The integrated regeneration of cartilage and subchondral bone tissue remains a clinical challenge due to the complexity of osteochondral tissues. 3D bioprinting is an advanced biomanufacturing technology, which can easily realize the precise distribution of multiple biomaterials, cells and bioactive factors. It has great potential to reconstruct complex tissues and organs by applying 3D bioprinting technology. Thus, it is of great importance to develop a 3D multicellular scaffold that can simultaneously simulate the structure and functional characteristics of the osteochondral tissues.

By designing the bioinks incorporating inorganic biomaterials and the spatial distribution of mutiple cells, a research team from the Shanghai Institute of Ceramics of the Chinese Academy of Sciences (CAS) led by Prof. WU Chengtie and Prof. CHANG Jiang has constructed a multicellular system containing chondrocytes and mesenchymal stem cells by applying 3D bioprinting technology.

According to the researchers, the multicellular system simulated the anisotropic physiological characteristics of the osteochondral tissues and could efficiently promote the regeneration of osteochondral tissues. Result has been published in Materials Today.

The researchers developed a bioink based on Li-Mg-Si (LMS) bioceramics and applied the bioink to prepare a multicellular scaffold with 3D bioprinting. By controlling the composition and distribution of the bioinks and cells, a multicellular system containing chondrocytes and mesenchymal stem cells was constructed to simulate the anisotropic physiological environment of osteochondral tissues.

The bioprinted co-culture scaffold was designed with two layers, in which the top cartilage layer was hydrogel bioink loaded with chondrocytes, and the bottom subchondral bone layer was LMS bioceramics-containing bioinks loaded with mesenchymal stem cells. Such a constituent and spatial design of cells and bioinks well met the requirements of cell proliferation and differentiation in cartilage and subchondral bone.

Moreover, the LMS bioceramics-containing bioinks could not only simulate the component of bone, but also release bioactive ions to induce multiple cells towards specific differentiation, thus stimulated the regeneration of both cartilage and subchondral bone simultaneously.

The 3D bioprinted multicellular scaffolds exhibited excellent cell activities, capabilities of simultaneously modulating the specific differentiation of multiple cells in vitro and effectively accelerating the repair of large osteochondral defects in vivo. 

"With just one inorganic biomaterial, the bioink provids a favorable microenvironment for the proliferation and differentiation of multiple cells. With 3D bioprinting, a multicellular scaffold could be constructed to mimic the complex osteochondral tissues, and different types of cells could be accurately arranged in 3D space." Said Prof. WU.

The strategy provides new ideas for the reconstruction of complex tissues and organs in the human body.

The study was financially supported by the National Key Research and Development Project, the Natural Science Foundation of China and the Innovation Cross Team of CAS.

Combining LMS bioceramics-containing bioinks and multi-cells, a bilayered multicellular scaffold mimicking osteochondral tissues was successfully prepared by 3D bioprinting method. (Image by SICCAS)

3D bioprinted multicellular scaffolds exhibited excellent cell proliferation and spatial cell distribution mimicking osteochondral interface. (Image by SICCAS)

The effect of 3D bioprinted multicellular scaffolds on the repair of rabbit osteochondral defects. Histological analysis showed that the 3D bioprinted scaffolds can promote the regeneration of both cartilage and subchondral bone. (Image by SICCAS)