Our Research Aims

In recent years experimental research at the German Heart Center Berlin has concentrated on the artificial production of complex tissue, known as tissue engineering. The aim is to produce artificial tissue and organs in vitro and so open up new treatment possibilities.

Despite the great progress made in cardiovascular tissue engineering, there are as yet no heart valve prostheses that can integrate into the surrounding tissue as well as having the potential of regenerating and of growing with pediatric patients’ development. Our researchers are working on finding a suitable source of human cells and on developing an optimal three-dimensional scaffold material in valve form. Further, they are researching different in vitro cell culture conditions that lead to the growth of tissue on the scaffolds.

Which Types of Cell Do We Use?

Our researchers favor autologous cells (those from the patient’s own body) to avoid immunological problems. Since the tissue engineering of heart valves cannot use vale biopsies from living donors, cells with similar physiology must be found.

Tissues from the largest superficial vein of the leg (great saphenous vein) or from the beginning of the aorta or from bone marrow are suitable sources of cells. Other prenatal and neonatal cell sources have been investigated for their suitability, including the umbilical cord. This is the approach followed by our working group. The umbilical cord has that advantage that it is, after the birth, superfluous tissue and there are no reservations about its use from an ethical standpoint. To gain autologous cells no further procedure on the patient is necessary. Our researchers have been able to show that the vessel wall cells of the human umbilical cord may be suitable for the tissue engineering of heart valves and vessels. Cells from the umbilical cord are not stem cells but are differentiated cells that are found in similar form in heart valves.

Development of the Scaffold Material

One of the challenges in the tissue engineering of heart valves is developing scaffolds that can be shaped into valve form and on which cells can grow. At present our researchers are testing different materials for their suitability: natural materials such as collagen or fibrin and synthetic such as resorbable polymers and stable materials. The focus is on resorbable polymers as scaffold structures, but xenografts are also used. The polymers are prepared in our laboratory, seeded with cells and examined. The main challenge lies in exactly reproducing a three-dimensional scaffold. Procedures from the textile industry and from 3D printing are being used.

Each material has advantages and disadvantages in terms of the special requirements that must be fulfilled for heart valve scaffolds. In particular replacement valves for the left side of the heart will be subjected to extreme pressure and blood flow conditions. In a current research project we are therefore developing new procedures for the production of a heart valve form on the basis of resorbable scaffold material. The material must be optimally adapted to the recipient, degrade completely without toxic effects and in a predictable time, and at the same time be gradually replaced by the body’s own extracellular matrix structures (the remodeling process).

Development and Manufacture of Bioreactors

In order to produce a functional tissue construction the cells must be cultivated on the scaffold under conditions resembling the native environment. The mechanical forces of the medium flowing through the valve (flow rates, pulse pressure) play an important role.
Our laboratory first developed bioreactors for the engineering of human heart valves, vessels and patches in the year 2000. Since then they have been modified and optimized. Currently a bioreactor for the expansion of adherent cells and a so-called pulse bioreactor, in which the heart valve scaffolds seeded with cells are conditioned, are in use.