Jeyapalina Sujee, Colombo John S, Beck James P, Agarwal Jayant P, Schmidt Linda A, Bachus Kent N
Division of Plastic Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah.
Research, Department of Veterans Affairs Medical Center, Salt Lake City, Utah.
J Biomed Mater Res B Appl Biomater. 2020 Feb;108(2):527-537. doi: 10.1002/jbm.b.34409. Epub 2019 May 10.
Epidermal downgrowth around percutaneous devices produce sinus tracts, which then accumulate bacteria becoming foci of infection. This mode to failure is epidermal-centric, and is accelerated by changes in the chemokines and cytokines of the underlying periprosthetic granulation tissue (GT). In order to more fully comprehend the mechanism of downgrowth, in this 28-day study, percutaneous devices were placed in 10 Zucker diabetic fatty rats; 5 animals were induced with diabetes mellitus II (DM II) prior to the surgery and 5 animals served as a healthy, nondiabetic cohort. At necropsy, periprosthetic tissues were harvested, and underwent histological and polymerase chain reaction (PCR) studies. After isolating GTs from the surrounding tissue and extracting ribonucleic acids, PCR array and quantitative-PCR (qPCR) analyses were carried-out. The PCR array for 84 key wound-healing associated genes showed a five-fold or greater change in 31 genes in the GTs of healthy animals compared to uninjured healthy typical skin tissues. Eighteen genes were overexpressed and these included epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR). Thirteen genes were underexpressed. When GTs of DM II animals were compared to healthy animals, there were 8 genes overexpressed and 25 genes underexpressed; under expressed genes included EGF and EGFR. The qPCR and immunohistochemistry data further validated these observations. Pathway analysis of genes up-regulated 15-fold or more indicated two, EGFR and interleukin-10, centric clustering effects. It was concluded that EGFR could be a key player in exacerbating the epidermal downgrowth, and might be an effective target for preventing downgrowth.
经皮装置周围的表皮向下生长会形成窦道，窦道随后会积聚细菌，成为感染病灶。这种失效模式以表皮为中心，并且会因假体周围肉芽组织（GT）中趋化因子和细胞因子的变化而加速。为了更全面地理解向下生长的机制，在这项为期28天的研究中，将经皮装置植入10只Zucker糖尿病肥胖大鼠体内；5只动物在手术前诱发了II型糖尿病（DM II），另外5只动物作为健康的非糖尿病对照组。尸检时，采集假体周围组织，并进行组织学和聚合酶链反应（PCR）研究。从周围组织中分离出GT并提取核糖核酸后，进行PCR阵列和定量PCR（qPCR）分析。针对84个关键伤口愈合相关基因的PCR阵列显示，与未受伤的健康典型皮肤组织相比，健康动物GT中的31个基因有五倍或更大的变化。18个基因过度表达，其中包括表皮生长因子（EGF）和表皮生长因子受体（EGFR）。13个基因表达不足。将DM II动物的GT与健康动物的GT进行比较时，有8个基因过度表达，25个基因表达不足；表达不足的基因包括EGF和EGFR。qPCR和免疫组织化学数据进一步证实了这些观察结果。对上调15倍或更多的基因进行通路分析表明有两个以EGFR和白细胞介素-10为中心的聚类效应。得出的结论是，EGFR可能是加剧表皮向下生长的关键因素，并且可能是预防向下生长的有效靶点。
