Endothelium and biomaterials: morpho-functional assessments

Numerous synthetic biomaterials have been developed as vascular substitutes, but all materials, currently available, yield lower patency rates than do autogenous vascular grafts. Future investigations have to solve two problems concerning permanent or temporary artificial vascular substitution: 1. Graft healing reactions in the interface of biomaterial and surrounding human tissue. 2. Activation of blood clotting system and body defense reactions by contact of the artificial surface with blood. Concerning the first, the graft healing consists of a series of complex events including the incorporation by the perigraft fibrous tissue response. The degree of host tissue infiltration into the biomaterial depends on pore size, surface texture, anatomical location and the materialʹs biocompatibility. Our laboratory investigates the evaluation of biocompatibility by expression of stress proteins in the interface of biomaterials. In particular we could demonstrate that macrophages express different amounts of heat shock protein 70 (HSP70) in the interface of various vascular grafts implanted into sheep arteries. In comparison with standard cell-culture vitality tests HSP70 expression appears to be a more differenciated test-system than global parameters like cell growth and cell death. Furthermore, we speculate that specific induction of HSP70 before biomaterial implantation could prevent or reduce the toxic effect on the organism. Additionally studies are currently underway to evaluate whether endothelial cells express HSP70 in the interface of biomaterials. Concerning the second, all biomaterials investigated so far are more or less thrombogenic and initiate the bodys defense reaction. Only the endothelial cell is non thrombogenic and achieves this property by active metabolic processes. To develop an optimal vascular graft there are two possibilities: first raw materials without thrombogenic effect have to be found, second the artificial surface has to be modified in a nonthrombogenic one consisting of new chemical groups or hostʹs own endothelial cells. In this context a Brite project (P-2217) was carried out to develop an artificial blood vessel from synthetic polymer by seeding with human endothelial cells in our laboratories. Modified polymer surfaces were successfully seeded in vitro with human endothelial cells derived from the inner layer of veins and tested under stationary and dynamic blood flow conditions. The carrier polymer have been activated by functional groups in order to lodge spacer molecules of suitable length and density. These spacer molecules on their part are covalently linked to biological signals (e.g. cell-binding domain of fibronectin, GRGDS), which attract endothelial cells. Within the next decade our modified vascular prostheses have to be produced and tested in vivo with improved outer and inner surfaces.