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载铜金属有机骨架的壳聚糖基冷冻干燥高多孔敷料具有抗生物膜和促血管生成活性,可加速铜绿假单胞菌感染创面在大鼠体内的愈合。

Cu-MOF loaded chitosan based freeze-dried highly porous dressings with anti-biofilm and pro-angiogenic activities accelerated Pseudomonas aeruginosa infected wounds healing in rats.

机构信息

Interdisciplinary Research Center in Biomedical Materials (IRCBM), COMSATS University Islamabad, Lahore Campus, Defence Road off Raiwind Road, Lahore 54000, Pakistan; Department of Chemistry, Government College University Lahore, Pakistan.

Department of Chemistry, Government College University Lahore, Pakistan.

出版信息

Int J Biol Macromol. 2024 Jun;271(Pt 2):132443. doi: 10.1016/j.ijbiomac.2024.132443. Epub 2024 May 16.

Abstract

Metal-organic frameworks (MOFs)-based therapy opens a new area for antibiotic-drug free infections treatment. In the present study, chitosan membranes (CS) loaded with two concentrations of copper-MOF 10 mg/20 ml (Cu-MOF10/CS) & 20 mg/20 ml (Cu-MOF20/CS) were prepared by a simple lyophilization procedure. FTIR spectra of Cu-MOF10/CS and Cu-MOF20/CS dressings confirmed absence of any undesirable chemical changes after loading Cu-MOF. The SEM images of the synthesized materials (CS, Cu-MOF10/CS & Cu-MOF20/CS) showed interconnected porous structures. Cytocompatibility of the materials was confirmed by fibroblasts cells culturing and the materials were hemocompatible, with blood clotting index <5 %. Cu-MOF20/CS showed comparatively higher effective antibacterial activity against the tested strains; E. coli (149.2 %), P. aeruginosa (165 %) S. aureus (117.8 %) and MRSA (142 %) as compared to Amikacin, CS and Cu-MOF10/CS membranes. Similarly, Cu-MOF20/CS dressing significantly eradicated the biofilms; P. aeruginosa (37 %) and MRSA (52 %) respectively. In full thickness infected wound rat model, on day 23, Cu-MOF10/CS and Cu-MOF20/CS promoted wound healing up to 87.7 % and 82 % respectively. H&E staining of wounded tissues treated with Cu-MOF10/CS & Cu-MOF20/CS demonstrated enhanced neovascularization and re-epithelization along-with reduced inflammation, while trichrome staining exhibited increased collagen deposition. Overall, this study declares Cu-MOFs loaded chitosan dressings a multifunctional platform for the healing of infected wounds.

摘要

基于金属有机骨架(MOFs)的治疗为抗生素药物免费治疗感染开辟了一个新领域。在本研究中,通过简单的冷冻干燥程序制备了壳聚糖膜(CS)负载两种浓度的铜-MOF(10mg/20ml 的 Cu-MOF10/CS 和 20mg/20ml 的 Cu-MOF20/CS)。Cu-MOF10/CS 和 Cu-MOF20/CS 敷料的 FTIR 光谱证实负载 Cu-MOF 后没有发生任何不良的化学变化。合成材料(CS、Cu-MOF10/CS 和 Cu-MOF20/CS)的 SEM 图像显示出相互连接的多孔结构。通过成纤维细胞培养证实了材料的细胞相容性,并且材料具有良好的血液相容性,凝血指数<5%。与阿米卡星、CS 和 Cu-MOF10/CS 膜相比,Cu-MOF20/CS 对测试菌株表现出更高的有效抗菌活性;大肠杆菌(149.2%)、铜绿假单胞菌(165%)、金黄色葡萄球菌(117.8%)和耐甲氧西林金黄色葡萄球菌(142%)。同样,Cu-MOF20/CS 敷料显著消除了生物膜;铜绿假单胞菌(37%)和耐甲氧西林金黄色葡萄球菌(52%)。在全厚度感染伤口大鼠模型中,在第 23 天,Cu-MOF10/CS 和 Cu-MOF20/CS 分别促进伤口愈合至 87.7%和 82%。用 Cu-MOF10/CS 和 Cu-MOF20/CS 处理的受伤组织的 H&E 染色显示出增强的新生血管形成和再上皮化,同时炎症减少,而三色染色显示出增加的胶原蛋白沉积。总的来说,这项研究表明负载铜-MOF 的壳聚糖敷料是治疗感染性伤口的多功能平台。

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