Bioengineered Heart Valves Guide Tissue Remodeling

A new study suggests that tissue-engineered heart valve (TEHVs) designed with the aid of computer simulations could provide long-term functionality.

Researchers at the University of Zurich (UZH; Switzerland), Eindhoven University of Technology (TUE; The Netherlands), and other institutions used computational modeling to design regenerative TEHVs grown on polymer scaffolds seeded with vascular cells. After four weeks in a bioreactor, the grafts were decellularized prior to implantation as pulmonary valve replacements in sheep, using a minimally invasive transcatheter technique. The TEHVs were then monitored for one year using multi-modal in-vivo imaging and comprehensive tissue remodeling assessments.

At follow-up, 9 of the 11 grafts remained functional. Computational modeling predicted that the valve leaflets would shorten during dynamic remodeling before reaching equilibrium, which was confirmed in the sheep. The computer simulation also showed that TEHV failure could be predicted in advance for non-physiological pressure loading. The researchers suggest that future tissue engineering strategies should include computational simulation so as to lead to more predictable clinical translation. The study was published on May 9, 2018, in Science Translational Medicine.

“One of the biggest challenges for complex implants such as heart valves is that each patient's potential for regeneration is different. There is therefore no one-size-fits-all solution,” said senior author Professor Simon Hoerstrup, MD, PhD, of UZH. “Thanks to the simulations, we can optimize the design and composition of the regenerative heart valves and develop customized implants for use in therapy.”

Surgical correction of chronic heart disease (CHD) defects such as Tetralogy of Fallot and pulmonary atresia has increased dramatically. But despite excellent long-term survival, they typically require multiple operative procedures until adulthood, as the homograft pulmonary artery conduits or BJV grafts have no ability to grow and remodel with the somatic growth of the child. Additionally, an intense inflammatory reaction to these materials commonly occurs, resulting in early calcification and failure, leading typically to the need for 5-7 operative procedures.

Related Links:
University of Zurich
Eindhoven University of Technology