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Posted on July 17, 2018 by  & 

Long term in vivo performance of tissue engineered heart valves

The aim of tissue engineering and regenerative medicine is to create living biological tissue that can repair and replace damaged tissues in the body, something that cannot be achieved by medicine and medical procedures. In May 2018, a group of researchers out of the University of Zurich, the Technical University Eindhoven and the Charité Berlin have published in Science Translation Medicine their successes in creating a lasting tissue engineered heart valve (TEHV) in a clinically and regulatory-relevant sheep model.
 
IDTechEx have been following the topic of Tissue Engineering over the past year. For more information on the topic, please refer to IDTechEx's report Tissue Engineering 2018 - 2028: Technologies, Markets, Forecasts.
 
Currently, patients whose heart valves fail to function properly can receive either artificial heart valves (made from metals, ceramics, and polymers), or bioprosthetic heart valves with both synthetic and biological components from animals such as cows and pigs. However, these solutions have several drawbacks. Though mechanical valves last longer, often for a patient's entire lifetime, patients are required to take anticoagulant medication to prevent the formation of blood clots. On the other hand, while bioprosthetic heart valves do not cause blood clots, they have a limited longevity and are thus only recommended for older patients. Neither type of heart valve replacement has regeneration ability. This is especially problematic for pediatric patients, as their artificial heart valves must be regularly replaced as they outgrow the implants. Thus, tissue engineered heart valves, being living, have the potential to solve this limitation while also avoiding a lifetime of anticoagulation medication.
 
 
Though much research has gone into tissue engineering heart valves, previous work has faced many stumbling blocks in creating lasting constructs. Biological work, particularly, work with cells, is highly complex and variable. Previous attempts at creating TEHV have met with limited long-term performance due to uncontrolled cell behavior after transplantation.
 
Here, the researchers have used computational modeling to better understand the behavior of the heart valves in vivo and the circumstances that lead to failure. Though this has been conducted extensively in the design of artificial heart valves, it has only been used rarely in the study of TEHV. By studying the strains and stresses placed on the tissue during difference phases of the heartbeat, the researchers found that a change in geometry could lead to an increase in stretch of the valve, thus reducing the likelihood of valve failure by leaflet retraction.
 
Distal (left) and proximal (right) view of the TEHV after 4 weeks of culturing in vivo. (Source: Emmert et al., Science Translational Medicine, 2018).
 
Guided by this design, TEHVs were constructed from polyglycolic-acid meshes and seeded with ovine vascular-derived cells. The seeded constructs were incubated in a bioreactor system for 4 weeks to allow the cells to grow and excrete extracellular matrix (ECM). The construct was cultured under pulsatile flow with geometry constraining inserts to maintain the desired shape during incubation. After 4 weeks, the construct was then subject to detergent treatment to remove the cells while maintaining the ECM structure.
 
 
Implantation of the TEHV was conducted on 10 adult sheep and left in place for 1 year with imaging conducted 1 week after implantation and then monthly to 1 year. At 1 year, the valves showed repopulation by cells, and 9 out of the 10 TEHVs were found to have preserved their function and behaved comparably to native valves. This is a significant achievement for TEHVs, and a milestone in demonstrating that computationally inspired designs, in conjunction with in vitro experiments, can lead to improved in vivo outcomes.
 
IDTechEx believes that this, along with many other technological advancements in tissue engineering heart valves, will have a profound impact on patients requiring heart valve replacement. However, TEVH are unlikely to come to the market within the next 5 - 10 years, as more preclinical studies are required before entering a lengthy clinical trials process. Moreover, companies commercializing tissue engineering therapies face many challenges on the road between bench to bedside. These challenges include (but are not limited to) ensuring reproducibility and scalability of production, navigating the costly clinical trials process, and winning support from payers and physicians.
 
 
Sources:
Press release, University of Zurich
Emmert, M. Y., Schmitt, B. A., Loerakker, S., Sanders, B., Spriestersbach, H., Fioretta, E. S., ... Hoerstrup, S. P. (2018). Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model. Science Translational Medicine, 10(440).
DOI: 10.1126/scitranslmed.aan4587
 

Authored By:

Research Director, Personnel Lead

Posted on: July 17, 2018

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