Research Projects

Hybrid Tissue-Engineered Heart Valve

Heart valve disease remains to be a significant health problem worldwide. It refers to any dysfunction or disease process of one or more of the heart.s four valves and is associated with higher rates among the elderly people. It can be congenital or acquired during one.s lifetime. Two phenomena are commonly observed; valvular stenosis (insufficient blood flow due to the narrowed valve opening) and valvular regurgitation (insufficiency, incompetence, or leaky valve). Currently, no medication can cure heart valve disease, but replacement or repair markedly reduces the morbidity and mortality associated with the disease. Current heart valve replacement options are limited to mechanical and bioprosthetic heart valves that are either thrombogenic or have limited durability, and thus a better solution is needed. Tissue engineering is trying to resolve these issues by creating native-like structures through in vitro or in situ fabrication methods. However, these valves are unable to adjust to the dynamic loads of the ventricles. Thicker and/or stiffer tissues and, in some cases, leaflet retraction have been observed following implantation of these valves.

Hybrid heart valve at various stages of development. Nitinol structure along with (A) smooth muscle, (B) fibroblast/myofibroblast, and (C) endothelial cells, all encapsulated in collagen as the first, second, and third layers, respectively.

To overcome these limitations, we are working toward development and testing the first patient-specific hybrid heart valve with self-regenerating capacity, and potential for lifelong durability. The hybrid valves. leaflets are made of an extra thin nitinol mesh core as a permanent scaffold tightly enclosed by an in-vitro cultured tissue layer composed of three different cell types; smooth muscle cells, fibroblast/myofibroblast, and endothelial layer. Nitinol was utilized due to its superelastic nature in addition to its superior strain controlled fatigue performance. The mesh pattern was designed in a way to have minimum effect on tissue remodeling. The enclosing tissue was engineered as a tri-layered structure with cellular types and densities resembling native ventricularis, fibrosa, and spongiosa. Due to these, we believe this model can address the issues associated with tissue engineered heart valves with degradable scaffolds. This hybrid valve promises the long-term durability of mechanical valves with the improved biocompatibility and hemodynamics of bioprosthetic heart valves. More information can be found here.

Qualitative histologic assays performed on the statically and dynamically conditioned groups. H&E stain representing a spongy structure for (A) static group versus (B) dense composition for dynamically conditioned leaflets. (C) Stimulated raman scattering staining shows that the mesh is completely enclosed within the tissue. (D) Light Green staining demonstrates a fibrous structure with a uniform cellularity throughout the leaflets.

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