A Tensioned Human Skin Explant Model Used for Preliminary Assessment of Chemexfoliant-Stimulated Bioeffects

Michael J. Conneely , Jin Namkoong , Francis Allison , S. Kyoko Hirata Tsutsumi , Dominic Grussu , Ryan Willis , Kyle Henderson , Paul A. Campbell , Melissa Moy , Ewelina Lesniak , Joanna Wu , Robyn P. Hickerson
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Abstract

A tensioned ex vivo full-thickness human skin explant platform was used to assess the bioeffects arising from application of several commercial chemexfoliation agents. Although such treatments are well-established, and improved understanding of the underlying mechanistic processes continues to emerge, research into the optimum treatments for specific skin types/conditions is still needed for enhanced efficacy while minimizing recovery time. The 3 commercial chemexfoliation agents employed all contained trichloroacetic acid at well-defined concentrations (6, 10, and 20%) and were applied to the explants’ stratum corneum. Subsequently, measurements of dermal remodeling factors (COL1A1, ELN, HAS2, HAS3, and procollagen type I) and inflammatory marker (IL-1b) were undertaken using qPCR and immunofluorescent analyses. Statistical analysis of these data facilitated the establishment of benchmarking biological responses to these trichloroacetic acid–containing agents against untreated controls. The performance of an innovative trichloroacetic acid–free chemexfoliation agent was then measured and, upon comparison with the previous benchmarking data, indicated that dermal remodeling factors could be upregulated in fashion comparable with that of the trichloroacetic acid–containing agents but with significant suppression of inflammatory response. Our measurements thus underscore the promise of the tensioned explant over prolonged study periods and also that potentially valuable insights to guide preclinical strategies may be forthcoming from the protocol developed.
用于初步评估化纤刺激生物效应的拉伸人体皮肤切口模型
使用张力体外全厚人体皮肤外植体平台来评估应用几种商用化学去角质剂所产生的生物效应。虽然此类治疗方法已得到广泛认可,而且人们对其基本机理过程的了解也在不断加深,但仍需研究针对特定皮肤类型/条件的最佳治疗方法,以提高疗效,同时最大限度地缩短恢复时间。所采用的 3 种商用化学去角质剂都含有浓度明确的三氯乙酸(6%、10% 和 20%),并将其涂在外植体的角质层上。随后,使用 qPCR 和免疫荧光分析法测量了真皮重塑因子(COL1A1、ELN、HAS2、HAS3 和 I 型胶原)和炎症标志物(IL-1b)。对这些数据的统计分析有助于对照未处理的对照组,确定对这些含三氯乙酸制剂的生物反应的基准。然后,对一种创新的不含三氯乙酸的化学去死皮剂的性能进行了测定,并与之前的基准数据进行了比较,结果表明真皮重塑因子的上调方式与含三氯乙酸的制剂相当,但炎症反应明显受到抑制。因此,我们的测量结果表明,在长时间的研究过程中,张力外植体具有良好的前景,而且所制定的方案可能会为临床前策略提供有价值的指导。
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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CiteScore
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