Abstract
Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effective therapeutic tool for repairing bone defects. Although metal-organic framework (MOF) scaffolds are promising strategies for bone tissue regeneration, their potential use for exosome loading remains unexplored. In this study, motivated by the potential advantages of hADSCs-Exos and Mg-GA MOF, we designed and synthesized an exosome-functionalized cell-free PLGA/Mg-GA MOF (PLGA/Exo-Mg-GA MOF) scaffold, taking using of the benefits of hADSCs-Exos, Mg2+, and gallic acid (GA) to construct unique nanostructural interfaces to enhance osteogenic, angiogenic and anti-inflammatory capabilities simultaneously. Our in vitro work demonstrated the beneficial effects of PLGA/Exo-Mg-GA MOF composite scaffolds on the osteogenic effects in human bone marrow-derived mesenchymal stem cells (hBMSCs) and angiogenic effects in human umbilical endothelial cells (HUVECs). Slowly released hADSCs-Exos from composite scaffolds were phagocytosed by co-cultured cells, stabilized the bone graft environment, ensured blood supply, promoted osteogenic differentiation, and accelerated bone reconstruction. Furthermore, our in vivo experiments with rat calvarial defect model showed that PLGA/Exo-Mg-GA MOF scaffolds promoted new bone formation and satisfactory osseointegration. Overall, we provide valuable new insights for designing exosome-coated nanocomposite scaffolds with enhanced osteogenesis property.
Graphical abstract. Scheme showing the fabrication and mechanism of exosome-functionalized PLGA/Mg-GA MOF scaffolds for accelerated bone regeneration. The PLGA/Mg-GA MOF composite scaffold was fabricated using a polymer blend of PLGA and Mg-GA MOF using electrospinning. Human ADSCs-derived exosomes were then incorporated onto the PLGA/Mg-GA MOF composite scaffold and the functionalized scaffold implanted into a rat calvarial defect to evaluate bone regeneration, blood vessel formation, and anti-inflammation properties. [Display omitted]
•PLGA/Exo-Mg-GA MOF scaffolds with nanostructures were synthesized, on which exosomes were densely deposited on the above scaffolds.•Composite scaffolds with exosomes can actualize the slow release of exosomes, Mg ions and gallic acid.•PLGA/Exo-Mg-GA MOF scaffolds exhibit great biocompatibility and osteogenic differentiation of hBMSCs.•PLGA/Exo-Mg-GA MOF scaffolds have excellent osteogenic, pro-angiogenic and anti-inflammatory activity.