A Bioinspired Mitral Valve: Integrating Melt-electrowritten Scaffolds with a Human Placenta-derived Extracellular Matrix Hydrogel

Abstract

Few implant designs for the mitral valve (MV) respect crucial MV-specific characteristics such as its D-shaped annulus, two asymmetric and anisotropic leaflets, and the chordal apparatus. Following the concept of in situ tissue engineering, we propose a composite MV implant consisting of a mechanically controlling bioinspired microfiber scaffold embedded in a soft human placenta-derived extracellular matrix (hpECM) hydrogel. Seamless macroporous scaffolds were fabricated via melt electrowriting (MEW) and consisted of sinusoidal fiber patterns of polycaprolactone (diameter = 20.9 µm ± 1.6 µm) in the leaflets that transitioned into straight fiber bundles to mimic the chordae. The anisotropic J-shaped stress-strain behavior of the leaflets matching those of the native MV tissue was confirmed via biaxial tensile testing (n = 5). The macropores of the MEW scaffolds were sealed by an hpECM hydrogel via mold casting to provide a balance between bioactivity and mechanical stability. The composite MVs were sutured to a D-shaped annulus and tested in a mock circulatory system. All MVs (n = 3) complied with the requirements set out by ISO 5840, showing an effective orifice area of 2.06 ± 0.06 cm² and a regurgitation fraction of 6.99 ± 1.61 % at 5 L/min and a peak differential pressure of 120 mmHg using a blood mimicking fluid. Our biofabrication strategy leverages controlled microfiber deposition via MEW to form a complex and anatomically relevant scaffold architecture recapitulating some of the key anatomical and biomechanical characteristics of the native MV apparatus with the potential to be remodeled by autologous cells.