Jahanshahi Maryam, Hamdi David, Godau Brent, Samiei Ehsan, Sanchez-Lafuente Carla Liria, Neale Katie J, Hadisi Zhina, Dabiri Seyed Mohammad Hossein, Pagan Erik, Christie Brian R, Akbari Mohsen
Laboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada.
Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada.
Micromachines (Basel). 2020 Feb 23;11(2):227. doi: 10.3390/mi11020227.
Wound infection is a major clinical challenge that can significantly delay the healing process, can create pain, and requires prolonged hospital stays. Pre-clinical research to evaluate new drugs normally involves animals. However, ethical concerns, cost, and the challenges associated with interspecies variation remain major obstacles. Tissue engineering enables the development of in vitro human skin models for drug testing. However, existing engineered skin models are representative of healthy human skin and its normal functions. This paper presents a functional infected epidermis model that consists of a multilayer epidermis structure formed at an air-liquid interface on a hydrogel matrix and a three-dimensionally (3D) printed vascular-like network. The function of the engineered epidermis is evaluated by the expression of the terminal differentiation marker, filaggrin, and the barrier function of the epidermis model using the electrical resistance and permeability across the epidermal layer. The results showed that the multilayer structure enhances the electrical resistance by 40% and decreased the drug permeation by 16.9% in the epidermis model compared to the monolayer cell culture on gelatin. We infect the model with to study the inflammatory response of keratinocytes by measuring the expression level of pro-inflammatory cytokines (interleukin 1 beta and tumor necrosis factor alpha). After 24 h of exposure to , the level of IL-1β and TNF-α in control samples were 125 ± 78 and 920 ± 187 pg/mL respectively, while in infected samples, they were 1429 ± 101 and 2155.5 ± 279 pg/mL respectively. However, in ciprofloxacin-treated samples the levels of IL-1β and TNF-α without significant difference with respect to the control reached to 246 ± 87 and 1141.5 ± 97 pg/mL respectively. The robust fabrication procedure and functionality of this model suggest that the model has great potential for modeling wound infections and drug testing.
伤口感染是一项重大的临床挑战，它会显著延迟愈合过程，引发疼痛，并需要延长住院时间。评估新药的临床前研究通常涉及动物。然而，伦理问题、成本以及与种间差异相关的挑战仍然是主要障碍。组织工程学使得开发用于药物测试的体外人体皮肤模型成为可能。然而，现有的工程皮肤模型仅代表健康的人体皮肤及其正常功能。本文提出了一种功能性感染表皮模型，该模型由在水凝胶基质上的气液界面形成的多层表皮结构和三维（3D）打印的血管样网络组成。通过终末分化标志物丝聚蛋白的表达以及利用跨表皮层的电阻和渗透率评估表皮模型的屏障功能，来评价工程表皮的功能。结果表明，与明胶上的单层细胞培养相比，多层结构使表皮模型的电阻提高了40%，药物渗透率降低了16.9%。我们用[具体物质未给出]感染该模型，通过测量促炎细胞因子（白细胞介素1β和肿瘤坏死因子α）的表达水平来研究角质形成细胞的炎症反应。在暴露于[具体物质未给出]24小时后，对照样品中IL-1β和TNF-α的水平分别为125±78和920±187 pg/mL，而在感染样品中，它们分别为1429±101和2155.5±279 pg/mL。然而，在环丙沙星处理的样品中，IL-1β和TNF-α的水平分别达到246±87和1141.5±97 pg/mL，与对照相比无显著差异。该模型强大的构建过程和功能表明，该模型在模拟伤口感染和药物测试方面具有巨大潜力。
