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.
Highlights
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
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
Summary
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. The application of a competent, readily available conduit, with the ability to grow with the child, would eliminate the need for multiple operations and the morbidities associated with these procedures, possibly benefiting more than 1,000 pediatric patients annually in the USA4 It would dramatically reduce the financial burden on the health care system associated with currently used conduits that require periodic replacement to accommodate child growth. Pioneering research in this field has been conducted by Shin’oka et al.[11] with the landmark report of reconstruction of an occluded pulmonary artery in a 4-year old patient with a degradable synthetic polymer tube of the copolymer polylactic acid/polycaprolactone seeded with autologous cells. Investigators have conducted extensive research in the mouse aorta model to elucidate the role of the seeded cells and the host response[15,16,17,18,19,20,21,22]
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