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Vascular in vitro tissue engineering has seen a constant evolution from first in vitro engineered constructs to fully functional, growing replacements in large animal in vivo models. The rise of the induced pluripotent stem cells (iPSCs) technology had a major impact on the entire field providing a promising cell source for tissue engineering and regenerative medicine applications. In particular, the differentiation capacities into all cellular types of the human body combined with unlimited scale-up potential made iPSC a highly attractive cell source. This chapter will focus on recent advances in the field of vascular tissue engineering and elaborate potential cell sources and scaffold materials with a particular focus on the use of iPSC. Additionally, iPSC reprogramming strategies and differentiation methods to obtain mature cells with vascular phenotypes will be discussed.

Background The donkey pericardium is considered a good candidate to manufacture percutaneous heart valves based upon its thinness, low cellularity and undulating collagen bundles and laminates. Decellularization represents an avenue worth exploring, should its superiority to glutaraldehyde-treated pericardium be demonstrated. Materials and methods Donkey pericardium was divided into two groups: regular glutaraldehyde fixation and mild decellularization. The treated pericardia were observed using scanning electron microscopy, histology and transmission electron microscopy. Tensile tests were performed along the axial and perpendicular directions, with the data fitted into both the Gasser–Ogden–Holzapfel (GOH) material model and the Fung’s anisotropic one. Results The microstructures of the pericardia processed by the two protocols were similar, showing collagen bundles and laminates free of flaws. The decellularization eliminated most of the cells, however leaving the structure somehow compressed. The collagen filaments in bundles were slightly blurry. The anisotropy rates of the non-decellularized specimens were almost identical to the decellularized ones. The decellularized pericardium appeared stiffer. Conclusion The decellularization proved to be effective. However, it makes the tissue stiffer, which may lead to higher shear concentration during cardiac cycles and reduce its wavy microstructure. Therefore, it appears premature to select decellularized donkey pericardium to manufacture heart valves.

Heart valve tissue engineering based on decellularized xenogenic or allogenic starter matrices has shown promising first clinical results. However, the availability of healthy homologous donor valves is limited and xenogenic materials are associated with infectious and immunologic risks. To address such limitations, biodegradable synthetic materials have been successfully used for the creation of living autologous tissue-engineered heart valves (TEHVs) invitro. Since these classical tissue engineering technologies necessitate substantial infrastructure and logistics, we recently introduced decellularized TEHVs (dTEHVs), based on biodegradable synthetic materials and vascular-derived cells, and successfully created a potential off-the-shelf starter matrix for guided tissue regeneration. Here, we investigate the host repopulation capacity of such dTEHVs in a non-human primate model with up to 8 weeks follow-up. After minimally invasive delivery into the orthotopic pulmonary position, dTEHVs revealed mobile and thin leaflets after 8 weeks of follow-up. Furthermore, mild-moderate valvular insufficiency and relative leaflet shortening were detected. However, in comparison to the decellularized human native heart valve control - representing currently used homografts - dTEHVs showed remarkable rapid cellular repopulation. Given this substantial in situ remodeling capacity, these results suggest that human cell-derived bioengineered decellularized materials represent a promising and clinically relevant starter matrix for heart valve tissue engineering. These biomaterials may ultimately overcome the limitations of currently used valve replacements by providing homologous, non-immunogenic, off-the-shelf replacement constructs. © 2013 Elsevier Ltd.