Delayed wound healing in diabetic (db/db) mice with Pseudomonas aeruginosa biofilm challenge: a model for the study of chronic wounds.
Delayed wound healing in diabetic (db/db) mice with Pseudomonas aeruginosa biofilm challenge: a model for the study of chronic wounds.
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DOI：
10.1111/j.1524-475x.2010.00608.x
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Olerud JE
中科院分区：
文献类型：
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作者：
Zhao G;Hochwalt PC;Usui ML;Underwood RA;Singh PK;James GA;Stewart PS;Fleckman P;Olerud JE
慢性伤口是导致相当大的发病率和死亡率的主要临床问题。我们假设，慢性伤口愈合失败的一个重要因素是存在对抗生素具有抗性并免受宿主防御的微生物生物膜。研究慢性创伤的一个主要困难是缺乏合适的动物模型。本研究的目的是通过应用细菌生物膜在糖尿病小鼠中建立可重复的慢性伤口模型。在糖尿病（db/db）小鼠的背表面上产生6毫米穿孔活检伤口，随后在受伤后两天用铜绿假单胞菌（PAO 1）生物膜攻击，并用半封闭敷料覆盖两周。大多数对照伤口在伤后28天上皮化。相比之下，没有生物膜攻击的伤口闭合。组织学分析显示，在受攻击的伤口附近存在广泛的炎性细胞浸润、组织坏死和表皮增生-所有这些都是炎性不愈合伤口的指标。定量培养和透射电子显微镜检查表明，大多数细菌在伤口床上方的结痂中，而不是在伤口组织中。该模型是可重复的，允许局部皮肤伤口感染，而没有高死亡率，并表现出延迟的伤口愈合后，生物膜的挑战。该模型可为研究慢性创面中微生物生物膜的作用以及特异性生物膜治疗对创面愈合的影响提供一种方法。
Chronic wounds are a major clinical problem that leads to considerable morbidity and mortality. We hypothesized that an important factor in the failure of chronic wounds to heal was the presence of microbial biofilm resistant to antibiotics and protected from host defenses. A major difficulty in studying chronic wounds is the absence of suitable animal models. The goal of this study was to create a reproducible chronic wound model in diabetic mice by application of bacterial biofilm. Six millimeter punch biopsy wounds were created on the dorsal surface of diabetic (db/db) mice, subsequently challenged with Pseudomonas aeruginosa (PAO1) biofilms two days post-wounding, and covered with semi-occlusive dressings for two weeks. Most of the control wounds were epithelialized by 28 days post-wounding. In contrast, none of biofilm challenged wounds were closed. Histological analysis showed extensive inflammatory cell infiltration, tissue necrosis and epidermal hyperplasia adjacent to challenged wounds- all indicators of an inflammatory non-healing wound. Quantitative cultures and transmission electron microscopy demonstrated that the majority of bacteria were in the scab above the wound bed rather than in the wound tissue. The model was reproducible, allowed localized cutaneous wound infections without high mortality and demonstrated delayed wound healing following biofilm challenge. This model may provide an approach to study the role of microbial biofilms in chronic wounds as well as the effect of specific biofilm therapy on wound healing.