Projects

In the previous project 3D-Bioprinting important basics for the bioprinting of vascularized bone tissue could be achieved. Two hydrogels were identified which are able to support the relevant cell types in a suitable way. Furthermore, a 3D-Bioprinter was developed that integrates different printing technologies. With this, stable cubes of 1 cm edge length were printed. It could be shown in vitro as well as in vivo in a subcutaneous implantation model that printed endothelial cells are able to form blood vessels and printed mesenchymal stem cells can form a bone-specific calcified extracellular matrix. Thereby, the stiffness of the 3D-bioprinted constructs is approximately equivalent to that of native human soft tissue (approx. 1 kPa), that of native bone tissue is approx. 100,000 times higher (approx. 1 x 105 kPa). Therefore, one of the main goals of this follow-up project is the development of a combined printing process for printing cell-containing hydrogels and stability generating thermoplastics and/or calcium phosphate cements (CPC) in order to print vascularized bone replacement tissue with a stiffness equivalent to that of native bone tissue. The second main goal is the implementation of the so-called 4D-printing ("time" as fourth dimension), where the temporal and spatial maturation of the constructs shall be controlled by the additional spatially resolved printing of growth factors, differentiation factors and/or additional cell entities. The third main goal of this project is the in vivo validation of the printed 4D combination constructs in a physiologically relevant orthotopic bone healing model of the rat with respect to vascularization and bone formation. In particular, it will be investigated whether the quantity and/or quality of bone and blood vessel formation can be controlled by modulating the E-moduli of the printed constructs.