Micromechanical property mismatch between pericellular and extracellular matrices regulates stem cell articular and hypertrophic chondrogenesis

Junmin Lee, Oju Jeon, Jaekyung Koh, Han Jun Kim, Sang Jin Lee, Yangzhi Zhu, Jihyeon Song, Yeji Lee, Rohollah Nasiri, Kang Ju Lee, Praveen Bandaru, Hyun Jong Cho, Shiming Zhang, Natan R. Barros, Samad Ahadian, Heemin Kang, Mehmet R. Dokmeci, Joanna Lee, Dino Di Carlo, Eben AlsbergAli Khademhosseini

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)475-492
Number of pages18
Issue number2
Publication statusPublished - 2023 Feb 1

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Inc.


  • MAP 6: Development.
  • articular chondrogenesis
  • cartilage tissue engineering
  • dynamic compression
  • extracellular matrix
  • human mesenchymal stem cells
  • hypertrophic chondrogenesis
  • micromechanical property mismatch
  • pericellular matrix
  • proliferation-associated protein kinase C signaling
  • yes-associated protein signaling

ASJC Scopus subject areas

  • General Materials Science


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