Tissue-Engineered Heart Valve with a Tubular Leaflet Design for Minimally Invasive Transcatheter Implantation

Abstract

Transcatheter aortic valve implantation of (nonviable) bioprosthetic valves has been proven a valid alternative to conventional surgical implantation in patients at high or prohibitive mortality risk. In this study we present the in vitro proof-of-principle of a newly developed tissue-engineered heart valve for minimally invasive implantation, with the ultimate aim of adding the unique advantages of a living tissue with regeneration capabilities to the continuously developing transcatheter technologies. The tube-in-stent is a fibrin-based tissue-engineered valve with a tubular leaflet design. It consists of a tubular construct sewn into a self-expandable nitinol stent at three commissural attachment points and along a circumferential line so that it forms three coaptating leaflets by collapsing under diastolic back pressure. The tubular constructs were molded with fibrin and human umbilical vein cells. After 3 weeks of conditioning in a bioreactor, the valves were fully functional with unobstructed opening (systolic phase) and complete closure (diastolic phase). Tissue analysis showed a homogeneous cell distribution throughout the valve's thickness and deposition of collagen types I and III oriented along the longitudinal direction. Immunohistochemical staining against CD31 and scanning electron microscopy revealed a confluent endothelial cell layer on the surface of the valves. After harvesting, the valves underwent crimping for 20 min to simulate the catheter-based delivery. This procedure did not affect the valvular functionality in terms of orifice area during systole and complete closure during diastole. No influence on the extracellular matrix organization, as assessed by immunohistochemistry, nor on the mechanical properties was observed. These results show the potential of combining tissue engineering and minimally invasive implantation technology to obtain a living heart valve with a simple and robust tubular design for transcatheter delivery. The effect of the in vivo remodeling on the functionality of the tube-in-stent valve remains to be tested.

Pediatric tubular pulmonary heart valve from decellularized engineered tissue tubes

“…More recently, TEHVs with a tubular leaflet design have been explored that do not rely on complex molds. To date, these tubular TEHVs have all used a single tube – attached to a stent, frame, or within an inert conduit – to generate a valve-like action [13,15,20]. Our group has previously reported a tubular TEHV using a single tube, generated by entrapping fibroblasts in a sacrificial fibrin gel, onto a PEEK frame [21].…”

The Heart and Great Vessels

“…Another important advancement in TEHV research is the development of catheter-based delivery systems for valve implantation (Schmidt et al 2010; Moreira et al 2015). Tissue-engineered valves can be loaded onto stents and inserted transapically for deployment into the pulmonary (Weber et al 2013; Driessen-Mol et al 2014; Schlegel et al 2015) or aortic (Emmert et al 2012) position.…”

Multi-scale modelling of textile reinforced artificial tubular aortic heart valves

“…1 Fabrication of the tube-in-stent valve. From left to right: tubular construct after 1 week of static cultivation still fixed at the silicone connectors, after release from the silicone connectors and placed into the stent, after suturing at the three commissure points and at the base of the tubular construct circumferentially (annulus) [11] valves are produced by using fibrin gel as a cell carrier embedding vascular cells isolated from human umbilical cord veins and a tubular knitted textile structure as a co-scaffold [11]. Initially, the knitted polyethylene terephthalate (PET) mesh is embedded into the fibrin gel containing the cells.…”