Templated Assembly of Silk Fibroin for a Bio-Feedstock-Derived Heart Valve Leaflet

Abstract

Bioprosthetic valves are employed to replace defective heart valves. However, structural degeneration is prevalent in bioprosthetic valves because the heart valve leaflets are exposed to extreme and repetitive cardiovascular pressure. Herein, a silk fibroin-based heart valve leaflet, which executes the physiological role of a heart valve, is developed. To this end, a templated assembly technology is developed. Notably, a physically optimal hierarchical structure for replacing the natural heart valve leaflet is realized by numerous firmly stacked beta-sheet crystals distributed within collective tyrosine-reinforcing amorphous strands. Almost half (46.9%) of the silk fibroin-based heart valve leaflet comprises strongly stacked beta-sheet crystals, leading to a 292% enhancement in stacking strength. The templated assembly results in the entanglement of amorphous strands, upregulating the non-covalent interactions within the tyrosine. Consequently, the strength is enhanced by 1380% compared to native silk fibroin. Moreover, the templated assembly enhances the static and dynamic mechanical properties, thereby delivering a desirable performance for its use in heart valve replacement. Interestingly, the aortic valve composed of silk fibroin-based leaflets does not fail under the cardiovascular pressure of 60-180 mmHg. Furthermore, the valve performance is satisfactory and surmounts the requirements of the industrial standard ISO 5840. Silk fibroin-based heart valve leaflet (SLEAF) is prepared by developing the templated assembly technology. In particular, SLEAF comprises numerous firmly stacked beta-sheet crystals distributed within collective tyrosine-reinforcing amorphous strands. SLEAF presents the mechanical properties desirable for heart valve replacement. SLEAF-based bioprosthetic aortic valve (SLEAF-AV) shows superior durability and valvular performance fulfilling the industrial standard.image