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一种负载抗菌肽的交联涂层,用于镁合金骨科植入物的腐蚀控制、早期抗菌和后续成骨促进。

A cross-linked coating loaded with antimicrobial peptides for corrosion control, early antibacterial, and sequential osteogenic promotion on a magnesium alloy as orthopedic implants.

作者信息

Zhang Hao, Zhang Peng, Shen Xiaolong, Han Jiaping, Wang Haibo, Qin Haotian, Wang Binbin, Qian Junyu, Udduttula Anjaneyulu, Luo Rifang, Zhao Kexin, Wang Yunbing, Chen Yingqi

机构信息

Institute of Vanadium and Titanium, Panzhihua University, Panzhihua, 617000, PR China.

Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, PR China.

出版信息

Acta Biomater. 2025 Jan 24;193:604-622. doi: 10.1016/j.actbio.2024.12.046. Epub 2024 Dec 21.

DOI:10.1016/j.actbio.2024.12.046
PMID:39716540
Abstract

Magnesium (Mg)-based alloys have been recognized as desirable biodegradable materials for orthopedic implants. However, their clinical application has been limited by rapid degradation rates, insufficient antibacterial and osteogenic-promotion properties. Herein, a MgF priming layer was first constructed on AZ31 surface. Then, dopamine and polyphenols (EGCG) were cross-linked onto this AZ31-F surface to promote osteogenesis and further enhance corrosion protection, followed by chemical grafting of antimicrobial peptides (AMPs) via Michael-addition and Schiff-base reaction to confer antibacterial properties. In vitro electrochemical corrosion tests showed that i of AZ31-FE/AMPs (4.36×10 A/cm) is two orders of magnitude lower than that of AZ31 (4.17×10 A/cm). In vitro immersion degradation showed that AZ31-FE/AMPs exhibited the lowest hydrogen release (2.38 mL) after 400 h immersion with the lowest hydrogen evolution rate among them. Further, AZ31-FE/AMPs displayed inhibitory effects against S. aureus and E. coil in the initial stage and even after 7 days immersion in PBS (antibacterial rate > 85 %). AZ31-FE/AMPs promoted ALP secretion and calcium nodule formation in MC3T3-E1 cells. Transcriptome sequencing results indicated that osteogenic promotion mechanism of AZ31-FE/AMPs in MC3T3-E1 may involve the PI3K-Akt signalling pathway. Further, AZ31-FE/AMPs enhanced new bone formation when implanted in a rat femoral bone defect model. This coating strategy addresses initial antibacterial and later osteogenesis needs based on the corrosion control, which is crucial for the surface design of Mg-based implants. STATEMENT OF SIGNIFICANCE: It is critical for magnesium-based orthopedic implants to achieve sequential functions in the bone repair process while controlling an appropriate degradation rate. A MgF priming layer/phenolic-amine grafted AMPs (antimicrobial peptides) duplex coating was constructed on AZ31 surface in this study. The MgF layer provided a basic corrosion protection to magnesium substrate, and dopamine and polyphenols (EGCG) were then cross-linked to the MgF pretreated AZ31 to promote osteogenesis and enhance corrosion resistance, followed by chemical grafting of AMPs to confer antibacterial property. This strategy effectively meets the initial need for infection resistance and later osteogenic promotion on the basis of controlling the substrate corrosion rate, thus holding significant implications for the surface design of magnesium-based implants.

摘要

镁(Mg)基合金已被公认为是用于骨科植入物的理想可生物降解材料。然而,它们的临床应用受到快速降解速率、抗菌和成骨促进性能不足的限制。在此,首先在AZ31表面构建了一层MgF预处理层。然后,多巴胺和多酚(表没食子儿茶素,EGCG)交联到该AZ31-F表面以促进成骨并进一步增强腐蚀防护,随后通过迈克尔加成反应和席夫碱反应对抗菌肽(AMPs)进行化学接枝以赋予抗菌性能。体外电化学腐蚀试验表明,AZ31-FE/AMPs的腐蚀电流密度(4.36×10⁻⁵ A/cm²)比AZ31(4.17×10⁻³ A/cm²)低两个数量级。体外浸泡降解试验表明,AZ31-FE/AMPs在浸泡400小时后氢气释放量最低(2.38 mL),且析氢速率最低。此外,AZ31-FE/AMPs在初始阶段以及在PBS中浸泡7天后对金黄色葡萄球菌和大肠杆菌均显示出抑制作用(抗菌率>85%)。AZ31-FE/AMPs促进了MC3T3-E1细胞中碱性磷酸酶(ALP)的分泌和钙结节的形成。转录组测序结果表明,AZ31-FE/AMPs在MC3T3-E1细胞中的成骨促进机制可能涉及PI3K-Akt信号通路。此外,AZ31-FE/AMPs植入大鼠股骨骨缺损模型后增强了新骨形成。这种涂层策略基于腐蚀控制满足了初始抗菌和后期成骨的需求,这对于镁基植入物的表面设计至关重要。

重要性声明

对于镁基骨科植入物而言,在控制适当降解速率的同时在骨修复过程中实现序贯功能至关重要。本研究在AZ31表面构建了MgF预处理层/酚胺接枝抗菌肽(AMPs)双涂层。MgF层为镁基体提供了基本的腐蚀防护,然后多巴胺和多酚(EGCG)交联到经MgF预处理的AZ31上以促进成骨并增强耐腐蚀性,随后通过AMPs的化学接枝赋予抗菌性能。该策略在控制基体腐蚀速率的基础上有效地满足了初期抗感染和后期成骨促进的需求,因此对镁基植入物的表面设计具有重要意义。

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