Autologous bioengineered heart valves: An update

Abstract

Current valve replacement options are limited in their capacity to grow, self-repair, and remodel. Therefore, no ideal valve replacement option exists for the pediatric or young adult population. Researchers have thus turned to tissue engineering, especially with the use of autologous cell sources in order to avoid issues of immunogenicity. The current paradigm uses a scaffold seeded with autologous cells, sometimes expanded and stressed in vitro, prior to implantation. Each step of this process is reviewed here. Biodegradable polymer scaffolds are an attractive option because they can be readily manufactured and provide an off-the-shelf product. However, cell attachment, in vivo degradation performance, and biomechanics are just some of the hurdles to overcome. An alternative to synthetic polymer scaffolds is to decellularize a natural valve which already has the desired structure and functionality. Decellularization reduces immunogenicity and rejection and can be applied to both allografts (human cadaveric) and xenografts (typically porcine). Various decellularization protocols have been tried with successes and failures. Cells that have been then seeded onto the scaffolds include vascular endothelial cells, myofibroblasts, circulating endothelial progenitor cells, and bone-marrow derived stem cells. Bioreactors are becoming increasingly complex with dynamic conditions exerting multiple shear forces on the cells. Meanwhile there is also a movement towards simpler, more practical, hospital-friendly bioreactors. A small series of clinical applications have already been published. Alternative delivery routes, including via transcatheter delivery systems are currently under investigation. Each step in the process of producing autologous bioengineered heart valves has seen growth in the last two decades and gradually researchers are working towards a viable tissue engineered alternative to current prosthetic valves.