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Tissue Engineering in Cardiovascular Surgery

For some years, one branch of experimental research at the DHZB has been the fascinating area of the artificial production of complex tissues, known as tissue engineering.

 

Engineering of heart valve prostheses using autologous cells

For heart valve replacement, at present mechanical and biological prostheses are used. These function well but consist of material that is foreign to the body and have the disadvantage that they cannot grow in size. In children and teenagers this is a serious disadvantage as they “grow out of” the replacement valve and need several corrective operations. A potential solution to this problem may lie in the tissue engineering of replacement cardiovascular tissue. The principle of tissue engineering is to use autologous cells (cells from the patient’s own body) to produce viable, functioning replacement tissue that would become integrated into the surrounding tissue, grow with it and form highly durable valves (Fig. 1).

Abb.1: Schematische Darstellung des Tissue Engineering Prinzips.

Fig. 1: The principle of tissue engineering

 

The constructed valve fabricated from human cells and scaffold material, for example a biodegradable polymer, must be produced under optimal in vitro conditions so that it can be later be transplanted into the heart of the patient from whom the cells were taken.

A particular focus of research of the DHZB laboratory is the identification of a source of suitable cells. Since it is not possible to use cells from heart valves themselves, cells must be utilized that are as similar as possible to heart valve cells. In the past few years human vascular umbilical cord cells have been evaluated as a source of autologous cells for cardiovascular tissue engineering. The umbilical cord is normally discarded as superfluous tissue after birth. It has several long blood vessels and can be used to harvest a very large number of vascular cells without the patient undergoing any harvesting procedure. These cells can be stored in liquid nitrogen until required (Fig. 2).

 

Abb.2: Kryokonservierung vaskulärer Nabelschnurzellen

Fig. 2: Cryopreservation of vascular umbilical cord cells

 

In our laboratory the vascular umbilical cord cells are characterized using immunohistological and molecular biological methods (e.g. FACS analysis, transmission electron microscopy). The main target group for the possible use of these cells is newborn children with congenital heart valve defects. In older children and teenagers other suitable cells (mesenchymal precursor cells) are to be isolated from the patients’ own bone marrow and used to engineer heart valves.

A further focus of our research laboratory is the development of cell culture systems and “bioreactors” in which the heart valve construct is conditioned by mechanical means. By rotating the reactor, for example, it is possible for the cells to be evenly distributed on the scaffold material (Fig. 3).

 

Fig. 3: Cell-seeding device

Fig. 3: Cell-seeding device: (1) rotating machine; (2) base frame with rubber rollers; (3) acrylic bowl with balance weight; (4) cell suspension inlet; (5) lid of the bowl; (6) cylindrical cell-seeding chamber

 

These are the preconditions for the formation of tissue-like united cell structures on a complex three-dimensional scaffold like that for a heart valve. Influenced by pressure and flow in the bioreactor, the cells align in a particular direction. Thus the formation of extracellular matrix proteins is encouraged, which is very important for the development of cell tissue (Fig. 4).

Versuchsaufbau eines Bioreaktors.

Fig .4: Bioreactor test

In parallel with this research, the in vitro conditions for fabricating tissue engineered valves are constantly being modified and optimized. The aim is to provide the cells with the greatest possible nutrient supply so that the growth process can be accelerated. In future, viable human heart valves consisting of autologous cells, with the ability to grow, are to be applied in cardiac surgery.
 

Our team

Our laboratory for tissue engineering has since 2000 been part of the Department of Cardiothoracic and Vascular Surgery, headed by  Prof. Dr. med. Dr. h.c. R. Hetzer.

Members of the working group are:

Dr. rer. nat. Cora Lüders-Theuerkauf (head)

lueders@dhzb.de; 030 4593 2164

Dipl. Ing. Anne Reichardt

areichardt@dhzb.de; 030 4593 2154/2163/2164


Bianca Polchow, MSc. (Biotechnology)

polchow@dhzb.de; 030 4593 2154/ 2163/ 2164

Nora Döhnert

doehnert@dhzb.de; 030 4593 2154/ 2163/ 2164

Jeevan Reddy Sankaramaddi

sankaramaddi@dhzb.de; 030 4593 2154/ 2163/ 2164

We also have cooperation agreements with different national and international working groups.

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