Design and fabrication of biomimetic scaffolds With soft tissue-like mechanical properties for heart valve tissue engineering

Valvular heart disease is the third leading contributor to cardiovascular disease resulting in more than 5 million deaths annually. Heart Valve Tissue Engineering (HVTE) aims to provide mechanically stable valves that support tissue growth and remodelling to replace synthetic and non-bioactive prosthetics which are incapable of these features. In an effort to fabricate biodegradable and mechanically advanced scaffold for HVTE, we utilized a novel fabrication technology called Melt Electrospinning Writing (MEW) which combines the principles of both electrospinning and additive biomanufacturing to produce highly organised fibrous constructs with micrometric features. We manufactured medical-grade poly ε-caprolactone (PCL) constructs that mimics the wavy architecture of collagen fibres found in native leaflets and characterised their microstructure, mechanical properties and cell to scaffold interaction.

MEW scaffolds showed highly controlled architectures, with highly controlled fibre stacking and minimal fibre bridging defects. Results for all groups displayed a J-shaped stress/strain curve typical of a native aortic valve leaflet. The linear elastic modulus, tangent modulus, young’s modulus and ultimate tensile stress were modulated by altering the fibre spacing and the number of deposited layers while the strain at which the maximum stress occurs was tuned from 20 to 100% by controlling the amplitude of helically patterned fibres. Moreover, the anisotropic ratio was curbed from 2 to 20 times by altering fibre spacing in the radial direction. Further mechanical testing displayed outstanding fatigue, stress relaxation and hysteresis properties of the scaffolds under cyclic loading conditions.

Finally, human umbilical vein smooth muscle cells (HUVSMCs) were seeded on the scaffold either directly or encapsulated in fibrin gel. High cell viability, infiltration and deposition of collagen I, III after 7 and 14 days of static culture was observed. The phenotype of the cells was characterised by immunohistochemistry, showing high expression of alpha-SMC and vimentin and no expression of Calponin.

Altogether, these results demonstrate the great potential of MEW and a biomimetic design strategy for the manufacture of scaffolds for HVTE applications.