Different degradation rates of nanofiber vascular grafts in small and large animal models

Abstract

Nanofiber vascular grafts have been shown to create neovessels made of autologous tissue, by in vivo scaffold biodegradation over time. However, many studies on graft materials and biodegradation have been conducted in vitro or in small animal models, instead of large animal models, which demonstrate different degradation profiles. In this study, we compared the degradation profiles of nanofiber vascular grafts in a rat model and a sheep model, while controlling for the type of graft material, the duration of implantation, fabrication method, type of circulation (arterial/venous), and type of surgery (interposition graft). We found that there was significantly less remaining scaffold (i.e., faster degradation) in nanofiber vascular grafts implanted in the sheep model compared with the rat model, in both the arterial and the venous circulations, at 6 months postimplantation. In addition, there was more extracellular matrix deposition, more elastin formation, more mature collagen, and no calcification in the sheep model compared with the rat model. In conclusion, studies comparing degradation of vascular grafts in large and small animal models remain limited. For clinical translation of nanofiber vascular grafts, it is important to understand these differences.

Tissue-Engineered Carotid Artery Interposition Grafts Demonstrate High Primary Patency and Promote Vascular Tissue Regeneration in the Ovine Model

“…Intriguingly, these results fully correspond to a recent paper which also reported a striking difference in the degradation rates of TEVGs between small and large animal models [44]. Similar to our previous and present research, this study employed rat abdominal aorta and sheep carotid artery interposition models for the implantation of PCL/chitosan vascular graft [44]. In keeping with the abovementioned results, ovine prostheses demonstrated a pronounced degradation concurrently with ECM deposition and absence of calcification at 6 months postimplantation, in contrast to the rat model [44].…”

“…In rats, all grafts were intact 12 months postimplantation and did not display any signs of aneurysm formation [27,32]. Intriguingly, these results fully correspond to a recent paper which also reported a striking difference in the degradation rates of TEVGs between small and large animal models [44]. Similar to our previous and present research, this study employed rat abdominal aorta and sheep carotid artery interposition models for the implantation of PCL/chitosan vascular graft [44].…”

The Role of Immunomodulation in Vein Graft Remodeling and Failure

“…An interesting new alternative could be the use of tissue-engineered blood vessels (TEBV) as grafts. Several variants of TEBV are described, usually based on the use of a scaffold to which vascular (precursor) cells are attracted to or seeded on [103][104][105].…”

“…The degradation rate orchestrates the cell infiltration and subsequently remodeling. This delicate balance between nanofiber degradation and neovessel tissue is different between species and requires optimization for the enhancement of translational capacity [103]. An alternative can be the in situ TEBV, where fibroblast and progenitor vascular cells form a vascular-like tube around a solid scaffold that can be used as a conduit for (arterio) venous grafting [104].…”

Resorbable vascular grafts show rapid cellularization and degradation in the ovine carotid

“…Additionally, recently published work has highlighted interspecies differences in inflammation and remodeling of vascular grafts. When identical grafts were implanted in sheep or rats, sheep demonstrated more aggressive inflammation and faster biomaterial degradation (Fukunishi et al, 2019). This may be due to the greater platelet response observed in large animals that recruits neutrophils and initiates the inflammatory process (Rossaint & Zarbock, 2015).…”