静电共组装细胞外囊泡复合水凝胶用于老年骨缺损修复的研究
An Electrostatic Co-Assembled Extracellular Vesicles Infused Hydrogel for Bone Regeneration in Aged Defects
Xiongjinfu Zhang, Xingzhi Liu, Yi Wang, Can Zhu, Daihui Liu, Yi Zheng, Yixin Zhang, Huilin Yang, Yong Xu, Qin Shi
Journal：BIOMATERIALS
IF：13.6
DOI：10.1016/j.biomaterials.2026.124254
PMID：42105728
Published：2026-04-28
research field：生物医学工程衰老研究再生医学骨组织工程纳米医学
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.
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