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- Title
Molecular co-assembled strategy tuning protein conformation for cartilage regeneration.
- Authors
Zhao, Chengkun; Li, Xing; Han, Xiaowen; Li, Zhulian; Bian, Shaoquan; Zeng, Weinan; Ding, Mingming; Liang, Jie; Jiang, Qing; Zhou, Zongke; Fan, Yujiang; Zhang, Xingdong; Sun, Yong
- 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. The assembly of oligopeptide and polypeptide molecules can reconstruct various ordered advanced structures. Here the authors develop a "molecular velcro"-inspired amphiphilic supramolecular co-assembly strategy, which improves the mechanical strength and cartilaginous regeneration efficiency through conformation transition.
- Subjects
CARTILAGE regeneration; BONE regeneration; PROTEIN conformation; KNEE joint; MOLECULAR dynamics; OLIGOPEPTIDES; INTERMOLECULAR interactions
- Publication
Nature Communications, 2024, Vol 15, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-45703-3