Bioprosthesis Dysfunction
Biological heart valves consist of fixed or decellularized human or animal (usually porcine or bovine) tissue, attached or not to a stent (without a stent in the stentless prosthesis) and a sewing ring (without sewing ring in the sutureless prosthesis). Structural dysfunction is a logical and expected consequence of the chemical, mechanical and immunological processes that occur during fixation, fabrication and implantation.
Beside all the technological development in the past decades, bioprosthesis only replicate native heart valve structure. In bioprosthesis, 1) the cusps are constituted by subendothelial connective tissue; 2) the cusps are locked in a static geometry and 3) have nonviable cells due to the fixation and crosslinking processes (21, 22). They lack the functional capacities of heart valves and the preservation techniques severely decrease functional activity of the natural matrix (17). Thus, they are not able to maintain the normal remodeling processes.
Over the past 50 years, glutaraldehyde (Glut) has been the most used chemical and is nowadays widely used to preserve and stabilize biological prosthetic tissues. Glut is an aldehyde with fixative and preservative functions (43), firstly introduced in 1963 by Sabatini et al as a fixative for electronic microscopy. Glut is responsible for the chemical crosslinking (creation of covalent chemical bonds to stabilize tissues and terminate any ongoing biochemical reactions), enhancing material stability and reducing antigenicity (29, 30). However, Glut is also partly responsible for prosthesis dysfunction, directly because of its toxicity and indirectly through the processes described ahead.
Valve degeneration is a multifactorial process, including chemical, mechanical and immunological factors (Figure 2). The contribution of each mechanism remains poorly understood, but represents an active and attractive field of investigation. The common endpoint of all these processes is calcification and degradation, culminating in the failure of the structure with bioprosthetic dysfunction.