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Molecular co-assembled strategy tuning protein conformation for cartilage regeneration

Author

Listed:
  • Chengkun Zhao

    (Sichuan University
    Sichuan University)

  • Xing Li

    (Sichuan University
    Sichuan University)

  • Xiaowen Han

    (Mianyang Central Hospital)

  • Zhulian Li

    (Sichuan University
    Sichuan University)

  • Shaoquan Bian

    (Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences)

  • Weinan Zeng

    (West China Hospital, Sichuan University)

  • Mingming Ding

    (Sichuan University)

  • Jie Liang

    (Sichuan University
    Sichuan University
    Sichuan University)

  • Qing Jiang

    (Sichuan University
    Sichuan University)

  • Zongke Zhou

    (West China Hospital, Sichuan University)

  • Yujiang Fan

    (Sichuan University
    Sichuan University)

  • Xingdong Zhang

    (Sichuan University
    Sichuan University)

  • Yong Sun

    (Sichuan University
    Sichuan University)

Abstract

The assembly of oligopeptide and polypeptide molecules can reconstruct various ordered advanced structures through intermolecular interactions to achieve protein-like biofunction. Here, we develop a “molecular velcro”-inspired peptide and gelatin co-assembly strategy, in which amphiphilic supramolecular tripeptides are attached to the molecular chain of gelatin methacryloyl via intra-/intermolecular interactions. We perform molecular docking and dynamics simulations to demonstrate the feasibility of this strategy and reveal the advanced structural transition of the co-assembled hydrogel, which brings more ordered β-sheet content and 10-fold or more compressive strength improvement. We conduct transcriptome analysis to reveal the role of co-assembled hydrogel in promoting cell proliferation and chondrogenic differentiation. Subcutaneous implantation evaluation confirms considerably reduced inflammatory responses and immunogenicity in comparison with type I collagen. We demonstrate that bone mesenchymal stem cells-laden co-assembled hydrogel can be stably fixed in rabbit knee joint defects by photocuring, which significantly facilitates hyaline cartilage regeneration after three months. This co-assembly strategy provides an approach for developing cartilage regenerative biomaterials.

Suggested Citation

  • Chengkun Zhao & Xing Li & Xiaowen Han & Zhulian Li & Shaoquan Bian & Weinan Zeng & Mingming Ding & Jie Liang & Qing Jiang & Zongke Zhou & Yujiang Fan & Xingdong Zhang & Yong Sun, 2024. "Molecular co-assembled strategy tuning protein conformation for cartilage regeneration," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45703-3
    DOI: 10.1038/s41467-024-45703-3
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    References listed on IDEAS

    as
    1. Yeqiang Zhou & Fan Fan & Jinling Zhao & Zhaoding Wang & Rui Wang & Yi Zheng & Hang Liu & Chuan Peng & Jianshu Li & Hong Tan & Qiang Fu & Mingming Ding, 2022. "Intrinsically fluorescent polyureas toward conformation-assisted metamorphosis, discoloration and intracellular drug delivery," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Tuo Deng & Dongxiu Gao & Xuemei Song & Zhipeng Zhou & Lixiao Zhou & Maixian Tao & Zexiu Jiang & Lian Yang & Lan Luo & Ankun Zhou & Lin Hu & Hongbo Qin & Mingyi Wu, 2023. "A natural biological adhesive from snail mucus for wound repair," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Sarah McLaughlin & Brian McNeill & James Podrebarac & Katsuhiro Hosoyama & Veronika Sedlakova & Gregory Cron & David Smyth & Richard Seymour & Keshav Goel & Wenbin Liang & Katey J. Rayner & Marc Ruel , 2019. "Injectable human recombinant collagen matrices limit adverse remodeling and improve cardiac function after myocardial infarction," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
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    5. Hai Lei & Liang Dong & Ying Li & Junsheng Zhang & Huiyan Chen & Junhua Wu & Yu Zhang & Qiyang Fan & Bin Xue & Meng Qin & Bin Chen & Yi Cao & Wei Wang, 2020. "Stretchable hydrogels with low hysteresis and anti-fatigue fracture based on polyprotein cross-linkers," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
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