Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs

Nat Commun. 2016 Sep 27:7:12951. doi: 10.1038/ncomms12951.

Abstract

Treatment of congenital heart defects in children requiring right ventricular outflow tract reconstruction typically involves multiple open-heart surgeries because all existing graft materials have no growth potential. Here we present an 'off-the-shelf' vascular graft grown from donor fibroblasts in a fibrin gel to address this critical unmet need. In a proof-of-concept study, the decellularized grafts are implanted as a pulmonary artery replacement in three young lambs and evaluated to adulthood. Longitudinal ultrasounds document dimensional growth of the grafts. The lambs show normal growth, increasing body weight by 366% and graft diameter and volume by 56% and 216%, respectively. Explanted grafts display physiological strength and stiffness, complete lumen endothelialization and extensive population by mature smooth muscle cells. The grafts also show substantial elastin deposition and a 465% increase in collagen content, without signs of calcification, aneurysm or stenosis. Collectively, our data support somatic growth of this completely biological graft.