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Updated: Dec 19, 2025
3D Hydrogel Scaffolds for Articular Chondrocyte Culture and Cartilage Generation
Published on: October 7, 2015
Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell-based cartilage
Junmin Lee1,2,3, Oju Jeon4,5, Ming Kong6,7,8
1Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Abstract:
Despite great progress in biomaterial design strategies for replacing damaged articular cartilage, prevention of stem cell-derived chondrocyte hypertrophy and resulting inferior tissue formation is still a critical challenge. Here, by using engineered biomaterials and a high-throughput system for screening of combinatorial cues in cartilage microenvironments, we demonstrate that biomaterial cross-linking density that regulates matrix degradation and stiffness-together with defined presentation of growth factors, mechanical stimulation, and arginine-glycine-aspartic acid (RGD) peptides-can guide human mesenchymal stem cell (hMSC) differentiation into articular or hypertrophic cartilage phenotypes. Faster-degrading, soft matrices promoted articular cartilage tissue formation of hMSCs by inducing their proliferation and maturation, while slower-degrading, stiff matrices promoted cells to differentiate into hypertrophic chondrocytes through Yes-associated protein (YAP)-dependent mechanotransduction. in vitro and in vivo chondrogenesis studies also suggest that down-regulation of the Wingless and INT-1 (WNT) signaling pathway is required for better quality articular cartilage-like tissue production.
