Figure 2: Piece of a porcine heartvalve modified with a surface attached polymer network (swollen in water)

Polymer layers for the re-endothelialization of porcine heart valves

[Project with Prof. Dr. Manfred Dahm from the Department of Cardiothoracic and Vascular Surgery at the University Hospital in Mainz, Germany]

The search for suitable replacements for human heart valves is a highly pursued field of research in medicine as well as in materials research. One approach is to use heart valves from biological sources such as porcine heart halves which are superior in hemodynamics to mechanical valves and do not require anticoagulation treatment. However, due to the need to improve the mechanical properties of the valves and to suppress xenophobic reactions of the body against the implant, they are usually treated with glutaraldehyde which changes the surface chemistry and leads to crosslinking of the collagen fibres of the valves. The drawback of this procedure is that the valves lose their cellular coverage and in addition toxic remnants of the aldehyde prevent re-endothelialization. This process finally leads to calcification and reduces the life time of the valve to 7 – 10 years in an adult. It has been shown previously that the seeding of endothelial cells on the implant surfaces significantly reduces the calcium uptake.1-2 But cell growth on the surfaces is rather difficult due to their toxicity.

Our approach to make the collagen surfaces of porcine heart valves again attractive for endothelial cell growth is to mask the toxic groups by covering the surface with a thin polymer coating. As these layers have to be stable in an aqueous environment, a firm adhesion of the polymers to the bioimplant surface is mandatory. Clearly the best way to achieve this stability is to covalently attach the polymers to the substrate. To allow for such conditions, we use a photochemical approach by which we can immobilize biocompatible polymers on the valve surfaces. This approach is schematically depicted in Figure 1.

Figure 1: Strategy for masking toxic glutaraldehyde (GDA) remnants on porcine heart valve surfaces by compatibilizing polymer layers.

Copolymers carrying benzophenone units are firstly prepared and deposited on the valve surfaces. Upon irradiation with UV light the copolymers react through a radical coupling reaction of benzophenone moities with each other and to the adjacent valve surfaces, i.e., collagen surfaces(“photocrosslinking process”) as shown in Figure 2.

References
1) M. Dahm, D. Pruefer, O. Oster, E. Groh, H. Oelert, J. Heart Valve Disease, 5 (1996) 148.
2) A. Bader, T. Schilling, O.E. Teebken, G. Brandes, T. Herden, G. Steinhoff, A. Haverich, Eur. J. Cardiothorac. Surg., 14 (1998) 279.

This project is sponsored by the Deutsche Forschungsgemeinschaft (DFG).