Development of Tissue Engineered Heart Valves for Percutaneous Transcatheter Delivery in a Fetal Ovine Model

Figures

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  Figure 1. Manufacturing of Fully Degradable Fetal Tissue-Engineered Heart Valve (A) Schematic of valve design. (B) A tube of electrospun polycaprolactone (PCL) is attached to a biodegradable zinc-aluminum stent with circumferential sutures, and 3 sutures used to create the valve leaflets. The completed tissue-engineered heart valve is shown (i) in side view as well as in the valve (ii) open and (iii) closed positions. Scale bar = 2 mm.

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  Figure 2. Implantation of TEHV (A) The tissue-engineered heart valve (TEHV) was crimped with a manual crimper onto (B) a balloon catheter and was deployed by inflation of the balloon. Scale bar = 2 mm. Implantation of the TEHV was performed through percutaneous transapical approach via (C) a 17-gauge (G) trocar guided by (D) ultrasound (US) into the pulmonary annulus. (E) The fetal lamb was born at term. PV = pulmonary valve; RV = right ventricle.

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  Figure 3. Mechanical Analysis of Tissue-Engineered Heart Valve (A) En face imaging during the cardiac cycle from acceleration, peak systole, deceleration, and diastole. Full video available in Video 1. (B) Quantification of flow rate, pulmonary pressure, and pressure gradient measured within the flow duplicator. (C) Biaxial mechanical testing using an array of tensile to shear protocols demonstrated that the polycaprolactone (PCL) showed anisotropy toward the primary (circumferential) direction. Representative mechanical testing results shown. ES = equibiaxial strain; F = deformation; IP = in-plane axial strain; MAX = maximum axial and shear strain; P = stress; PD = preferred direction; SS = simple shear (only in one direction); SSA = simple shear all (in both directions); XD = cross-preferred direction.

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  Online Video 1

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  Figure 4. In Vitro Degradation of Tissue-Engineered Heart Valve PCL (A) Electrospun polycaprolactone (PCL) sheets were subjected to accelerated degradation in sodium hydroxide, demonstrating an initial period of minor microstructural changes, followed by rapid structural collapse. (B) Mass loss over the accelerated degradation time showed a similar profile of minor and then steady mass loss over time. (C) Molecular analysis of the degraded samples demonstrated rapid changes in molecular size (Mn), molecular weight (Mw) and polydispersity index (PDI) at early time points, followed by steady decreases at later times.

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  Figure 5. Successful Delivery of Tissue-Engineered Heart Valve in the Fetal Pulmonary Annulus Following (A) successful deployment of a tissue-engineered heart valve (red circle) into the pulmonary annulus of a fetal sheep, (B) laminar flow was detected through the TEHV (yellow arrow) on ultrasound. TEHV = tissue-engineered heart valve.