Infectious bone defects pose significant clinical challenges due to persistent infection and impaired bone healing. Icam1⁺ macrophages were identified as crucial and previously unrecognized regulators in the repair of bone defects, where impaired oxidative phosphorylation within this macrophage subset represents a significant barrier to effective bone regeneration. To address this challenge, dual-responsive iron-doped barium titanate (BFTO) nanoparticles were synthesized with magnetic and ultrasonic properties. These nanoparticles were further loaded with the anti-inflammatory agent curcumin and coated with engineered mesenchymal stem cell membranes (EMM) modified with γ3 peptide, creating BFTO-Cur@EMM nanoparticles specifically designed to target Icam1⁺ macrophages. These nanoparticles were shown to disrupt bacterial biofilms under alternating magnetic fields (AMF) and to activate oxidative phosphorylation and osteogenic immune responses in Icam1+ macrophages via low-intensity pulsed ultrasound (LIPUS). Transcriptomic sequencing and validation experiments demonstrated that this approach activates oxidative phosphorylation (OXPHOS) by stimulating the JAK2-STAT3 pathway and inhibiting the MAPK-JNK pathway, thereby promoting the polarization of Icam1+ macrophages toward a pro-reparative phenotype and enhancing the secretion of pro-angiogenic and osteogenic cytokines. These nanoparticles were subsequently integrated into quaternized chitosan (QCS) and tricalcium phosphate (TCP) to create a bioink for three-dimensional (3D) printing anti-infection QT/BFTO-Cur@EMM bone repair scaffolds. In vivo studies indicated that these scaffolds significantly improved the healing of infectious bone defects without causing thermal damage to surrounding tissues. This work highlights the potential of this material and the targeting of Icam1⁺ macrophages as an effective strategy for simultaneously controlling infection and promoting bone regeneration.

中文翻译：

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工程磁压电纳米粒子增强支架破坏生物膜并激活 iCAM1+ 巨噬细胞中的氧化磷酸化，以实现感染性骨缺损再生


由于持续感染和骨愈合受损，感染性骨缺损带来了重大的临床挑战。Icam1⁺ 巨噬细胞被确定为骨缺损修复中的关键且以前未被识别的调节因子，其中该巨噬细胞亚群内氧化磷酸化受损代表了有效骨再生的重要障碍。为了应对这一挑战，合成了具有磁性和超声特性的双响应铁掺杂钛酸钡 （BFTO） 纳米颗粒。这些纳米颗粒进一步加载了抗炎剂姜黄素，并包被了用 γ3 肽修饰的工程间充质干细胞膜 （EMM），从而产生了专门设计用于靶向 Icam1 + 巨噬细胞的 BFTO ^Cur@EMM纳米颗粒。这些纳米颗粒被证明可以在交变磁场 （AMF） 下破坏细菌生物膜，并通过低强度脉冲超声 （LIPUS） 激活 Icam1+ 巨噬细胞中的氧化磷酸化和成骨免疫反应。转录组测序和验证实验表明，这种方法通过刺激 JAK2-STAT3 通路和抑制 MAPK-JNK 通路来激活氧化磷酸化 （OXPHOS），从而促进 Icam1+ 巨噬细胞向促修复表型极化，并增强促血管生成和成骨细胞因子的分泌。这些纳米颗粒随后被整合到季铵化壳聚糖 （QCS） 和磷酸三钙 （TCP） 中，以创建用于三维 （3D） 打印抗感染 QT/BFTO-Cur@EMM 骨修复支架的生物墨水。体内研究表明，这些支架显着改善了感染性骨缺损的愈合，而不会对周围组织造成热损伤。 这项工作强调了这种材料的潜力以及靶向 Icam1 ⁺ 巨噬细胞作为同时控制感染和促进骨再生的有效策略。