Tissue‐Engineered Fibrin‐Based Heart Valve with Bio‐Inspired Textile Reinforcement

Abstract

The mechanical properties of tissue-engineered heart valves still need to be improved to enable their implantation in the systemic circulation. The aim of this study is to develop a tissue-engineered valve for the aortic position - the BioTexValve - by exploiting a bio-inspired composite textile scaffold to confer native-like mechanical strength and anisotropy to the leaflets. This is achieved by multifilament fibers arranged similarly to the collagen bundles in the native aortic leaflet, fixed by a thin electrospun layer directly deposited on the pattern. The textile-based leaflets are positioned into a 3D mould where the components to form a fibrin gel containing human vascular smooth muscle cells are introduced. Upon fibrin polymerization, a complete valve is obtained. After 21 d of maturation by static and dynamic stimulation in a custom-made bioreactor, the valve shows excellent functionality under aortic pressure and flow conditions, as demonstrated by hydrodynamic tests performed according to ISO standards in a mock circulation system. The leaflets possess remarkable burst strength (1086 mmHg) while remaining pliable; pronounced extracellular matrix production is revealed by immunohistochemistry and biochemical assay. This study demonstrates the potential of bio-inspired textile-reinforcement for the fabrication of functional tissue-engineered heart valves for the aortic position.

JetValve: Rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement

“…As a result, transvalvular pressure gradients of <2 mmHg were observed in vivo which is equivalent to recently published human and ovine tissue engineered heart valve (<5 mmHg) [31, 53]. However, in vitro pulse duplicator testing did reveal a regurgitant fraction of approximately 30% which is above ISO standards of similarly sized heart valves [52]. These data did not appear, though, to fully predict JetValve functionality in vivo where rapid and complete leaflet coaptation and minimal closing jet were observed with echo/doppler imaging.…”

“…During this period, P4HB/Gelatin content remained within compositional range for mimicking the measured native tissue stiffness values. This length of hydrated shelf life is comparable to recent fiber/gel valvular scaffold composites [52] and is well in excess of the time required for pre-implantation procedures: on the order of hours for stent fixation, crimping, and surgical delivery preparation.…”

“…ISO) for the assessment of tissue engineered heart valve functional performance [52, 53], little work has been done to establish industrial-style quality control standards for tissue engineering manufacturing processes and products [54]. Therefore the structural, mechanical, and compositional scaffold design parameters discussed above were measured and evaluated for each JetValve prepared for implantation as a factor of safety for the animal models used.…”

“…Growth factors associated with development such as transforming growth factor-β1 (TGF-β1), bone morphogenic proteins (BMPs), and/or platelet-derived growth factors (PDGFs) may be incorporated into scaffolds to elicit endothelial-to-mesenchymal transformation (EMT), for example, in order to populate and remodel the scaffold [55, 62, 63]. Additionally, recently reported hybrid-manufacturing techniques for the production of more complex, tri-layered scaffolds have been developed in an effort to better mimic the anisotropic, stratified structure of the valvular ECM for optimal hemodynamic performance and tissue regeneration [52, 64–66]. The JetValve production platform is amenable to fabrication of similarly layered scaffolds while maintaining industrial-like scaffold production rates [67–69] due to its additive nature.…”

Biologically Inspired Scaffolds for Heart Valve Tissue Engineering via Melt Electrowriting

“…Next, we evaluated the scaffolds' capability to support human umbilical cord vein smooth muscle cells (HUVSMCs) growth, proliferation, and extracellular matrix deposition. We chose these cells as they have been shown to be appropriate for cardiovascular tissue engineering and are clinically‐relevant for the pediatric population, which could greatly benefit from TEHV by avoiding the repeated surgeries to accommodate somatic growth. HUVSMCs were seeded in two different configurations: i) direct seeding onto the surface of the scaffold and ii) encapsulated in fibrin and composited in a molding process resulting in the complete embedding of the scaffold in a cell‐laden fibrin gel.…”