Biomimetic Fibers Based on Equidistant Micropillar Arrays Determines Chondrocyte Fate Via Mechanoadaptability.

It is recognized that the changes in the physical properties of extracellular matrix result in fine-tuned cell responses including cell morphology, proliferation and differentiation. In this study, a novel patterned equidistant micropillar substrate based on polydimethylsiloxane (PDMS) was designed to mimic the collagen fiber-like network of the cartilage matrix. By changing the component of the curing agent to an oligomeric base, we obtained micropillar substrates with the same topology but different stiffnesses and found that chondrocytes seeded onto the soft micropillar substrate maintain their phenotype by gathering type II collagen and aggrecan more effectively than those seeded onto the stiff micropillar substrate. Moreover, chondrocytes sensed and responded to micropillar substrates with different stiffnesses by altering the ECM-cytoskeleton-focal adhesion axis. We then found that the soft substrate-preserved chondrocyte phenotype was dependent on the activation of Wnt/β-catenin signaling at a high expression level. Finally, we indicated the changes in osteoid-like region formation and cartilage phenotype loss in the stiffened sclerotic area of osteoarthritis mouse cartilage to validate the cell behavior changes triggered by micropillar substrates with different stiffnesses. This study provided the change in cell behaviors that are more similar to those of real chondrocytes at tissue level during the transition from a normal state to a state of osteoarthritis. This article is protected by copyright. All rights reserved.