Molecular co-assembled strategy tuning protein conformation for cartilage regeneration

Chengkun Zhao, Xing Li, Xiaowen Han, Zhulian Li, Shaoquan Bian, Weinan Zeng, Mingming Ding, Jie Liang, Qing Jiang, Zongke Zhou, Yujiang Fan, Xingdong Zhang and Yong Sun ()
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Chengkun Zhao: Sichuan University
Xing Li: Sichuan University
Xiaowen Han: Mianyang Central Hospital
Zhulian Li: 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
Qing Jiang: Sichuan University
Zongke Zhou: West China Hospital, Sichuan University
Yujiang Fan: Sichuan University
Xingdong Zhang: Sichuan University
Yong Sun: Sichuan University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-45703-3

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