in rodents, the same group has demonstrated that, at one year post-implant, the cell-free approach maintained gross appearance similar to native aorta, which similar tissue architecture and response to vasoactive substances as native arteries [33]. This newer, cell-free approach, coupled with the easy handling characteristics of these grafts, has challenged prior conventional thinking regarding the remodeling process -that it should be ''slow'' and hence grafts should be designed to be somewhat resistant to remodeling in the immediate post-implantation period [32,33].…”