Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell-based cartilage tissue engineering

• Published in: Science advances Vol. 6; no. 21; p. eaaz5913
• Main Authors: Lee, Junmin, Jeon, Oju, Kong, Ming, Abdeen, Amr A, Shin, Jung-Youn, Lee, Ha Neul, Lee, Yu Bin, Sun, Wujin, Bandaru, Praveen, Alt, Daniel S, Lee, KangJu, Kim, Han-Jun, Lee, Sang Jin, Chaterji, Somali, Shin, Su Ryon, Alsberg, Eben, Khademhosseini, Ali
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.05.2020
• Subjects: Biocompatible Materials - metabolism; Cartilage, Articular - metabolism; Cell Differentiation; Health and Medicine; Materials Science; Mechanotransduction, Cellular - physiology; Mesenchymal Stem Cells - metabolism; Phenotype; SciAdv r-articles; Stem Cells; Tissue Engineering - methods
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.aaz5913

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.