摘要
背景外伤或疾病导致的皮肤创伤可引发多种并发症甚至死亡。如何构建能有效促进止血、愈合和修复的创面敷料,是亟待解决的关键问题。目的观察羟丁基壳聚糖(hydroxybutyl chitosan,HBC)联合生物矿化硅(biosilica,BS)复合水凝胶敷料对小鼠皮肤全层创伤的修复效果。方法在20只9周龄雄性C57BL/6J小鼠背部的左右两侧分别制作直径6 mm的全层皮肤创伤模型,利用硅胶固定板固定,防止创面收缩。小鼠随机分为A、B两组。A组小鼠右侧创面为HBC/BS组,即实验组;A组小鼠左侧创面为空白对照组;B组小鼠右侧创面为羧甲基纤维素钠(carboxymethylcellulose sodium,CMC-Na)/丙二醇(propylene glycol,PG)组;B组小鼠左侧创面为HBC组。小鼠单笼饲养,所有创面均每3 d给予1次常规消毒处理并更换固定板。每次消毒后,空白对照创面直接覆盖透气透明膜,其余各组创面均给予对应的水凝胶药物200 mg,均匀涂布后覆盖透气透明膜。持续观察创面出血及愈合情况,在15 d和21 d时分别对各组半数小鼠创面组织取样,进行HE染色、Masson染色和BrdU免疫荧光染色,并检测创面组织中的羟脯氨酸含量。结果实验组在建模后3 d、6 d、9 d、12 d、15 d时的创面愈合率均显著高于空白对照组(P<0.01),在3 d、6 d、9 d时的愈合率显著高于CMC-Na/PG组(P<0.01),实验组创面愈合率在各时间点均与HBC组无统计学差异(P>0.05)。病理学观察提示,在建模后15 d和21 d时,实验组与HBC组的创面更接近正常皮肤的层次和结构,上皮组织被覆完整且结构致密,胶原纤维分布均匀、排列整齐有序,实验组的皮肤附属器分布密度和结构完整性优于其他各组。建模后15 d,实验组创面组织羟脯氨酸的含量高于空白对照组和CMC-Na/PG组(P<0.05),与HBC组差异无统计学意义(P>0.05);建模后21 d,各组差异无统计学意义(P>0.05)。结论HBC/BS水凝胶和HBC水凝胶相较于已应用于临床的CMC-Na/PG水凝胶,均有更好的促进创面愈合的效果,添加了BS的复合水凝胶可有效促进皮肤附属器的修复再生,相较于HBC水凝胶有更为全面的促修复愈合能力。
Background Skin wound caused by injury or disease can lead to multiple complications or even death.How to construct wound dressing that can effectively promote hemostasis,healing and repair is a key problem to be solved urgently.Objective To observe the effect of hydroxybutyl chitosan(HBC)combined with biosilica(BS)composite hydrogel dressing on the repair of fullthickness skin wound in mice.Methods Twenty 9-week-old male C57BL/6J mice were treated with full-thickness skin wound models of 6mm in diameter on the left and right sides of the back,which were fixed with silica gel plates to prevent wound contraction.The mice were randomly divided into group A and group B.The wounds on the right side of group A were HBC/BS group(experimental group).The left wounds of mice in group A were blank control group.The right wounds of mice in group B were carboxymethylcellulose sodium(CMC-Na)/propylene glycol(PG)group,and the left wounds of mice in group B were HBC group.Every mouse was raised in a single cage,and all wounds were routinely disinfected every 3 days and fixed plates were replaced.After disinfection,the blank control wounds were directly covered with breathable transparent film,while wounds in other groups were evenly coated with corresponding hydrogel drug for 200 mg,and then covered with breathable transparent film.Wound bleeding and healing in each group were continuously observed.Wound tissue samples were taken from half of the mice in each group at 15 d and 21 d.HE staining,Masson staining and BrdU immunofluorescence staining were performed,and the hydroxyproline content in wound tissue was detected.Results The wound healing rates of the experimental group were significantly higher than those of the blank control group at 3 d,6 d,9 d,12 d and 15 d after modeling(P<0.01),and were significantly higher than those of the CMC-Na/PG group at 3 d,6 d and 9 d(P<0.01).There was no significant difference in the wound healing rate between the experimental group and the HBC group at all time points(P>0.05).Pathological observation suggested that at 15 d and 21 d after modeling,the wound surface of the experimental group and the HBC group was closer to the structure of normal skin,the epithelium was intact and dense,and the collagen fibers were uniform and orderly.The distribution density and structural integrity of skin appendages in the experimental group were better than those in other groups.At 15 d after modeling,the hydroxyproline content of wound tissue in experimental group was higher than that in blank control group and CMC-Na/PG group(P<0.05),but there was no significant difference between experimental group and HBC group(P>0.05).At 21 d after modeling,there was no significant difference among groups(P>0.05).Conclusion Compared with CMC-Na/PG hydrogel that has been applied in clinical practice,HBC/BS hydrogels and HBC hydrogels have better effect on promoting wound healing.Composite hydrogel with BS can effectively promote the regeneration and repair of skin appendages,and it has a more comprehensive ability to promote wound repair and healing compared with HBC hydrogel.
作者
吕宁宇
李冀
赵之栋
王琪
白晓伟
傅仰木
李众利
LYU Ningyu;LI Ji;ZHAO Zhidong;WANG Qi;BAI Xiaowei;FU Yangmu;LI Zhongli(Chinese PLA Medical School,Beijing 100853,China;Department of Orthopedics,the Fourth Medical Center,Chinese PLA General Hospital,Beijing 100048,China;Department of Orthopedics,Hainan Hospital of Chinese PLA General Hospital,Sanya 572013,Hainan Province,China)
出处
《解放军医学院学报》
CAS
北大核心
2022年第5期563-569,共7页
Academic Journal of Chinese PLA Medical School
基金
国家自然科学基金-山东联合基金(U170620043)。
