Evaluation of a biodegradable scaffold‐ and stem cell‐based tissue‐engineered vascular graft in rat and pig models

Abstract

Bi‐layered, synthetic, biodegradable, elastomeric tubular scaffolds comprised of a highly porous medial layer and an external, reinforcing fibrous layer were bulk‐seeded with allogeneic (rat studies) or autologous (pig studies), LacZ+ muscle‐derived stem cells (MDSCs) using a previously described rotational vacuum seeding device, then placed in spinner flask culture for 24 hours. Cellular integration was assessed via nuclear and cytoskeletal staining. Constructs were implanted as interposition grafts in the abdominal aorta of rats for 8 weeks or carotid arteries of pigs for 30 days. Angiogram, histology, immunostaining and SEM were performed at time of explant. In the rat studies, cell‐seeded constructs showed a higher patency rate than the unseeded controls (63% vs. 0%). A smooth muscle‐like layer of cells was observed near the luminal surface of the constructs. LacZ+ cells were shown to be engrafted in the remodeled construct. A confluent layer of vWF‐positive cells was observed in the lumen of seeded constructs, whereas controls showed thrombosis. In the pig studies to date, all TEVGs were patent, though intimal hyperplasia was observed. We have demonstrated the successful integration of allogeneic stem cell‐based TEVGs in a rat model and the feasibility of a completely autologous approach in a pig model. Support from NIH BRP #R01 HL069368.