Orthotopic Replacement of Aortic Heart Valves with Tissue-Engineered Grafts

Abstract

Tissue-engineered AV based on decellularized valve allografts satisfy short-term requirements of the systemic circulation in sheep. Although results of long-term experiments are pending, the lack of degenerative traits thus far, makes these grafts a promising alternative for future aortic heart valve surgery.

Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

“…Heart valve tissue engineering (HVTE), the science of combining scaffolds, cells and stimuli has the potential to revolutionize the field of valve surgery by providing functional, durable, and viable valves. To date, several approaches have been tested using synthetic and natural scaffolds and a variety of cells and bioreactors, but overall most approaches have not been successful on the long term when tested in animals or human patients as pulmonary or aortic implants (2,(4)(5)(6). At this stage of research, there are numerous aspects which still need to be studied, optimized or tested before HVTE can make an impact on clinical applications.…”

“…At this stage of research, there are numerous aspects which still need to be studied, optimized or tested before HVTE can make an impact on clinical applications. For example, it is not yet known what the ideal scaffold properties are and whether it should be rapidly degradable, slowly degradable or not degradable at all (2,(4)(5)(6)20). Other topics of research are cell sourcing, propagation, whether in vitro differentiation or in vitro mechanical pre-conditioning is needed before implantation, seeding methods, and optimal number of seeded cells.…”

“…Moreover, it is well known that acellular tissues, if fully decellularized, are not immunogenic, because collagen and elastin are two proteins which have been preserved throughout evolution and thus are not different among species. For this reason, more than 1 million acellular tissues and collagen scaffolds in liquid or solid form have already been implanted in humans without any signs of immunologic rejection (6,12). Therefore, acellular valves are not expected to activate the immune system (6).…”

“…This has been recognized as the FDA-recommended animal model for testing new designs of mechanical valves, tissue-based bioprosthetic valves, cryopreserved homografts and biohybrid devices (6,20,(23)(24)(25)(26)(27)(28). Although not initially developed for tissue engineering, sheep implantation continues to be the animal model of choice for testing of acellular valve scaffolds (29)(30)(31)(32)(33)(34).…”

“…An ideal tissue engineered heart valve (TEHV) should encompass several characteristics: good hemodynamics, appropriate valve geometry, high durability, non-immunogenicity, non-inflammatory, non-thrombogenic and non-calcifying (1,3). Additionally, for young patients, it should have the ability to grow and adapt with the patient's somatic growth (2,(4)(5)(6).…”