Abstract
Heart valve disease contributes to cardiovascular disease-associated death. Bioprosthetic heart valves have emerged as a preferred option for heart valve replacement due to their superior hemodynamic performance and reduced need for lifelong anticoagulation. However, their long-term durability is compromised by calcification, immunogenicity, and structural degeneration, primarily due to glutaraldehyde fixation and residual xenogeneic antigens. This review highlights recent advances in biomaterial optimization, with an emphasis on decellularization and cross-linking strategies aimed at improving the mechanical stability and biocompatibility of bioprosthetic heart valves. The effectiveness and limitations of various decellularization agents, including nonionic, ionic, and amphoteric detergents, are critically evaluated, alongside novel cross-linking reagents such as ribose, genipin, and polyphenols. Furthermore, the development of polymeric heart valves and nanocomposite materials is also explored as a means to address the limitations of conventional mechanical and bioprosthetic valves. Emerging strategies involving gene-editing technologies, stem cell therapies, and tissue engineering hold considerable promise for the development of next-generation, patient-specific, and immunotolerant heart valve prostheses. Collectively, these innovations are driving a paradigm shift toward long-lasting, bioactive, and regenerative heart valve replacements.