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Spatially controlled multicellular differentiation of stem cells using triple factor-releasing metal–organic framework-coated nanoline arrays

Author

Listed:
  • Yeon-Woo Cho

    (Sungkyunkwan University (SKKU)
    Chung-Ang University)

  • Min-Ji Kang

    (Sungkyunkwan University (SKKU))

  • Joon-Ha Park

    (Sungkyunkwan University (SKKU))

  • Yun-Sik Eom

    (Sungkyunkwan University (SKKU)
    Chung-Ang University)

  • Tae-Hyung Kim

    (Sungkyunkwan University (SKKU)
    SKKU)

Abstract

Improved in vitro models are needed for regenerative therapy and drug screening. Here, we report on functionally aligned nanoparticle-trapped nanopattern arrays for spatially controlled, precise mesenchymal stem cell differentiation on a single substrate. The arrays comprise nanohole and nanoline arrays fabricated through interference lithography and selectively capture of UiO-67 metal–organic frameworks on nanoline arrays with a 99.8% efficiency using an optimised asymmetric spin-coating method. The UiO-67 metal–organic frameworks contain three osteogenic differentiation factors for sustained release over four weeks. The combination of differentiation factors and patterned array allows for generation of adipocytes, osteoblasts, and adipocyte–osteoblast mixtures on nanohole arrays, nanoline arrays, and at the nanohole–nanoline interface, respectively, with mature osteoblasts exhibiting higher marker expression and mineralisation. The sustained release patterned array holds potential for constructing advanced therapeutic and disease state in vitro cellular models.

Suggested Citation

  • Yeon-Woo Cho & Min-Ji Kang & Joon-Ha Park & Yun-Sik Eom & Tae-Hyung Kim, 2025. "Spatially controlled multicellular differentiation of stem cells using triple factor-releasing metal–organic framework-coated nanoline arrays," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56373-0
    DOI: 10.1038/s41467-025-56373-0
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    1. Ryuhei Hayashi & Toru Okubo & Yuji Kudo & Yuki Ishikawa & Tsutomu Imaizumi & Kenji Suzuki & Shun Shibata & Tomohiko Katayama & Sung-Joon Park & Robert D. Young & Andrew J. Quantock & Kohji Nishida, 2022. "Generation of 3D lacrimal gland organoids from human pluripotent stem cells," Nature, Nature, vol. 605(7908), pages 126-131, May.
    2. Jong-Chan Park & So-Yeong Jang & Dongjoon Lee & Jeongha Lee & Uiryong Kang & Hongjun Chang & Haeng Jun Kim & Sun-Ho Han & Jinsoo Seo & Murim Choi & Dong Young Lee & Min Soo Byun & Dahyun Yi & Kwang-Hy, 2021. "A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Ryuhei Hayashi & Yuki Ishikawa & Yuzuru Sasamoto & Ryosuke Katori & Naoki Nomura & Tatsuya Ichikawa & Saori Araki & Takeshi Soma & Satoshi Kawasaki & Kiyotoshi Sekiguchi & Andrew J. Quantock & Motokaz, 2016. "Co-ordinated ocular development from human iPS cells and recovery of corneal function," Nature, Nature, vol. 531(7594), pages 376-380, March.
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