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An electrostatic co-assembled extracellular vesicles infused hydrogel for bone regeneration in aged defects
Xiongjinfu Zhang1, Xingzhi Liu2, Yi Wang1
1Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute and Medical College of Soochow University, 899 Pinghai Road, Jiangsu, Suzhou, 215031, China.
None:
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.
