In vivo behavior of epoxy-crosslinked porcine heart valve cusps and walls

J Biomed Mater Res. 2000;53(1):18-27. doi: 10.1002/(sici)1097-4636(2000)53:1<18::aid-jbm3>;2-j.


Calcification limits the long-term durability of xenograft glutaraldehyde-crosslinked heart valves. In this study, epoxy-crosslinked porcine aortic valve tissue was evaluated after subcutaneous implantation in weanling rats. Non-crosslinked valves and valves crosslinked with glutaraldehyde or carbodiimide functioned as control. Epoxy-crosslinked valves had somewhat lower shrinkage temperatures than the crosslinked controls, and within the series also some macroscopic and microscopic differences were obvious. After 8 weeks implantation, cusps from non-crosslinked valves were not retrieved. The matching walls were more degraded than the epoxy- and control-crosslinked walls. This was observed from the higher cellular ingrowth with fibroblasts, macrophages, and giant cells. Furthermore, non-crosslinked walls showed highest numbers of lymphocytes, which were most obvious in the capsules. Epoxy- and control-crosslinked cusps and walls induced lower reactions. Calcification, measured by von Kossa-staining and by Ca-analysis, was always observed. Crosslinked cusps calcified more than walls. Of all wall samples, the non-crosslinked walls showed the highest calcification. It is concluded that epoxy-crosslinked valve tissue induced a foreign body and calcification reaction similar to the two crosslinked controls. Therefore, epoxy-crosslinking does not represent a solution for the calcification problem of heart valve bioprostheses.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bioprosthesis*
  • Calcinosis / etiology
  • Calcinosis / pathology
  • Carbodiimides
  • Coated Materials, Biocompatible*
  • Cross-Linking Reagents
  • Epoxy Compounds
  • Glutaral
  • Heart Valve Prosthesis*
  • Male
  • Materials Testing
  • Prosthesis Failure
  • Rats
  • Rats, Sprague-Dawley
  • Swine


  • Carbodiimides
  • Coated Materials, Biocompatible
  • Cross-Linking Reagents
  • Epoxy Compounds
  • Glutaral