Tissue heart valves are an essential component of the surgical armamentarium used to manage severe valvular heart disease. Nevertheless, durability limitations stemming from both calcific and noncalcific tissue deterioration significantly inhibit more widespread tissue valve success andthereby use (169). In each type of bioprosthesis, the observed pathology relates to key differences between the valve substitute and a natural living valve: 1) The cells of the bioprosthesis are no longer viable andthere are no scavenging or remodeling procedures on cellular level; 2) The collagenous valve skeleton is chemically and mechanically altered byvalve preparation, handling, tissue treatments and implantation; 3) Theresidual matrix is not or only limited repopulated by recipient connective tissue or endothelial cells; 4) The fragments of the nonviable donor cells remaining in the valve represent the preferred loci for calcification.In bioprosthetic heart valves, not only the cusps but also the aortic wall portion is prone to calcification. Stentless valves offer many of the theoretical advantages of homografts such as superior hemodynamic performance and enhanced durability, particularly when inserted as a full root. Many of the possible advantages depend on the maintained flexibilityof the aortic wall portion. Calcification of the aortic wall will adversely affect the long-term performance of a stentless prosthesis and it is highly likely that this will limit their durability to a similar time span as their stented couterparts. The level of calcification can even be greater and more likely to cause clinical problems through stiffening,embolism and/or protrusion into the lumen of calcific masses.Experimental animal models are able to mimic clinically observed calcification patterns. The model of pulmonary valve replacement in growing sheep is ideal to study the behaviour and calcification potential of a stentless prosthesis. The simplified jugular vein model is able to produce adequate amounts of aortic wall calcification within short time frames. Subcutaneous rat models can be used as a screening tool, but results will always need validation in larger animals.Within the available models, porcine aortic wall calcification is initiated in cells and cellular remnants. None of the currently available antimineralization treatments is able to prevent wall calcification in stentless grafts. Treatments directed towards the prevention of elastin-based tissue mineralization perform poor.Preventive strategies directed against wall calcification will have to deal with the remaining cell fraction in their prostheses, if not mineralization is likely to occur despite chemical treatment. Acellularizationis an option, but additional tissue fixation other then glutaraldehyde is required. Photo-oxidized porcine tissue or tissue from bovine origin perform better in calcification potential but mechanical stability and stress-resistance are still in doubt.