Scaffolds for heart valve tissue engineering must function immediately after implantation but also need to tolerate cell infiltration and gradual remodeling. We hypothesized that moderately cross-linked collagen scaffolds would fulfill these requirements. To test our hypothesis, scaffolds prepared from decellularized porcine pericardium were treated with penta-galloyl glucose (PGG), a collagen-binding polyphenol, and tested for biodegradation, biaxial mechanical properties, and in vivo biocompatibility. For controls, we used un-cross-linked scaffolds and glutaraldehyde-treated scaffolds. Results confirmed complete pericardium decellularization and the ability of scaffolds to encourage fibroblast chemotaxis and to aid in creation of anatomically correct valve-shaped constructs. Glutaraldehyde cross-linking fully stabilized collagen but did not allow for tissue remodeling and calcified when implanted subdermally in rats. PGG-treated collagen was initially resistant to collagenase and then degraded gradually, indicating partial stabilization. Moreover, PGG-treated pericardium exhibited excellent biaxial mechanical properties, did not calcify in vivo, and supported infiltration by host fibroblasts and subsequent matrix remodeling. In conclusion, PGG-treated acellular pericardium is a promising scaffold for heart valve tissue engineering.

Surgical replacement with artificial devices has revolutionised the care of patients with severe valvular diseases. Mechanical valves are very durable, but require long-term anticoagulation. Bioprosthetic heart valves (BHVs), devices manufactured from glutaraldehyde-fixed animal tissues, do not need long-term anticoagulation, but their long-term durability is limited to 15 – 20 years, mainly because of mechanical failure and tissue calcification. Although mechanisms of BHV calcification are not fully understood, major determinants are glutaraldehyde fixation, presence of devitalised cells and alteration of specific extracellular matrix components. Treatments targeted at the prevention of calcification include those that target neutralisation of the effects of glutaraldehyde, removal of cells, and modifications of matrix components. Several existing calcification-prevention treatments are in clinical use at present, and there are excellent mid-term clinical follow-up reports available. The purpose of this ...