聚醚醚酮与柠檬酸盐增强铜的内流促进骨生成,血管生成和细菌引发的抗菌能力

Jianglong Yan, D. Xia, Pa N. Xiong, Yangyang Li, Wenhao Zhou, Qiyao Li, Pei Wang, Qiyao Li, Yufeng Zheng, Yan Cheng
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引用次数: 9

摘要

设计良好的聚醚醚酮(PEEK)种植体涂层可以为其提供足够的支撑,以克服骨整合不足和高感染率等关键的医学挑战。在此,我们利用聚多巴胺(PDA)和柠檬酸铜纳米团簇的共沉积,在多孔PEEK上构建了ph响应涂层,用于协同骨再生、血管形成和抗感染。具体来说,这种PDA涂层在较低的pH值下释放出高剂量的铜和柠檬酸盐,增加了细胞内铜含量,促进了活性氧的产生,严重损害了蛋白质,导致93%的浮游细菌被杀死,附着细菌被根除。在pH为7.4时,铜和柠檬酸盐的释放缓慢而持续,协同增强了体外Ad-MSC的血管形成潜力和骨分化。在兔胫骨植入6周和12周后,显微ct评估和组织学分析一致强调该PDA涂层能够增加涂层PEEK种植体附近的新骨形成,并增强骨-种植体界面整合。这些结果被证明与柠檬酸盐促进铜2倍流入细胞的协同效应有关,这不仅增强了细菌杀灭能力,而且还促进了植入物的骨再生。本研究提供了在控制感染的同时促进骨融合的有效方法,具有巨大的临床应用价值,可以解决当前骨科面临的挑战。
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Polyetheretherketone with Citrate Potentiated Influx of Copper Boosts Osteogenesis, Angiogenesis, and Bacteria-Triggered Antibacterial Abilities
Abstract A well designed coating for polyetheretherketone (PEEK) implants can provide enough support to overcome crucial medical challenges, which are insufficient osseointegration and high rate of infection. Herein, we utilize the co-deposition of polydopamine (PDA) and copper-citrate nanoclusters to construct a pH-responsive coating on porous PEEK for synergistic bone regeneration, vascular formation and anti-infection. Specifically, this PDA coating released high dose of copper and citrate at lower pH value, which increased intracellular copper content, boosted production of reactive oxygen species and severe damage of protein, leading to killing of 93 % planktonic bacterial and eradication of adherent bacteria. At pH of 7.4, the release of copper and citrate were in a slow and sustained behavior, synergistically enhanced vascular formation potential and osteodiffereration of Ad-MSC in vitro. After implanted in rabbit tibia for 6 and 12 weeks, the micro-CT evaluation and histological analysis consistently highlighted the ability of this PDA coating to increase new bone formation adjacent to coated PEEK implant and enhance bone-implant interfacial integration. These results were proven to be related to the synergistic effect that citrate facilitated a 2-fold influx of copper into cells, which not only enhanced the bacteria-killing ability but also encouraged bone regeneration of implants. This present work provides an effective method to control infections while promoting osseointegration simultaneously, which will show tremendous clinical application and can be a solution to current challenges facing orthopedics.
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