Tubular Heart Valves from Decellularized Engineered Tissue

Abstract

A novel tissue-engineered heart valve (TEHV) was fabricated from a decellularized tissue tube mounted on a frame with three struts, which upon back-pressure cause the tube to collapse into three coapting “leaflets”. The tissue was completely biological, fabricated from ovine fibroblasts dispersed within a fibrin gel, compacted into a circumferentially-aligned tube on a mandrel, and matured using a bioreactor system that applied cyclic distension. Following decellularization, the resulting tissue possessed tensile mechanical properties, mechanical anisotropy, and collagen content that were comparable to native pulmonary valve leaflets. When mounted on a custom frame and tested within a pulse duplicator system, the tubular TEHV displayed excellent function under both aortic and pulmonary conditions, with minimal regurgitant fractions and transvalvular pressure gradients at peak systole, as well as well as effective orifice areas exceeding those of current commercially available valve replacements. Short-term fatigue tests of one million cycles with pulmonary pressure gradients was conducted without significant change in mechanical properties and no observable macroscopic tissue deterioration. This study presents an attractive potential alternative to current tissue valve replacements due to its avoidance of chemical fixation and utilization of a tissue conducive to recellularization by host cell infiltration.

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

“…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).…”

Building New Hearts: A Review of Trends in Cardiac Tissue Engineering

“…Syedain et al (27) fabricated valves by molding fibrin gel with encapsulated fibroblasts into a tubular shape, culturing the tube within a bioreactor to mimic physiological strain, and then decellularizing the generated tissue. The resulting valves had mechanical properties and anisotropy similar to those of native pulmonary valves.…”

Mechanisms of Cardiac Valve Failure and the Development of Tissue Engineered Heart Valves

“…Syedain et al created a scaffold utilizing fibroblasts in a fibrin gel and then decellularizing the resulting tissue to create a decellularized tube. This tube is placed over a trident stent and the result is a functional valve with short term function in a sheep pulmonary artery [47]. A similar approach was taken by Dijkman et al, who utilized biodegradable polyglycolic mesh leaflets seeded with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and then decellularized the valves.…”