Ex vivo platforms for tissue-engineered heart valve assessment: a step towards clinical translation

Noemi Vanerio 1,2, Marco Stijnen1, Jurgen de Hart1, Bas de Mol2 and Linda Kock1

1 LifeTec Group BV, Eindhoven, The Netherlands

2 Dept. of Cardiothoracic Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Nowadays, a challenge in the cardiovascular field is to find effective methods for testing innovative approaches and devices, like tissue-engineered heart valves (TEHVs). Novel testing protocols, reducing animal experimentation and shortening the clinical translation path, without renouncing to in-depth analyses, are important factors in decreasing time and costs towards the development of these products. Therefore, LifeTec Group has developed three innovative platforms for testing different characteristics of TEHVs, as translational step in between in vitro and in vivo experiments.

The mechanical performance of heart valve prostheses, such as hydrodynamic performance and accelerated wear testing can be evaluated in a heart valve assessment platform. Prostheses are mounted in a fluid-dynamic circuit mimicking the compliance and resistance of the systemic circulation. Several parameters such as temperature, flow and heart rate are controllable.

Additionally, the platform allows for burst pressure testing, performance assessment with pulsatile flow under several conditions (infant, child, adult) and leakage testing.

In parallel, TEHVs can be tested in terms of biological response to tissue, cells and other factors. In our ex vivo vascular bioreactor blood vessels and tubular scaffolds, anastomosed to native vessels or seeded with cells, can be long-term cultured physiologically and treatments can be tested. It has been demonstrated that this platform can provide useful information on the interaction between the scaffold and tissue or cells despite of valve final design, being predictive for the in vivo situation.

The heart valve bioreactor is our third tool for testing combinations of physiological mechanical loading, hemodynamics and biological response. In this bioreactor, TEHVs are being cultured under physiological pressure or shear rate, allowing for realistic leaflets’ motion and loading conditions. Study of cell infiltration can be assessed under physiological pressure and flow and imaging of the TEHVs can be performed.

In conclusion, the use of innovative in vitro and ex vivo platforms to test new treatments in the cardiovascular tissue engineering field can be considered a helpful tool in design and development of tissue-engineered heart valves allowing for analysis of several parameters and filling the gap between in vitro and in vivo studies.

This work was supported by the European Commission within the Horizon 2020 Framework through the MSCA-ITN-ETN European Training Networks (project number 642458).