Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell-based cartilage tissue engineering PMID: 32494742

ADC Targets in Oncology

2026-04-10

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

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.