Bioprinted tissue models for substance evaluation

The bioprinting technology allows the creation of three-dimensional (3D) tissues in an additive manufacturing process with spatial control of cells, bioactive materials and molecules and therefore reflects the inherent complexity of native tissues to a high degree. As applied university we focus on industry-driven projects. We are developing bioprinting solutions in the fields of the cosmetic and pharma industry. The current bioprinting solution offers the following specifications: i) inkjet- and extruder-based printheads with temperature control for cell jetting and contact printing into well plates, ii) different cell-compatible printable matrices (bioinks), iii) a photopolymerization unit to crosslink bioinks at 365 nm and iv) a cell mixer to avoid cell sedimentation in the print cartridge while printing. For tissue generation alternating layers of bioink and cells are printed to produce a multi-layered 3D tissue construct. In our aging population there is a huge demand for treatments of muscle-tendon related diseases. In an industry research project we are developing an all-in-one solution to produce and analyse printed in vitro muscle-tendon tissues in a customized well plate. Two posts in each well of the well plate will serve as anchor points to build muscle/tendon tissues. First, monocultures of primary human myoblasts and primary rat tenocytes were printed separately in a dumbbell-shape around the posts. After cell differentiation the myoblasts were stained positive for myosin heavy chain (MHC) and myotubes developed and for tendon the characteristic collagen I-distribution around the cell nuclei was detected. The printed muscle tissue is contracting on electrical stimulation and shows physiological functionality. The integration of electrodes in the well plates will allow electrical stimulation and subsequent read-out in the well plate. Nephrotoxicity is a major cause for effective drugs not being marketed. In a precompetitive research project we are reproducing parts of the nephron the so called proximal tubulus. In preliminary experiments we printed the proximal tubule of the kidney seeded with proximal tubule epithelial cells to cultivate them under physiological flow conditions. The development of standardized 3D in vitro tissue models combined with read-outs is a prerequisite for the future success of 3D tissues in substance testing and medicine in general. Disclosure: Funding: CTI, Project Numbers: 14331.1, 16313.1, SNF No.: 20PC21_161566 /