DEVELOPMENT OF TISSUE ENGINEERED XENOGRAFTS

Heart valve diseases have a significant high mortality, and the valve replacement using glutaraldehyde crosslinked xenografts is one of the main curing techniques. But its application is limited due to poor durability, calcification of the valves and immunogenic reactions. Sub-optimal clinical outcomes after implantation of animal-derived tissue matrices may be attributed to the nature of the processing of the material or to an immune response elicited in response to xenogeneic epitopes [galactose-a-(1,3)-galactose terminal disaccharide (a-Gal)]. Tissue-engineered or decellularized xenografts and homografts have already been implanted in humans or are currently approaching the clinical setting. However, the success of tissue-engineering procedures depends on the choice of an appropriate biomaterial. Decellularized xenogenic tissue potentially combines the structural composition of the targeted tissue with a reduced risk of graft rejection or disease transmission. In this study, we will test the effectiveness of currently available decellularization methods based on TRITON-X, sodium dodecyl sulfate (SDS), and trypsin. After identifying the most effective decellularization method, the tissue will undergo different novel crosslinking reagents and subsequently the capacity for reseeding with endothelial cells will be studied.