氧化铈纳米酶-甲基丙烯酸酐化明胶水凝胶在小鼠全层皮肤缺损感染创面修复中的作用  

Effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride hydrogel in the repair of infected full-thickness skin defect wounds in mice

作　　者：顾雅男 徐翔昊 王彦平 李宇韬 梁振 余州 彭毅志 宋保强 Gu Ya'nan;Xu Xianghao;Wang Yanpin:;Li Yutao;Liang Zhen;Yu Zhou;Peng Yizhi;Song Baoqiang(Xi'an Medical University,Xi'an 710021,China;Department of Plastic Surgery,the First Affiliated Hospital,Air Force Medical University,Xi'an 710032,China;Institute of Burn Research,State Key Laboratory of Trauma and Chemical Poisoning,the First Affiliated Hospital of Army Medical University(the Third Military Medical University),Chongqing 400038,China)

机构地区：[1]西安医学院,西安710021 [2]空军军医大学第一附属医院整形科,西安710032 [3]陆军军医大学(第三军医大学)第一附属医院全军烧伤研究所,创伤与化学中毒全国重点实验室,重庆400038

出　　处：《中华烧伤与创面修复杂志》2024年第2期131-140,共10页Chinese Journal of Burns And Wounds

基　　金：陕西省科技厅一般项目(2020SF-179)。

摘　　要：目的探讨氧化铈纳米酶-甲基丙烯酸酐化明胶(GelMA)水凝胶(以下简称复合水凝胶)在小鼠全层皮肤缺损感染创面修复中的作用。方法该研究为实验研究。采用水热法制备粒径为(116±9)nm的氧化铈纳米酶,同时制备具有多孔网状结构且成胶性能良好的GelMA水凝胶。筛选出25μg/mL氧化铈纳米酶可明显促进人皮肤成纤维细胞增殖和具有较高的超氧化物歧化酶活性,将其加入GelMA水凝胶中制备复合水凝胶。计算用磷酸盐缓冲液(PBS)浸泡3、7 d后复合水凝胶中氧化铈纳米酶的释放百分比。将小鼠红细胞悬液分为用相应溶液处理的PBS组、Triton X-100组、氧化铈纳米酶组、GelMA水凝胶组及复合水凝胶组,利用酶标仪检测处理1 h后红细胞的溶血情况。测定用PBS、氧化铈纳米酶、GelMA水凝胶及复合水凝胶培养耐甲氧西林金黄色葡萄球菌(MRSA)和大肠埃希菌2 h后的细菌浓度。以上实验样本数均为3。取24只8周龄雄性BALB/c小鼠,在背部对称位置各制备1个用MRSA感染的全层皮肤缺损创面。将小鼠分为不进行药物干预的对照组及滴加相应溶液的氧化铈纳米酶组、GelMA水凝胶组和复合水凝胶组,每组6只小鼠。观察伤后3、7、14 d创面愈合情况并测量伤后3、7 d剩余创面面积(样本数为5)。取小鼠伤后3 d创面分泌物,检测MRSA的浓度(样本数为3),采用激光散斑血流成像系统观测小鼠伤后5 d创面血流灌注量(样本数为6)。伤后14 d,取小鼠创面组织,行苏木精-伊红染色观察新生上皮情况,行Masson染色观察胶原情况(样本数均为3)。结果浸泡3、7 d后,复合水凝胶中氧化铈纳米酶释放百分比分别约为39%、75%。处理1 h后,与Triton X-100组比较,PBS组、GelMA水凝胶组、氧化铈纳米酶组及复合水凝胶组红细胞溶血程度均明显下降(P<0.05)。与用PBS培养比较,用氧化铈纳米酶、GelMA水凝胶、复合水凝胶培养2 h的MRSA、大肠埃希菌浓Objective To investigate the effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride(GelMA)hydrogel(hereinafter referred to as composite hydrogel)in the repair of infected full-thickness skin defect wounds in mice.Methods This study was an experimental study.Cerium oxide nanoenzyme with a particle size of(116±9)nm was prepared by hydrothermal method,and GelMA hydrogel with porous network structure and good gelling performance was also prepared.The 25μg/mL cerium oxide nanoenzyme which could significantly promote the proliferation of human skin fibroblasts and had high superoxide dismutase activity was screened out.It was added to GelMA hydrogel to prepare composite hydrogel.The percentage of cerium oxide nanoenzyme released from the composite hydrogel was calculated after immersing it in phosphate buffer solution(PBS)for 3 and 7 d.The red blood cell suspension of mice was divided into PBS group,Triton X-100 group,cerium oxide nanoenzyme group,GelMA hydrogel group,and composite hydrogel group,which were treated with corresponding solution.The hemolysis of red blood cells was detected by microplate reader after 1 h of treatment.The bacterial concentrations of methicillin-resistant Staphylococcus aureus(MRSA)and Escherichia coli were determined after being cultured with PBS,cerium oxide nanoenzyme,GelMA hydrogel,and composite hydrogel for 2 h.The sample size in all above experiments was 3.Twenty-four 8-week-old male BALB/c mice were taken,and a full-thickness skin defect wound was prepared in the symmetrical position on the back and infected with MRSA.The mice were divided into control group without any drug intervention,and cerium oxide nanoenzyme group,GelMA hydrogel group,and composite hydrogel group applied with corresponding solution,with 6 mice in each group.The wound healing was observed on 3,7,and 14 d after injury,and the remaining wound areas on 3 and 7 d after injury were measured(the sample size was 5).The concentration of MRSA in the wound exudation of mice on 3 d after injury was measured(t

关 键 词：生物相容性材料 水凝胶 感染 氧化铈纳米酶 甲基丙烯酸酐化明胶 创面修复 

分 类 号：R318.08[医药卫生—生物医学工程]