3D bioprinted in vitro bone models

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In the proposed project, 3D bioprinted in vitro bone models will be generated. Using extrusion-based bioprinting we want to create complex 3D structures mimicking the natural osteon structure. Our ambition is to involve primary human cells instead of immortalised cell lines to finally establish a 3D co-culture model of osteoblasts, osteoclasts, osteocytes and endothelial cells. Crucial points in this projects are 1) the development of an ink supporting both osteocyte differentiation, attachment and spreading of osteoblasts as well as osteoclast differentiation, 2) the spatial arrangement of the different cell species and 3) the inclusion of endothelial cells to study effects of bone cells on vascularization and vice versa. Osteocytes, as regulators of bone remodeling have rarely been involved before in bioprinted structures, due to the limited availability of these cells and their postmitotic character. We want to apply bioprinted human primary osteoblasts and trigger their transition to osteocytes in the printed constructs, since preliminary work on this topic already showed promising results. Osteocyte containing constructs will be seeded with osteoblasts and osteoclasts or osteoclast progenitors to mimic natural bone structure with osteoblasts and osteoclasts at the surface and osteocytes deeply embedded into the bone matrix. We furthermore plan to include components of bone ECM like collagen I and hydroxyapatite into the inks to get a more bone-like model. Finally, core-shell bioprinting will be used to include endothelial cells. Two different approaches will be followed, with endothelial cells in a hydrogel core surrounded by the other cell types or seeded into osteocyte-containing hollow strands. The 3D printed model is intended to test the response of bone tissue to bioactive agents like growth factors, drugs, bioactive ions as well as biomaterials extracts. This would help to reduce animal experiments at least at the early stages of biomaterials and drug development. Furthermore, the model will help to further understand the complex interaction between osteocytes, osteoblasts, osteoclasts and endothelial cells.