Different types of synthetic scaffolds are used for tissue engineering of heart valves. Tissue-engineered heart valves (TEHV), based on a rapid degrading polyglycolic acid (PGA) scaffold coated with poly-4-hydroxybutyrate (P4HB) and seeded with vascular derived cells, have shown promising in-vivo results. However, a major drawback of these TEHV is compaction and retraction of the leaflets causing regurgitation. It is hypothesized that this is a result of traction forces exerted by the cells, combined with an imbalance of the formed tissue and loss of mechanical integrity of the scaffold due to degradation. The aim of this study is to evaluate alternative approaches to overcome the compaction and retraction of TEHV without compromising on tissue composition and properties. The alternative approaches that are studied here are 1) the use of the slow degrading poly-ε-caprolactone (PCL) scaffold for prolonged mechanical integrity and 2) the use of lower passage vascular cells for enhanced tissue formation. Compaction, tissue formation, cell phenotype and mechanical properties of tissues based on passage 3, 5 and 7 vascular cells in PCL and PGA-P4HB scaffolds are compared. TEHV aim to be designed for humans, but since the ovine model is used to show proof of principle both human and ovine cells were used. Passage 3, 5 and 7 (p3, p5 and p7) human and ovine vascular-derived cells were seeded onto both PGA-P4HB and PCL scaffold strips (n=6 per passage and scaffold material), using fibrin as a cell carrier. After 4 weeks of culture under constrained static conditions, one strip was used for histology. The remaining strips were used for mechanical testing and biochemical assays as indicators for tissue strength and tissue formation, respectively. After 4 weeks, the tissues based on PGA-P4HB showed 50-60% compaction, while PCL-based tissues showed compaction of 0-10%. Cell passage number and species did not influence compaction. Tissue formation was comparable between passage numbers and scaffold materials in ovine while human p5 showed decreased tissue formation in both scaffold materials. Collagen content was increased with decreasing passage numbers in both species and scaffold materials. No differences in cell phenotype between the scaffold materials or cell passage numbers were observed. The Young’s modulus and the ultimate tensile strength of tissues of both species were higher in the lower passage groups of both scaffold groups. This study shows that PCL scaffolds may serve as alternative scaffold material for tissue engineering heart valves with minimal compaction and without compromising on tissue composition and properties. Cells from lower passages showed to improve tissue formation. Reducing cell expansion time will result in faster generation of TEHV, providing a more rapid treatment to patients.


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  • Accepted: 29 May 2012
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