Molecular co-assembled strategy tuning protein conformation for cartilage regeneration

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-024-45703-3
Popis: 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.
Databáze: Directory of Open Access Journals