Research ArticleTissue Engineering

Spontaneous reversal of stenosis in tissue-engineered vascular grafts

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Science Translational Medicine  01 Apr 2020:
Vol. 12, Issue 537, eaax6919
DOI: 10.1126/scitranslmed.aax6919

Lessons in graft remodeling

Tissue-engineered grafts have the capacity to grow and remodel after implantation, which could confer considerable benefit to individuals with congenital heart disease. After a promising clinical trial in Japan, Drews et al. implanted tissue-engineered vascular grafts (TEVGs) as cardiac conduits in children with single-ventricle anomalies in the United States. The grafts, polymeric scaffolds seeded with autologous bone marrow–derived cells, showed surprising evidence of stenosis within 8 months after implantation, halting the clinical trial. Computational studies predicted the early stenosis, which was also observed after TEVG implantation in sheep. In silico and in vivo studies confirmed that early stenosis resolved via inflammation-driven graft remodeling without surgical intervention within 1 year after implantation. Results uncover a mechanism of reversible stenosis in TEVGs and support the value of computational modeling for informing graft design and accelerating safe translation of cardiovascular tissue–engineered products.

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