Development of Tissue Engineered Heart Valves for Percutaneous Transcatheter Delivery in a Fetal Ovine Model

Jason Zakko; Kevin M Blum; Joseph D Drews; Yen-Lin Wu; Hoda Hatoum; Madeleine Russell; Shelley Gooden; Megan Heitkemper; Olivia Conroy; John Kelly; Stacey Carey; Michael Sacks; Karen Texter; Ellie Ragsdale; James Strainic; Martin Bocks; Yadong Wang; Lakshmi Prasad Dasi; Aimee K Armstrong; Christopher Breuer

doi:10.1016/j.jacbts.2020.06.009

Development of Tissue Engineered Heart Valves for Percutaneous Transcatheter Delivery in a Fetal Ovine Model

JACC Basic Transl Sci. 2020 Jul 29;5(8):815-828. doi: 10.1016/j.jacbts.2020.06.009. eCollection 2020 Aug.

Authors

Jason Zakko^{1

2}, Kevin M Blum^{1

3}, Joseph D Drews^{1

2}, Yen-Lin Wu⁴, Hoda Hatoum⁵, Madeleine Russell⁶, Shelley Gooden⁵, Megan Heitkemper^{1

3}, Olivia Conroy⁶, John Kelly^{1

7}, Stacey Carey⁷, Michael Sacks⁶, Karen Texter⁷, Ellie Ragsdale⁸, James Strainic⁹, Martin Bocks¹⁰, Yadong Wang⁴, Lakshmi Prasad Dasi⁵, Aimee K Armstrong⁷, Christopher Breuer^{1

2}

Affiliations

¹ Center for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
² Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio.
³ Department of Biomedical Engineering, Ohio State University, Columbus, Ohio.
⁴ Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York.
⁵ Coulter Department of Biomedical Engineering, Georgia Tech, Atlanta, Georgia.
⁶ Oden Institute for Computational and Engineering Sciences, University of Texas at Austin, Austin, Texas.
⁷ Heart Center, Nationwide Children's Hospital, Columbus, Ohio.
⁸ Department of OB/GYN-Maternal Fetal Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
⁹ Department of Pediatric Cardiology, University Hospitals Rainbow Babies and Children's Hospital, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
¹⁰ University Hospitals Rainbow Babies and Children's Hospital, School of Medicine, Case Western Reserve University, Cleveland, Ohio.

Abstract

This multidisciplinary work shows the feasibility of replacing the fetal pulmonary valve with a percutaneous, transcatheter, fully biodegradable tissue-engineered heart valve (TEHV), which was studied in vitro through accelerated degradation, mechanical, and hemodynamic testing and in vivo by implantation into a fetal lamb. The TEHV exhibited only trivial stenosis and regurgitation in vitro and no stenosis in vivo by echocardiogram. Following implantation, the fetus matured and was delivered at term. Replacing a stenotic fetal valve with a functional TEHV has the potential to interrupt the development of single-ventricle heart disease by restoring proper flow through the heart.

Keywords: EOA, effective orifice area; MPA, main pulmonary artery; Mn, molecular size; Mw, molecular weight; NOI, normalized orientation index; PCL, polycaprolactone; PDI, polydispersity index; PG, pressure gradient; RF, regurgitant fraction; RV, right ventricular/ventricle; SEM, scanning electron microscopy; TEHV, tissue-engineered heart valve; congenital heart disease; tissue-engineered heart valve; transcatheter heart valve; translational medicine.

Abstract

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