Tissue-Engineered Fibrin-Based Heart Valve with a Tubular Leaflet Design

Abstract

The general approach in heart valve tissue engineering is to mimic the shape of the native valve in the attempt to recreate the natural haemodynamics. In this article, we report the fabrication of the first tissue-engineered heart valve (TEHV) based on a tubular leaflet design, where the function of the leaflets of semilunar heart valves is performed by a simple tubular construct sutured along a circumferential line at the root and at three single points at the sinotubular junction. The tubular design is a recent development in pericardial (nonviable) bioprostheses, which has attracted interest because of the simplicity of the construction and the reliability of the implantation technique. Here we push the potential of the concept further from the fabrication and material point of view to realize the tube-in-tube valve: an autologous, living HV with remodelling and growing capability, physiological haemocompatibility, simple to construct and fast to implant. We developed two different fabrication/conditioning procedures and produced fibrin-based constructs embedding cells from the ovine umbilical cord artery according to the two different approaches. Tissue formation was confirmed by histology and immunohistology. The design of the tube-in-tube foresees the possibility of using a textile coscaffold (here demonstrated with a warp-knitted mesh) to achieve enhanced mechanical properties in vision of implantation in the aortic position. The tube-in-tube represents an attractive alternative to the conventional design of TEHVs aiming at reproducing the valvular geometry.

Imaging Strategies for Tissue Engineering Applications

“…Specifically for tissue engineering applications, probes targeted to a v b 3 , a biological marker of angiogenesis, have been developed for noninvasive imaging of angiogenesis. 35,36 One example of these biodegradable probes, developed by Almutairi et al, consists of eight branches functionalized with the radiohalogen 76 Br and the targeting peptide RGD at the ends of polymer chains. 36 The nanoprobes showed high specific uptake in angiogenic muscles in an in vivo murine hindlimb ischemia model, as shown in Figure 4B.…”

“…75 Doppler ultrasound imaging with injection of air bubbles was applied to demonstrate correct functioning of a tissue-engineered heart valve based on a tubular leaflet design and efficient replacement of the volume in a flow-loop bioreactor. 76 Moreover, microbubbles were injected into extracellular matrix scaffolds to ultrasonically assess flow rates, 3D vessel network architecture, characterization of microvessel volumes and sizes, and delineation of matrix from vascular circuits, as shown in Figure 6C. 77 …”

Effect of reinforcement volume fraction and orientation on a hybrid tissue engineered aortic heart valve with a tubular leaflet design

“…The fibers were chosen based on the textile reinforcement used in a heart valve by Weber et al [6]. This study used polyethylene terephthalate (PET) fibers with 17 µm diameter, 24 fibers per yarn, and the yarns had a spacing of approximately 1.6 mm (see Fig.…”

“…Recently, we introduced a simplified design as an alternative to the classical one: a simple tissue-engineered tubular construct is sutured orthotopically in the aortic or pulmonary root at three sinotubular commissural points, and along a circumferential line at the annulus [6]. The tubular construct collapses inwardly under diastolic back pressure, closing the valvular conduit and opens again during systole (Fig.…”

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

“…Different kinds of TEHVs are in development by various groups. One such TEHVs is being developed by the group at the Applied Medical Engineering Institute of RWTH Aachen University [6], as shown in Fig. 1.…”