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Regulatory effects of ApoNVs on macrophages, HUVECs and HAVSMCs. a) Schematic illustration of the experimental design used to assess the effect of ApoNVs on macrophages, HUVECs and HAVSMCs. b) Representative fluorescence images showing the cellular uptake of DiD‐labeled ApoNVs (red) by macrophages. The cytoskeleton F‐actin was stained with YF 488‐Phalloidin (green) and the nuclei were stained with DAPI (blue). c) Flow cytometry analysis of the expression of the inflammatory M1 marker CD86 and the anti‐inflammatory M2 marker CD206 in macrophages treated with or without ApoNVs. d,e) NO (d) and TNF‐α (e) production by macrophages with or without ApoNVs treatment. f) Representative fluorescence images showing the cellular uptake of DiD‐labeled ApoNVs (red) by HUVECs. The cytoskeleton F‐actin was stained with YF 488‐Phalloidin (green), and the nuclei were stained with DAPI (blue). g) HUVEC proliferation with or without ApoNV treatment. h,i) Tube formation of HUVECs with or without ApoNV treatment. j,k) Chemotactic migration of HUVECs with or without ApoNV treatment. l) Representative fluorescence images showing the cellular uptake of DiD‐labeled ApoNVs (red) by HAVSMCs. The cytoskeleton F‐actin was stained with YF 488‐Phalloidin (green) and the nuclei were stained with DAPI (blue). m) HAVSMC proliferation with or without ApoNV treatment. n,o) Chemotactic migration of HAVSMCs with or without ApoNV treatment. Data are presented as the mean ± standard error of the mean (SEM) (n = 3 per group). Statistical significance was determined by one‐way ANOVA with Tukey's test (d, e) and an independent unpaired two‐tailed Student's t test (g, i, k, m, o). *p < 0.05, **p < 0.01, ***p < 0.001 and ns: not significant.
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Modulating inflammation is crucial for repairing vascular injury. Phagocytosis of apoptotic cells represents an effective mechanism for attenuating inflammation and improving regeneration during natural healing. However, strategies for repairing vascular injuries using biomaterials derived from apoptotic cells are still undeveloped. Herein, apoptot...
Citations
... A cellpenetrating peptide has been utilized to modify apoEVs for the treatment of ischemic stroke, yielding promising results [20]. A research team successfully conjugated P-selectin binding peptide to apoEVs and confirmed that the targeting ability of apoEVs to injured arteries significantly increased [21]. Taking these inspirations, we propose that the strategic integration of PMSC-apo-EVs' inherent bone regulatory ability with engineering Graphical Abstract technologies could potentially instigate a paradigm shift in the therapeutic conundrum of HO. ...
Heterotopic Ossification (HO), refers to pathological extra skeletal bone formation, and there are currently no reliable methods except surgery to reverse these unexpected calcified tissues. Apoptotic vesicles (ApoEVs) are membrane-bound vesicles released by apoptotic cells, which are involved in metabolism regulation and intercellular communication. Due to its superior trauma-healing ability, the hard palate mucosa is expected to become an essential resource for tissue engineering. This work presents a minimally invasive nanotherapy based on an engineered apoEV. Briefly, apoEVs were extracted from hard palate mucosa and engineered with bone-targeting peptide SDSSD to treat HO. This engineered apoEV not only can achieve directed localization of heterotopic bones but also has the compelling dual function of promoting osteoclastic differentiation while inhibiting osteogenic differentiation. The underlying mechanism involves the activation of Hippo and Notch pathways, as well as the regulation of pyrimidine metabolism. We envision that this engineered apoEV may be a feasible and effective strategy for reversing HO.
Graphical Abstract