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architectures. These attributes collectively enable GelMA to mimic the native cellular
microenvironment in vitro, thereby reducing the need for repetitive preliminary experiments and
providing a standardized platform for applications such as tissue engineering and organ-on-a-chip
systems. Lipopolysaccharide (LPS) is the most abundant component within the cell wall of Gram-
negative bacteria. It can stimulate the release of inflammatory cytokines in various cell types,
leading to an acute inflammatory response towards pathogens. OA is a low-grade inflammatory
condition, and the elevation of the levels of LPS in obesity and metabolic syndrome could
contribute to OA 38,39 .
Motivated by these considerations, we demonstrate the fabrication of an in vitro OA model
composed of hierarchical osteochondral tissue architectures using a combinatorial approach of
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microfluidic technique and 3D bioprinting . Initially, PMs were first prepared using the
microfluidic technique. Further, mouse embryonic chondrocytes (C518) were then harbored into
the PMs to construct cartilaginous cellular microtissues (C-MTs). In addition, mouse embryonic
osteoblasts (MC3T3-E1) and mouse aorta endothelial cells (MAEC) were simultaneously
encapsulated in a separate batch of PMs to construct endothelium osteoblastic microtissues (EO-
MTs). Then, the C-MTs and EO-MTs were mixed with GelMA as a bioink for building a
hierarchical osteochondral architecture using the 3D bioprinting approach (Figure 1). Further, the
OA condition was induced to the designed hierarchical architectures by exposing the osteochondral
model to LPS. Moreover, curcumin (Cur) is a natural anti-inflammatory agent used for treating
medical conditions for many years. Several reports indicated its potency to target multiple
inflammatory diseases, including OA, rheumatoid arthritis, and other inflammatory arthritic
conditions 41-43 . Similarly, the synthetic glucocorticoid dexamethasone (Dex) has been widely
employed in intra-articular therapy for OA due to its potent anti-inflammatory effects, effectively
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