The Dorsal Skinfold Chamber as a New Tympanic Membrane Wound Healing Model: Intravital Insights into the Pathophysiology of Epithelialized Wounds.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Daniel Strüder, Christoph Lachmann, Sara Maria van Bonn, Eberhard Grambow, Sebastian P Schraven, Robert Mlynski, Brigitte Vollmar
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引用次数: 0

Abstract

Background: Tympanic membrane perforations (TMPs) are a common complication of trauma and infection. Persisting perforations result from the unique location of the tympanic membrane. The wound is surrounded by air of the middle ear and the external auditory canal. The inadequate wound bed, growth factor, and blood supply lead to circular epithelialization of the perforation's edge and premature interruption of defect closure. Orthotopic animal models use mechanical or chemical tympanic membrane laceration to identify bioactive wound dressings and overcome premature epithelialization. However, all orthotopic models essentially lack repetitive visualization of the biomaterial-wound interface. Therefore, recent progress in 3D printing of customized wound dressings has not yet been transferred to the unique wound setup of the TMP. Here, we present a novel application for the mice dorsal skinfold chamber (DSC) with an epithelialized full-thickness defect as TMP model.

Methods: A circular 2-mm defect was cut into the extended dorsal skinfold using a biopsy punch. The skinfold was either perforated through both skin layers without prior preparation or perforated on 1 side, following resection of the opposing skin layer. In both groups, the wound was sealed with a coverslip or left unclosed (n = 4). All animals were examined for epithelialization of the edge (histology), size of the perforation (planimetry), neovascularization (repetitive intravital fluorescence microscopy), and inflammation (immunohistology).

Results: The edge of the perforation was overgrown by the cornified squamous epithelium in all pre-parations. Reduction in the perforation's size was enhanced by application of a coverslip. Microsurgical preparation before biopsy punch perforation and sealing with a coverslip enabled repetitive high-quality intravital fluorescence microscopy. However, spontaneous reduction of the perforation occurred frequently. Therefore, the direct biopsy punch perforation without microsurgical preparation was favorable: spontaneous reduction did not occur throughout 21 days. Moreover, the visualization of the neovascularization was sufficient in intravital microscopy.

Conclusions: The DSC full-thickness defect is a valuable supplement to orthotopic TMP models. Repetitive intravital microscopy of the epithelialized edge enables investigation of the underlying pathophysiology during the transition from the inflammation to the proliferation phase of wound healing. Using established analysis procedures, the present model provides an effective platform for the screening of bioactive materials and transferring progress in tissue engineering to the special conditions of tympanic membrane wound healing.

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背侧皮肤褶腔作为一种新的鼓膜伤口愈合模型:对上皮化伤口病理生理的活体观察。
背景:鼓膜穿孔(TMPs)是创伤和感染的常见并发症。持续穿孔是由于鼓膜的独特位置造成的。伤口被中耳和外耳道的空气包围。伤口床、生长因子和血液供应不足导致穿孔边缘的圆形上皮化和缺损闭合的过早中断。原位动物模型使用机械或化学鼓膜撕裂来识别生物活性伤口敷料并克服过早上皮化。然而,所有的原位模型基本上都缺乏生物材料-伤口界面的重复可视化。因此,最近3D打印定制伤口敷料的进展尚未转移到TMP的独特伤口设置。在此,我们提出了一种新的应用于具有上皮化全层缺陷的小鼠背皮肤褶腔(DSC)作为TMP模型。方法:采用活组织检查穿孔机在延长的背侧皮肤褶上切开一个2毫米的圆形缺损。在没有事先准备的情况下,皮褶在两层皮肤上穿孔,或者在切除对面皮肤层后在一侧穿孔。在两组中,伤口都用盖唇密封或不闭合(n = 4)。所有动物都检查了边缘的上皮化(组织学)、穿孔的大小(平面测量)、新生血管(重复活体荧光显微镜)和炎症(免疫组织学)。结果:穿孔边缘均被角化鳞状上皮覆盖。应用复盖可以减小射孔的尺寸。活检穿孔前的显微外科准备和盖盖封合使重复的高质量活体荧光显微镜成为可能。然而,穿孔的自发复位经常发生。因此,没有显微手术准备的直接活检穿孔是有利的:在21天内没有发生自发复位。此外,在活体显微镜下,新生血管的可视化是足够的。结论:DSC全层缺损是对原位TMP模型有价值的补充。在伤口愈合从炎症过渡到增殖阶段的过程中,对上皮化边缘的重复活体显微镜可以研究潜在的病理生理学。利用已建立的分析程序,本模型为生物活性材料的筛选和将组织工程的进展转移到鼓膜伤口愈合的特殊条件提供了有效的平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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