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these shortcomings for the efficient initial screening of therapeutic agents towards OA therapy 14,15 .
Typically, the two-dimensional (2D) cell culture of chondrocytes is considered a “model cell” for
OA in vitro. Comparatively, the three-dimensional (3D) models based on chondrocytes are more
reliable over the conventional 2D monolayers to investigate OA due to their simulations of cell-
cell and cell-extracellular matrix (ECM) interactions. Further advancements included developing
the scaffold-based 3D models as the screening platforms, which are capable of providing controlled
matrix elasticity for the co-culturing of multiple cell types (including bone cells) and investigations
of cell fate. Moreover, the encapsulated chondrocytes in 3D scaffolds could better maintain their
physiological phenotype and thus maintain the regeneration ability of the articular cartilage
compared to the 2D culture models 16,17 . Among the joint tissues, the subchondral bone cells play a
significant role in maintaining the proper cartilage matrix and the articular physiology by
interacting with each other 18,19 . In a case, Maihemuti and coworkers has proposed a 3D printed
porous multilayer scaffold based on cold-water fish skin gelatin for osteoarticular cartilage
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regeneration of damaged cartilage after arthritis . It was demonstrated that the simulation of the
physiological microstructure of articular cartilage and subchondral bone was essential to construct
a 3D scaffold-based OA model. In another case, Korpayev and colleagues designed a multilayered
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scaffold embedding chondrocytes and preosteoblastic cells as a biomimetic osteochondral model .
The close simulation and construction of bone joint structure and composition would benefit the
investigation of OA pathology and drug screening 22-24 .
Polymeric microarchitectures (PMs)-based scaffolds have attracted enormous attention from
researchers owing to their biocompatibility, excellent cell carrying capacity, and facilitate the ECM-
like environment for cell growth 25-27 . These PMs with exceptional porosity and interconnecting
windows substantially encapsulate the cells and enable their infiltration to the interiors, ensuring
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