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Modification of adipose mesenchymal stem cells-derived small extracellular vesicles with fibrin-targeting peptide CREKA for enhanced bone repair.

Authors
  • Wu, Qi1, 2
  • Fu, Xiaoling1, 3
  • Li, Xian2
  • Li, Jing2
  • Han, Weiju2
  • Wang, Yingjun2, 4
  • 1 School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, PR China. , (China)
  • 2 National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, PR China. , (China)
  • 3 Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou, 510006, PR China. , (China)
  • 4 Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, 510006, PR China. , (China)
Type
Published Article
Journal
Bioactive Materials
Publisher
KeAi Publishing
Publication Date
Feb 01, 2023
Volume
20
Pages
208–220
Identifiers
DOI: 10.1016/j.bioactmat.2022.05.031
PMID: 35702606
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The process of bone repair is highly regulated by a large number of bioactive factors. Thus, a "cocktail" of bioactive factors supplemented to the defect sites is desirable for bone repair. In this regard, small extracellular vesicles (sEVs) derived from mesenchymal stem cells hold great potential in tissue repair. Nevertheless, the poor homing and retention of sEVs greatly limited their possible clinical application. In the present work, DMPE-PEG-CREKA was inserted into the membrane of sEVs released from adipose-derived mesenchymal stem cells to obtain CREKA functionalized sEVs (CREKA-sEVs), which could target fibrin to accumulate and retain in bone defects. Our results showed that CREKA-sEVs, like sEVs, promoted the osteogenic differentiation of BMSCs, the angiogenic property of HUVECs, and modulated the polarization of macrophages in vitro. Furthermore, due to the improved fibrin-binding and retention capacity of CREKA-sEVs, they enhanced the bone repair substantially in the rat femoral defect model. This study provided a new strategy to improve the therapeutic efficiency of sEVs and showed that CREKA-sEVs had great application value in bone tissue repair. © 2022 The Authors.

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