Ghent University, Belgium
Pamela Somers has completed her PhD in Medical Sciences at the age of 29 years from Ghent University. At present, she is performing Postdoctoral research in cardiac tissue engineering at Ghent University. She has published more than 29 papers in reputed journals.
Background: Currently, an effective crosslinking reagent to treat xenogenic de-cellularized heart valve matrices is lacking. Matrices still elicit an intense cell-mediated immune response and calcification. The aim of this study was to evaluate the crosslinking effect of Quercetin, Catechin, Caffeic Acid and Tannic acid on porcine aortic valve matrices.
Materials and Methods: Cytotoxicity of the different crosslinkers was evaluated. Mechanical properties of crosslinked porcine matrices and control matrices (non-fixed) were examined by tensile strength testing. Cytocompatibility of the fixed matrices was examined. Crosslinked and control matrices were implanted subcutaneously in Wistar rats (n=9). After 2 weeks the explants were examined by light microscopy. Calcium content was determined using inductively coupled plasma-mass spectrometry. Antibody reaction against porcine tissue in the rat serum was determined.
Results: Cytotoxicity studies demonstrated that crosslinkers, even at high concentrations, did not inhibit cell viability. All crosslinkers, except Tannic acid, improve mechanical strength of acellular porcine matrices. Moreover, tensile strength of Quercetin fixed matrices was comparable with glutaraldehyde-fixed leaflets. Light microscopic evaluation showed that crosslinked matrices showed only a mild lymphocytic inflammatory reaction. Furthermore, Quercetin fixed leaflets exhibited a well preserved matrix without infiltration of CD3+ cells. Calcium levels after 2 weeks were for controls (non-fixed): 206.33µg/mg; Quercetin: 151.33µg/mg; Catechin: 181µg/mg and Caffeid acid fixed matrices: 163.66µg/mg.
Conclusion: Quercetin is the most suitable candidate for heart valve crosslinking and could be used as alternative for glutaraldehyde. Whether, Quercetin allows for autologous cell repopulation in order to create a viable tissue engineered heart valve still needs to be investigated.