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

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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. Herein, we report 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 (GelMA) and assembled via 3D bioprinting into a stratified osteochondral construct. The model exhibited favorable cell viability, proliferation, and organized microtissue formation, validating its biological functionality. An OA-like microenvironment was induced with lipopolysaccharide (LPS), which significantly elevated pro-inflammatory cytokines. Treatment with diclofenac, dexamethasone, or curcumin markedly attenuated this response, reducing TNF-α, 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-supported 3D osteochondral platform reproduces key features of native joint tissue and holds promise for OA research, drug screening, and regenerative medicine.