In vivo and in vitro models of calcification in porcine aortic valve cusps

Both in vivo and in vitro models have been developed to study the initiation and progression of dystrophic calcification of bioprosthetic heart valves. Circulatory in vivo models have proven to be the most predictive of the success of a new valve designs or anticalcification schemes; however, these experiments are time consuming and expensive. An appealing alternative to circulatory implantation is the sub-cutaneous rat implantation model. This model is inexpensive and calcification occurs rapidly. Recent studies have shown, however, that some anticalcification methods work well in the subcutaneous model but are ineffective in the circulatory model. In vitro models would provide the most convenient method for testing new anticalcification strategies but, to date, no in vitro test system has been developed which produces calcification of rates and with morphology comparable with that in vivo models. We have also studied the effects of collagen damage and cell extraction on the calcification of porcine aortic valve cusps both in vitro and in the subcutaneous rat model, and found significant differences in the patterns of mineralization. The objectives of this paper therefore are to compare and contrast the different experimental protocols and procedures reported in the literature to better define the effects of different model systems on the calcification process.