Cross-linking of collagen-based materials

An example of a collagen-based tissue is the aortic heart valve. A variety of pathological processes can lead to heart valve malfunction and this is usually associated with degenerative changes of the tissue. The most commonly used types of prosthetic valves are mechanical and tissue valves. One major disadvantage in the use of mechanical valves is the need for continuous anticoagulation therapy to minimize the risk of thrombosis, whereas tissue valves can be used without anticoagulants. Tissue valves are constructed from porcine aortic valves or bovine pericardium and are treated with glutaraldehyde to introduce cross-links. However, the durability of bioprostheses is limited due to calcification, which leads to tearing and rupture of the material. The factors and the mechanisms of calcification are still not fully understood. It was the objective of this study to develop and to optimize new cross-linking methods for the stabilization of collagen-based tissues resulting in materials which are biocompatible and non-calcifying and do not evoke cytotoxic reactions. A model tissue, dermal sheep collagen (DSC) which consists of 100 % fibrous collagen type I, was chosen to study the cross-linking process in more detail. Furthermore, the relation between the cross-linking conditions and the material properties obtained was studied. DSC was previously used in the development of new biomaterials. New cross-linking methods such as the use of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) in the presence of N-hydroxysuccinimide (NHS) were successfully developed and led to biocompatible, non-calcifying materials.