ArchiTissue - 3D-Architecture of biohybrid cardiovascular implants by additive manufacturing

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The production of biohybrid implants requires the combination of living cells and non-living scaffolds in a specific 3D arrangement to obtain tissues that recapitulate native ones in their composition and function. Ideally the scaffold provides the overall geometry and structural stability and at the same time defines the 3D microenvironment with tailored properties to guide cellular growth and extracellular matrix synthesis. The scaffold design and the material properties affect the cell behavior in multiple ways, ultimately influencing the final tissue’s function. The aim of this project is to investigate the influence of precisely defined 3D scaffold architectures on the maturation of functional biohybrid implants. The project relies on the capability of additive manufacturing techniques to control the spatial distribution of pore size, shape and interconnectivity as well as mechanical and structural properties of polymeric scaffolds. In ArchiTissue, we will apply initiator-free laser polymerization of cytocompatible pre-polymers in combination with stereolithography (SL) to create a variety of microstructures as building blocks which can be selectively assembled into 3D macro geometries. The effect of the so obtained microarchitectures on cell behavior will be investigated with mono- and co-culture of smooth muscle cells and endothelial cells, in structures of increasing complexity. Indeed, the high degree of freedom associated with the fabrication technique allows to create scaffolds exhibiting non homogeneous composition and anisotropic properties typical of native tissues. Based on the results, the framework conditions for the development of a multi-layer, biohybrid heart valve will be determined. These conditions and parameters will be collected in a structural catalogue which will serve as a general platform for biohybrid implants as well as input for a maturation model of such implants. The three layers of a heart valve leaflet, the collagen-rich fibrosa, the glycosaminoglycan-rich spongiosa and the elastin-rich ventricularis, will be realized by the cell colonization of the scaffold in ad-hoc developed bioreactors. For this purpose, the mechanical properties and the microarchitecture are first tailored for each layer to influence the behavior of the endothelial and smooth muscle cells, especially with respect to the production of the extracellular matrix.The following scientific questions will be addressed to achieve the project’s aim:1) Creation of 3D architectures by combination of micro- and macroscale structuring by combining multiphoton polymerization and SL2) Investigation of the interaction between 3D architecture and cells under static and dynamic cultivation in bioreactors3) Development of a multi-layered biomimetic biohybrid model for heart valve tissue engineering