1. Academic Validation
  2. Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell-based cartilage tissue engineering

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

  • Sci Adv. 2020 May 22;6(21):eaaz5913. doi: 10.1126/sciadv.aaz5913.
Junmin Lee 1 2 3 Oju Jeon 4 5 Ming Kong 6 7 8 Amr A Abdeen 9 Jung-Youn Shin 4 Ha Neul Lee 10 Yu Bin Lee 4 5 Wujin Sun 1 2 3 Praveen Bandaru 1 2 3 Daniel S Alt 4 5 KangJu Lee 1 2 3 Han-Jun Kim 1 2 3 Sang Jin Lee 4 5 Somali Chaterji 11 12 Su Ryon Shin 7 8 Eben Alsberg 4 5 13 14 15 16 17 18 Ali Khademhosseini 1 2 3 7 8 19 20 21
Affiliations

Affiliations

  • 1 Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 2 Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 3 California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 4 Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • 5 Department of Bioengineering, University of Illinois-Chicago, Chicago, IL 60607, USA.
  • 6 College of Marine Life Science, Ocean University of China, Yushan Road, Qingdao, Shandong Province 266003, China.
  • 7 Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
  • 8 Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 9 Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
  • 10 Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 11 Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA.
  • 12 Center for Resilient Infrastructures, Systems, and Processes (CRISP), Purdue University, West Lafayette, IN 47907, USA.
  • 13 Department of Orthopaedics, University of Illinois-Chicago, Chicago, IL 60612, USA.
  • 14 Department of Orthopaedic Surgery, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • 15 National Center for Regenerative Medicine, Division of General Medical Sciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • 16 School of Dentistry, Kyung Hee University, Seoul 130-701, South Korea.
  • 17 Department of Pharmacology, University of Illinois-Chicago, Chicago, IL 60612, USA.
  • 18 Department of Mechanical and Industrial Engineering, University of Illinois-Chicago, Chicago, IL 60607, USA.
  • 19 Department of Chemical and Biomolecular Engineering, Henry Samueli School of Engineering and Applied Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 20 Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 21 Terasaki Institute for Biomedical Innovation Los Angeles, CA 90064, 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.

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