한빛사 논문
Junmin Lee1,2,3,*, Oju Jeon4,5,*, Ming Kong6,7,8, Amr A. Abdeen9, Jung-Youn Shin4, Ha Neul Lee10, Yu Bin Lee4,5, Wujin Sun1,2,3, Praveen Bandaru1,2,3, Daniel S. Alt4,5, KangJu Lee1,2,3, Han-Jun Kim1,2,3, Sang Jin Lee4,5, Somali Chaterji11,12, Su Ryon Shin7,8, Eben Alsberg4,5,13,14,15,16,17,18,† and Ali Khademhosseini1,2,3,7,8,19,20,21,†
1Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
2Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA.
3California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA 90095, USA.
4Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
5Department of Bioengineering, University of Illinois-Chicago, Chicago, IL 60607, USA.
6College of Marine Life Science, Ocean University of China, Yushan Road, Qingdao, Shandong Province 266003, China.
7Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
8Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
9Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
10Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
11Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA.
12Center for Resilient Infrastructures, Systems, and Processes (CRISP), Purdue University, West Lafayette, IN 47907, USA.
13Department of Orthopaedics, University of Illinois-Chicago, Chicago, IL 60612, USA.
14Department of Orthopaedic Surgery, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
15National Center for Regenerative Medicine, Division of General Medical Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
16School of Dentistry, Kyung Hee University, Seoul 130-701, South Korea.
17Department of Pharmacology, University of Illinois-Chicago, Chicago, IL 60612, USA.
18Department of Mechanical and Industrial Engineering, University of Illinois-Chicago, Chicago, IL 60607, USA.
19Department of Chemical and Biomolecular Engineering, Henry Samueli School of Engineering and Applied Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
20Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
21Terasaki Institute for Biomedical Innovation Los Angeles, CA 90064, USA.
†Corresponding author.
*These authors contributed equally to this work.
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.
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