3D-bioprinted osteochondral model based on hierarchical polymeric microarchitectures for in vitro osteoarthritis drug screening

Abstract

Compared to conventional two-dimensional (2D) or scaffold-free three-dimensional (3D) drug screening models, biomimetic osteochondral constructs offer superior physiological relevance for studying osteoarthritis (OA) and accelerating therapeutic discovery. This study reports the development of a polymeric microarchitecture (PM)- based 3D osteochondral model for drug screening applications. Microfluidics-assisted fabrication enabled the generation of cartilage-like and osteogenic microtissues by encapsulating chondrocytes and endothelial/osteoblast cells within PMs. These multicellular aggregates were embedded in gelatin methacryloyl and assembled via 3D bioprinting into a stratified osteochondral construct. The model exhibited favorable cell viability, high proliferation, and organized microtissue formation, validating its biological functionality. An OA-like microenvironment was induced using lipopolysaccharide, significantly elevating pro-inflammatory cytokines. Treatment with diclofenac, dexamethasone, or curcumin markedly attenuated this response, reducing tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-6 to 42.1, 193.5, and 193.5 pg/mL, respectively, while elevating the anti-inflammatory cytokine IL-10 to 90.2 pg/mL. Overall, this PM-based 3D osteochondral platform reproduces key features of native joint tissue and holds promise for OA research, drug screening, and regenerative medicine.  

Keywords

3D osteochondral model / Curcumin / Drug screening / Microfluidics / Porous microspheres

Funding

This work was funded by the National Natural Science Foundation of China (grant numbers: 32271410), the Science and Technology Projects in Fujian Province (grant numbers: 2022FX1 and 2023Y4008), the Natural Science Foundation of Fujian Province (grant number: 2022J01297), the Fundamental Research Funds for the Central Universities (grant number: ZQN-1107), and the Program for Innovative Research Team in Science and Technology in Fujian Province, Scientific Research Funds of Huaqiao University (grant number: 24BS132).

Conflict of Interest

The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

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