Vascular implants – new aspects for in situ tissue engineering

Conventional synthetic vascular grafts require ongoing anticoagulation, and autologous venous grafts are often not available in elderly patients. This review highlights the development of bioartificial vessels replacing brain-dead donor- or animal-deriving vessels with ongoing immune reactivity. The vision for such bio-hybrids exists in a combination of biodegradable scaffolds and seeding with immune-neutral cells, and here different cells sources such as autologous progenitor cells or stem cells are relevant. This kind of in situ tissue engineering depends on a suitable bioreactor system with elaborate monitoring systems, three-dimensional (3D) visualization and a potential of cell conditioning into the direction of the targeted vascular cell phenotype. Necessary bioreactor tools for dynamic and pulsatile cultivation are described. In addition, a concept for design of vasa vasorum is outlined, that is needed for sustainable nutrition of the wall structure in large caliber vessels. For scaffold design and cell adhesion additives, different materials and technologies are discussed. 3D printing is introduced as a relatively new field with promising prospects, for example, to create complex geometries or micro-structured surfaces for optimal cell adhesion and ingrowth in a standardized and custom designed procedure. Summarizing, a bio-hybrid vascular prosthesis from a controlled biotechnological process is thus coming more and more into view. It has the potential to withstand strict approval requirements applied for advanced therapy medicinal products

A promising protocol for the endothelialization of vascular grafts in an instrumented rotating bioreactor towards clinical application

Pre-endothelialization of a tissue-engineered vascular graft before implantation aims to prevent thrombosis and immunoreactions. This work demonstrates a standardized cultivation process to build a confluent monolayer with human aortal endothelial cells on xenogenous scaffolds. Pre-tested dynamic cultivation conditions in flow slides with pulsatile flow (1 Hz) representing arterial wall conditions were transferred to a newly designed multi-featured rotational bioreactor system. The medium was thickened with 1% methyl cellulose simulating a non-Newtonian fluid comparable to blood. Computational fluid dynamics was used to estimate the optimal volume flow and medium distribution inside the bioreactor chamber for defined wall-near shear stress levels. Flow measurements were performed during cultivation for constant monitoring of the process. Three decellularized porcine arteries were seeded and cultivated in the bioreactor over six days. 1% MC turned out to be the optimal percentage to achieve shear stress values ranging up to 10 dyn/cm2. Vascular endothelial cells formed a continuous monolayer with significant cell alignment in the direction of flow. The presented cultivation protocol in the bioreactor system thus displays a promising template for graft endothelialization and cultivation. Therefore, establishing a key step for future tissue-engineered vascular graft development with a view towards clinical application