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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.

Keywords: Microfluidics; Porous microspheres; Drug screening; 3D osteochondral model;

Curcumin

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