An electrostatic co-assembled extracellular vesicles infused hydrogel for bone regeneration in aged defects

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • Xiongjinfu Zhang - , Soochow University (Author)
  • Xingzhi Liu - , Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Author)
  • Yi Wang - , Soochow University (Author)
  • Can Zhu - , Soochow University (Author)
  • Daihui Liu - , Soochow University (Author)
  • Yi Zheng - , Soochow University (Author)
  • Yixin Zhang - , Center for Molecular Bioengineering (B CUBE), Chair of Biomolecular Interactions (Author)
  • Huilin Yang - , Soochow University (Author)
  • Yong Xu - , Soochow University (Author)
  • Qin Shi - , Soochow University (Author)

Abstract

Age-related bone defects remain challenging due to the reduced osteogenic capacity of aged bone marrow mesenchymal stem cells (A-BMSCs). An injectable hydrogel incorporating extracellular vesicles (EVs) from young BMSCs (Y-EVs) was designed to enhance bone regeneration. The hydrogel, composed of star-PEG-KA7 and polyphosphate-gelatin (P-GA, generated by conjugating imidazole-modified polyphosphate (PolyP-Im) with gelatin (GA), encapsulates Y-EVs to form the P-GA/KA7@Y-EVs system. In vitro, Y-EVs promoted osteogenic differentiation and alleviated senescence in A-BMSCs, while the hydrogel provided injectability, biocompatibility, and sustained release. In vivo, P-GA/KA7@Y-EVs significantly improved cranial bone regeneration in aged rats, surpassing Y-EVs or hydrogel alone. Transcriptomic and microRNA analyses indicated that Y-EVs rejuvenated A-BMSCs by modulating PI3K-Akt, TGF-β, and MAPK pathways, supported by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment. This EVs-infused bioactive hydrogel offers a minimally invasive and effective strategy for age-related bone regeneration.

Details

Original languageEnglish
Article number124254
JournalBiomaterials
Volume334
Publication statusPublished - Nov 2026
Peer-reviewedYes

External IDs

PubMed 42105728
ORCID /0000-0002-6669-4995/work/223386589

Keywords

Keywords

  • Age-related bone defects, Extracellular vesicles, Injectable hydrogel, Mesenchymal stem cells, Senescence