炎性细胞因子清除和巨噬细胞代谢重编程,以协调炎性骨再生
Inflammatory cytokine scavenging and macrophage metabolism reprogramming to orchestrate inflammatory bone regeneration.
Inflammatory cytokine scavenging and macrophage metabolism reprogramming to orchestrate inflammatory bone regeneration.
炎性骨缺损在牙周炎和骨髓炎等感染性疾病中,由于持续性炎症和骨再生受损而构成重大挑战。当前的治疗策略往往无法同时解决免疫失调和成骨缺陷。在此,我们开发了一种炎性细胞因子清除方法,利用抗炎M2巨噬细胞膜中和骨愈合环境中的炎性细胞因子,并合成了硒掺杂生物活性玻璃纳米颗粒(Se-NPs)以重编程巨噬细胞代谢,从而为炎性骨再生创造有利环境。该纳米球通过将Se-NPs包裹于M2巨噬细胞膜内制备而成(M2@Se-NPs)。这些纳米球利用其抗炎能力及细胞因子受体清除TNF-α和IL-6,同时硒离子的持续释放通过NRF2/NF-κB通路重编程巨噬细胞代谢,恢复线粒体稳态并促进M2极化。M2@Se-NPs有效减轻了巨噬细胞炎症并抑制了NF-κB活化。经M2@Se-NPs处理的巨噬细胞条件培养基进一步增强了骨髓基质细胞的成骨分化,并促进了人脐静脉内皮细胞的血管生成。在小鼠炎性颅骨缺损模型中,M2@Se-NPs不仅通过下调TNF-α和上调ARG-1减轻局部炎症,还显著增强了成骨分化和骨基质形成。本研究证明了M2@Se-NPs在免疫调节、血管生成和骨修复中的三重治疗作用,为炎性骨再生提供了一种新型仿生解决方案。
Inflammatory bone defects pose significant challenges due to persistent inflammation and impaired bone regeneration in infectious disorders such as periodontitis and osteomyelitis. Current therapeutic strategies often fail to address immune dysregulation and defective osteogenesis simultaneously. Here, we developed an inflammatory cytokine-scavenging approach using anti-inflammatory M2 macrophage membranes to neutralize inflammatory cytokines in the bone healing environment, and synthesized selenium-doped bioactive glass nanoparticles (Se-NPs) to reprogram macrophage metabolism, thereby creating a favorable environment for inflammatory bone regeneration. The nanospheres were prepared by encapsulating Se-NPs within M2 macrophage membranes (M2@Se-NPs). These nanospheres harness their anti-inflammatory capacity cytokine receptors to scavenge TNF-α and IL-6, while the sustained release of selenium ions reprograms macrophage metabolism the NRF2/NF-κB pathway, restoring mitochondrial homeostasis and promoting M2 polarisation. , M2@Se-NPs effectively attenuated macrophage inflammation and inhibited NF-κB activation. Conditioned medium from M2@Se-NP-treated macrophages further enhanced the osteogenic differentiation of bone marrow stromal cells and promoted angiogenesis of human umbilical vein endothelial cells. In a murine inflammatory cranial defect model, M2@Se-NPs not only mitigated local inflammation by downregulating TNF-α and upregulating ARG-1, but also significantly enhanced osteogenic differentiation and bone matrix formation. This study demonstrates the triple therapeutic roles of M2@Se-NPs in immune modulation, angiogenesis, and bone repair, presenting a novel biomimetic solution for inflammatory bone regeneration.
Ze He, Yu-Qing Mu, Wen-Dong Gao, Yao Liu, Shi-Bo Liu, Hang-Hang Liu, et al. Inflammatory cytokine scavenging and macrophage metabolism reprogramming to orchestrate inflammatory bone regeneration.. Materials horizons. 2026; doi:10.1039/d6mh00561f.
Ze He, Yu-Qing Mu, Wen-Dong Gao, Yao Liu, Shi-Bo Liu, Hang-Hang Liu, et al (2026). Inflammatory cytokine scavenging and macrophage metabolism reprogramming to orchestrate inflammatory bone regeneration.. Materials horizons. https://doi.org/10.1039/d6mh00561f
Ze He, Yu-Qing Mu, Wen-Dong Gao, Yao Liu, Shi-Bo Liu, Hang-Hang Liu, et al. Inflammatory cytokine scavenging and macrophage metabolism reprogramming to orchestrate inflammatory bone regeneration.[J]. Materials horizons, 2026 doi:10.1039/d6mh00561f.
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