硼硅酸盐生物活性玻璃(BSG)和FeO磁性纳米颗粒支架对种植体相关骨感染的初步治疗证据。
Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and FeO magnetic nanoparticle scaffold on implant-associated bone infection.
作者信息
Jin Ying, Liu Hang, Chu Lei, Yang Jin, Li Xiuyang, Zhou Hang, Jiang Haitao, Shi Lei, Weeks Jason, Rainbolt Joshua, Yang Changjiang, Xue Thomas, Pan Haobo, Deng Zhongliang, Xie Chao, Cui Xu, Ren Youliang
机构信息
Department of Orthopaedics, Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong Distinct, Chongqing, 400010, PR China.
Department of Orthopaedics, Zunyi Medical University, Zunyi, Guizhou, PR China.
出版信息
Bioact Mater. 2024 Jun 8;40:148-167. doi: 10.1016/j.bioactmat.2024.05.040. eCollection 2024 Oct.
Implant-associated () osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (FeO) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related tibial infection rabbit model, we evaluated its antibacterial performance . RNA transcriptome sequencing demonstrated that BSG + 5%FeO enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%FeO upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) . Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-β1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1β) among macrophages. CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%FeO + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of osteomyelitis. Further investigations will focus on the biosafety and biological mechanism of this scaffold within infectious microenvironment.
种植体相关()骨髓炎是骨科领域面临的一项严峻挑战。虽然载抗生素骨水泥是治疗骨髓炎的一种标准化方法,但在根除葡萄球菌脓肿群落(SACs)以及骨细胞-陷窝小管网络(OLCN)内的细菌和修复骨缺损方面存在不足。为解决这些局限性,我们开发了一种结合了三氧化二铁(FeO)的硼硅酸盐生物活性玻璃(BSG)磁性支架,以增强抗菌效果和骨修复能力。我们对该支架在有无交变磁场(AMF)情况下的骨诱导、免疫调节、抗菌性能及热响应进行了全面评估。利用成熟的种植体相关胫骨感染兔模型,我们评估了其抗菌性能。RNA转录组测序表明,BSG + 5%FeO增强了对细菌的免疫反应,并促进了间充质干细胞(MSCs)的成骨分化和矿化。值得注意的是,BSG + 5%FeO上调了MSCs中NOD样受体和TNF途径的基因表达,同时增加了成骨因子(RUNX2、ALP和OCN)的表达。巨噬细胞的流式细胞术显示出向M2极化的效应,同时巨噬细胞中抗炎基因(TGF-β1和IL-1Ra)上调,促炎基因(IL-6和IL-1β)下调。CT成像显示,在42天时,接受BSG + 5%FeO + AMF治疗的兔子未出现骨溶解和骨膜反应。组织学分析表明,到第42天时,OLCN内的SACs和细菌得到了完全控制,同时有新骨形成,这表明骨髓炎得到了有效控制。进一步的研究将聚焦于该支架在感染微环境中的生物安全性和生物学机制。