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

TLDR

Current grafts for pediatric right ventricular outflow tract reconstruction lack growth potential, requiring multiple surgeries. We developed an off‑the‑shelf vascular graft from donor fibroblasts in fibrin gel to enable somatic growth. The grafts were implanted as pulmonary artery replacements in three lambs and followed to adulthood. Ultrasound and histology showed grafts grew 56 % in diameter and 216 % in volume, lambs gained 366 % body weight, and explanted grafts displayed physiological strength, complete endothelialization, mature smooth muscle cells, 465 % collagen increase, and no calcification, aneurysm or stenosis, confirming somatic growth.

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.