吉林大学学报(医学版)2024,Vol.50Issue(1) :106-112.DOI:10.13481/j.1671-587X.20240113

负载ZIF-8的GelMA水凝胶制备及其药物缓释性能和抑菌作用评价

Preparation of GelMA hydrogel loaded with ZIF-8 and evaluation of drug sustained release and antibacterial effect

姜孔昭 李驰宇 罗云纲 刘志辉
吉林大学学报(医学版)2024,Vol.50Issue(1) :106-112.DOI:10.13481/j.1671-587X.20240113

负载ZIF-8的GelMA水凝胶制备及其药物缓释性能和抑菌作用评价

Preparation of GelMA hydrogel loaded with ZIF-8 and evaluation of drug sustained release and antibacterial effect

姜孔昭 1李驰宇 2罗云纲 3刘志辉1
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作者信息

  • 1. 吉林大学口腔医院修复科, 吉林 长春 130021
  • 2. 吉林大学第二医院骨科,吉林 长春 130022
  • 3. 吉林大学第一医院净月分院口腔科,吉林 长春 130117
  • 折叠

摘要

目的:制备一种含沸石咪唑类骨架材料8(ZIF-8)的复合光交联水凝胶,评价其体外细胞毒性、药物释放能力和抗菌性能.方法:采用水热法合成 ZIF-8 颗粒,扫描电子显微镜(SEM)观察 ZIF-8 颗粒微观形态表现.将 ZIF-8 颗粒以质量分数 0.2%的比例与甲基丙烯酸酐化明胶(GelMA)混合获得复合水凝胶 GelMA-Z.采用原子吸收光谱法检测各时间点 GelMA-Z 中锌离子(Zn2+)累计释放量.NIH-3T3 细胞分为对照组、GelMA 组和GelMA-Z组,将GelMA和GelMA-Z与 NIH-3T3 细胞共培养 1、3和 7 d,采用 CCK-8 法检测各组细胞存活率.大肠杆菌(E.coli)和金黄色葡萄球菌(S.aureus)分为对照组、GelMA 组和GelMA-Z组,将 GelMA 和 GelMA-Z 分别与E.coli 和S.aureus 共培养6、12和 24 h,采用酶标仪检测不同时间点各组细菌活性,采用平板抑菌实验和活/死细菌染色实验检测各组细菌菌落形成情况和活/死细菌染色情况.结果:SEM 观察,采用水热法合成的 ZIF-8 颗粒具有均匀的粒径.原子吸收光谱法检测,GelMA-Z 中 Zn2+在 1 d 内呈突释阶段后缓慢释放,7 d 左右达到平衡.与对照组比较,1、3和 7 d 时GelMA 组和 GelMA-Z 组细胞存活率均大于 90%,差异无统计学意义(P>0.05).酶标仪检测菌液活性,与细菌共培养 6、12和 24 h时,与对照组和 GelMA 组比较,GelMA-Z 组 E.coli 和 S.aureus 活性明显降低(P<0.05).平板抑菌实验,GelMA-Z 组中菌液涂布后形成的菌落数明显少于对照组和 GelMA 组.活/死细菌染色实验,GelMA-Z 组存在大量红色荧光染色的死细菌,对照组和 GelMA 组中则为大量绿色荧光染色的活细菌.结论:负载 ZIF-8的 GelMA水凝胶可实现原位光交联,具有良好的 Zn2+释放能力和抗菌性,是一种可用于感染伤口治疗的新型水凝胶敷料.

Abstract

objective:To prepare a composite photocrosslinked hydrogel containing zeolite imidazole framework-8(ZIF-8),and to evaluate its in vitro cytotoxicity,drug release capability,and antimicrobial propertie.Methods:The ZIF-8 particles were synthesized by hydrothermal method,and the microstructure characteristic was observed under scanning electron microscope(SEM).The particles were mixed with the gelatin methacryloyl(GelMA)with the mass fraction of 0.2%to obtain the composite hydrogel GelMA-Z.The atomic absorption spectroscope was used to detect the cumulative zinc ion(Zn2+)release amounts in GelMA-Z at different time points.The NIH-3T3 cells were co-cultured with GelMA-Z for 1,3,and 7 d;the viabilities of the cells in various groups were detected by CCK-8 assay;the GelMA-Z was co-cultured with Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)for 6,12,and 24 h and divided into control group,GelMA group,and GelMA-Z group.The bacterial activities of the cells in various groups at different time points were detected by microplate reader;the bacterial formation and the presence of live/dead becterial staining condition were detected by plate antibacterial experiment and live/dead bacterial staining method.Results:The SEM observation results showed that the hydrothermally synthesized ZIF-8 particles had the uniform particle sizes.The atomic absorption spectroscope results showed that Zn2+ in GelMA-Z showed an initial burst phase within 1 d,followed by a slow release,and reached the equilibrium around 7 d.Compared with control group,the viabilities the cells in GelMA group and GelMA-Z group were above 90%on the 1st,3rd,and 7th days,but there was no significant difference(P>0.05).The bacterial activity detection results showed that when co-cultured with bacteria for 6,12,and 24 h,compared with control group and GelMA group,the bacterial activities of the E.coli and S.aureus in GelMA-Z group were decreased(P<0.05).The plate antibacterial experiment results showed that the number of bacterial formation in GelMA-Z group was fewer than those in control group and GelMA group.The live/dead bacterial staining results showed that in GelMA-Z group,there was a large number of red fluorescence stained dead bacteria;in control group and GelMA group,there was a large number of green fluorescence stained live bacteria.Conclusion:The GelMA hydrogel loaded with ZIF-8 particles can achieve the in situ photocrosslinking and possesses good Zn2+ release capability and antimicrobial activity,and it is a novel hydrogel dressing for treatment of the infected wounds.

关键词

含沸石咪唑类骨架材料8/甲基丙烯酸酐化明胶/水凝胶/感染伤口/抗菌性能

Key words

Zeolite imidazole framework-8/Gelatin methacryloyl/Hydrogel/Infected wound/Antibacterial property

引用本文复制引用

基金项目

吉林省科技厅医药健康专项项目(20200708107YY)

吉林省科技厅重点研发项目(20220204124YY)

出版年

2024
吉林大学学报(医学版)
吉林大学

吉林大学学报(医学版)

CSTPCDCSCD北大核心
影响因子:0.909
ISSN:1671-587X
参考文献量25
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