한빛사 논문
Junmin Lee 1,2,3,4,17, Oju Jeon 5,17, Jaekyung Koh 6, Han-Jun Kim 2, Sang Jin Lee 5,7, Yangzhi Zhu 2, Jihyeon Song 1, Yeji Lee 1, Rohollah Nasiri 2, KangJu Lee 2,8, Praveen Bandaru 2, Hyun-Jong Cho 9, Shiming Zhang 2,10, Natan R. Barros 2, Samad Ahadian 2, Heemin Kang 11,12, Mehmet R. Dokmeci 2, Joanna Lee 13, Dino Di Carlo 6, Eben Alsberg 5,14,15,16, Ali Khademhosseini 2,18
1Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Korea
2Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90064, USA
3School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeongbuk 37673, South Korea
4Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Incheon 21983, Republic of Korea
5Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL 60607, USA
6Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California-Los Angeles, Los Angeles, CA 90095, USA
7Biofunctional Materials, Division of Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Sai Ying Pun, Hong Kong SAR, PRC
8School of Healthcare Medical Engineering, Chonnam National University, Yeosu 59626, Republic of Korea
9College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea
10Department of Electrical and Electronic Engineering, The University of Hong Kong, Pok Fu Lam Rd, Lung Fu Shan, Hong Kong
11Department of Materials Science and Engineering, Korea University, Seoul 02841, Republic of Korea
12Department of Biomicrosystem Technology, Korea University, Seoul 02841, Republic of Korea
13Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA
14Department of Orthopaedic Surgery, University of Illinois at Chicago, Chicago, IL 60607, USA
15Department of Pharmacology and Regenerative Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
16Department of Mechanical and Industrial Engineering, University of Illinois at Chicago, Chicago, IL 60607, USA
17These authors contributed equally.
18Lead contact
Corresponding authors: Junmin Lee, Eben Alsberg, Ali Khademhosseini
Abstract
Within the complex microarchitecture of native cartilage tissue, the micromechanical properties of pericellular and extracellular matrices (PCM and ECM) potentially play important roles in developmental, physiological, and pathological processes. Here, we report a unique biomaterial-based engineering strategy to create cartilage-tissue equivalents possessing PCM-ECM microarchitecture of native cartilage, where human mesenchymal stem cell (hMSC)-laden soft microgels representing PCM are encapsulated in stiff hydrogels representing ECM. Mechanical property mismatches between soft PCM and stiff ECM under cyclic compression regulates hMSC proliferation and chondrogenesis. High PCM-ECM mechanical mismatch (softer PCM) and the presence of PCM degradation under cyclic compression individually or synergistically direct hMSC articular chondrogenesis through the proliferation-associated protein kinase C signaling pathway, whereas low PCM-ECM mechanical mismatch (stiffer PCM) is solely responsible for hMSC hypertrophic chondrogenesis through the yes-associated protein signaling pathway. Our findings highlight PCM-ECM mechanical property mismatch as a critical design cue under dynamic compression for hMSC-based cartilage repair.
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