Project Details
Projekt
A bioreactor system for cultivation of bioartificial vascular graft systems - evaluation and optimization of cultivated test structures
Subject Area
Biological Process Engineering
Term
since 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 388094931
The aim of this proposal is to develop a bioreactor system and an optimized manufacturing process for bioartificial vascular grafts. Such tissue-engineered vascular grafts (TEVGs) are to be produced as biohybrids based on a non-immunogenic scaffold structure, if possible. For this purpose, biodegradable scaffold structures from 3D printing are used here, which are colonized with immune-neutral cells and can be exposed in the recipient to further spontaneous colonization by monocytic cells circulating in the bloodstream. Optimal TEVGs as biohybrid structures are biomechanically resilient, seeded with dynamically trained endothelial cells as thromboprophylaxis, and the underlying biodegradable polymer exhibits adequate degradation behavior in vivo. Endothelial colony-forming progenitor cells (ECFCs) that can be isolated from the peripheral bloodstream can be used as human cells. In order to be able to produce bioartificial vascular prostheses with the above quality claim, the functionality of the bioreactor system and the colonization protocol will be further optimized with regard to the development of TEVGs with 3D-printed tubular scaffolds made of biodegradable polymers such as polycaprolactone and polydioxanone. To this end, the present bioreactor will first be further technically developed towards effortlessly controllable hemodynamics and a homogeneous flow profile with definable near-wall shear stress regions will be evaluated by means of simulation (CFD module, Comsol multiphysics) and dye testing. In preliminary experiments, oxygen sensors will be tested and a measurement method will be established, which allows to critically examine the oxygen diffusion at the growing, colonized vessel wall structures and to prevent cell necrosis. In parallel, oxygen transport and consumption will be simulated (CRE module, Comsol Multiphysics). In comparison to available porcine decellularized carotid scaffolds, the tubular 3D-printed vascular scaffolds will be endothelialized in the bioreactor with porcine endothelial cells (porcine endothelial aortic cells=PAEC), conditioned, biomechanically characterized and thus prepared for use in the large animal model pig. Furthermore, the colonization protocol will be optimized with regard to a sustained endothelial monolayer to counteract thrombosis and vascular occlusion after TEVG implantation in vivo.
DFG Programme
Research Grants
