Reduced calcification of bioprostheses, cross-linked via an improved carbodiimide based method

Glutaraldehyde fixation of bioprosthetic tissue has been used successfully for almost 40 years. However, it is generally recognized that glutaraldehyde fixation of bioprostheses is associated with the occurrence of calcification. Accordingly, many efforts have been undertaken to develop techniques for the fixation of bioprostheses, which will not lead to calcification. Here we describe a new improved carbodiimide based cross-linking method. Rather than cross-linking the tissue through its free primary amine groups, these groups were first blocked with butanal and the tissue was then cross-linked by means of carbodiimide activation of tissue carboxylic acid groups followed by a reaction with a poly(propylene glycol)bis 2-(aminopropyl) ether, (Jeffamine(TM)). It was demonstrated that cross-linked porcine leaflets had a calcification of less than 1 mg/g tissue after 8 weeks sub-dermal implantion in rats. Furthermore, aortic wall calcification was reduced to 50 mg/g, compared to standard glutaraldehyde fixed tissue, which showed 120 mg/g tissue calcification in the 8 weeks calcification model used. (C) 2003 Elsevier Ltd. All rights reserved.