Different Biodegradation Rates of Tissue-Engineered Vascular Grafts in Small and Large Animal Models

Takuma Fukunishi ¹, Chin Siang Ong ¹, Cecillia Lui ¹, Jed Johnson ², Narutoshi Hibino ¹

¹ Johns Hopkins Hospital, Baltimore, USA; ² Nanofiber Solution Inc, Columbus, USA;

Date, time and location: 2018.05.25 13:30, Congress Hall, 2F–B

Abstract

Objective: Tissue-engineered vascular grafts (TEVGs) offer a potential strategy for overcoming complications of current artificial grafts by providing biodegradable scaffolds, for autologous cells to proliferate and provide physiologic functionality of neovessels. Most TEVG studies were conducted in small animals at first, and then applied to large animal models. However, little is known regarding the differences in reactions to biomaterials between small and large animal models. The purpose of this study is to compare the biodegradable profiles of TEVGs in a small versus large animal model.

Method: Two types of electrospun scaffolds were fabricated using polycaprolactone (PCL)/Chitosan and polyglycolic acid (PGA)/poly(L-lactide-co-caprolactone)(PLCL) co-polymers. The PCL/Chitosan TEVGs were implanted as abdominal aorta interposition conduits in rats (n=5) and as carotid artery interposition conduits in sheep (n=3). The PGA/PLCL TEVGs were implanted as inferior vena cava (IVC) interposition grafts in both rats (n=5) and sheep (n=3). The TEVGs were harvested at 6 months to evaluate patency, neotissue formation, remodeling scaffold and macrophage infiltration.

Result: All TEVGs were patent without complications (aneurysm, rupture) at 6 months. There were significantly higher extracellular matrix formation, more mature collagen formation, and higher macrophage infiltration TEVGs implanted in large animals (macrophage infiltration = PCL/Chitosan; 179±29/mm2 vs. 37±8/mm2, p<0.001, PGA/PLCL; 316±111/mm2 vs. 133±30/mm2, p=0.011). There was significantly less remaining scaffold in TEVGs implanted in large animals, in both arterial and venous circulatory systems (PCL/Chitosan; 7±4% vs. 27±5%, p <0.001, PGA/PLCL; 0.8±0.3% vs. 22±2%, p<0.001). 

Conclusion: The profiles of degradation and neotissue formation of TEVGs are significantly different between small and large animal studies. It is important to understand these differences for the development of TEVGs for clinical applications.