Author + information
- Received March 30, 2020
- Revision received June 10, 2020
- Accepted June 10, 2020
- Published online August 24, 2020.
- Jason Zakko, MD, MSa,b,∗,
- Kevin M. Blum, MSa,c,∗,
- Joseph D. Drews, MD, MSa,b,∗,
- Yen-Lin Wu, MSd,∗,
- Hoda Hatoum, PhDe,∗,
- Madeleine Russell, BSf,∗,
- Shelley Gooden, MSe,
- Megan Heitkemper, MSa,c,
- Olivia Conroy, BSf,
- John Kelly, MDa,g,
- Stacey Carey, RNg,
- Michael Sacks, PhDf,†,
- Karen Texter, MDg,†,
- Ellie Ragsdale, MDh,†,
- James Strainic, MDi,†,
- Martin Bocks, MDj,†,
- Yadong Wang, PhDd,†,
- Lakshmi Prasad Dasi, PhDe,†,
- Aimee K. Armstrong, MDg,† and
- Christopher Breuer, MDa,b,†∗ ()
- aCenter for Regenerative Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, Ohio
- bDepartment of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio
- cDepartment of Biomedical Engineering, Ohio State University, Columbus, Ohio
- dMeinig School of Biomedical Engineering, Cornell University, Ithaca, New York
- eCoulter Department of Biomedical Engineering, Georgia Tech, Atlanta, Georgia
- fOden Institute for Computational and Engineering Sciences, University of Texas at Austin, Austin, Texas
- gHeart Center, Nationwide Children’s Hospital, Columbus, Ohio
- hDepartment of OB/GYN-Maternal Fetal Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio
- iDepartment of Pediatric Cardiology, University Hospitals Rainbow Babies and Children's Hospital, School of Medicine, Case Western Reserve University, Cleveland, Ohio
- jUniversity Hospitals Rainbow Babies and Children's Hospital, School of Medicine, Case Western Reserve University, Cleveland, Ohio
- ↵∗Address for correspondence:
Dr. Christopher Breuer, Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, WB4154, Columbus, Ohio 43205.
• A fully biodegradable fetal valve was developed using a zinc-aluminum alloy stent and electrospun PCL leaflets.
• In vitro evaluation of the valve was performed with accelerated degradation, mechanical, and flow loop testing, and the valve showed trivial stenosis and trivial regurgitation.
• A large animal model was used for percutaneous delivery of the valve to the fetal pulmonary annulus.
• Following implantation, the valve had no stenosis or regurgitation by echocardiography, and the fetal sheep matured and was delivered at term with the tissue-engineered valve.
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.
- congenital heart disease
- tissue-engineered heart valve
- transcatheter heart valve
- translational medicine
↵∗ Drs. Zakko, Blum, Drews, Wu, Hatoum, and Russell contributed equally to this work and are joint first authors.
↵† Drs. Sacks, Texter, Ragsdale, Strainic, Bocks, Wang, Dasi, Armstrong, and Breuer contributed equally to this work and are joint senior authors.
This work was supported by TL1TR001069 (to Dr. Zakko), T32HL098039 (to Dr. Kelly), and TL1TR002735 (to Ms. Heitkemper). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received March 30, 2020.
- Revision received June 10, 2020.
- Accepted June 10, 2020.
- 2020 The Authors