797 Optimal tension facilitates wound healing in a full-thickness ex vivo human skin model
797 Optimal tension facilitates wound healing in a full-thickness ex vivo human skin model
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第797章 最佳张力促进全层离体人体皮肤模型中的伤口愈合
DOI：
10.1016/j.jid.2022.05.810
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发表时间：
2022
影响因子：
6.5
通讯作者：
Conneely M
中科院分区：
文献类型：
--
作者：
Conneely M
使用人体皮肤模型是研究皮肤生物学的一种广泛接受的方法。这些模型包括从人体细胞重建的器官系统以及基于废弃手术组织的模型。基于细胞的系统的设置和维护非常耗时，无法完全重现皮肤的分化结构，并且通常缺乏少量的皮肤细胞群。传统的全层皮肤模型是由手术期间收集的切除皮肤组织制成的，一旦离开身体，很快就会失去活力和对刺激做出反应的能力。牵引力平衡对于维持皮肤稳态至关重要，因此是调节组织结构和生理功能的重要因素。在这里，我们描述了一种基于张力的皮肤外植体模型，以解决人类皮肤模型未满足的需求，该模型即使在伤口反应和愈合等复杂的生物过程中也能可靠地模拟体内皮肤。这种基于张力的模型模拟了对激光烧蚀伤口的类似体内反应，在整个受伤皮肤样本中观察到角蛋白 17，而在无张力培养的皮肤中仅观察到极少的表达。此外，对伤口部位长达 3 周的观察表明，基底膜的重建高度依赖于张力的存在。对多种伤口愈合标记物的 qPCR 分析也显示，与在最佳张力下培养的皮肤相比，非张力皮肤对伤口的反应延迟和减弱。因此，应用优化的张力可以恢复皮肤固有的力学生物学，从而实现更像体内的行为，从而大大增加全层离体皮肤模型的实用性。利益冲突：MJC 和 RPH 是 Ten Bio Ltd 的创始人和董事，该公司专注于体外皮肤模型的开发。
The use of human skin models is a widely accepted approach for studying skin biology. These models include organotypic systems reconstructed from human cells as well as models based on discarded surgical tissue. Cell-based systems are time-consuming to set up and maintain, are unable to fully recapitulate the differentiated architecture of the skin, and typically lack minor skin cell populations. Traditional full-thickness skin models prepared from excised skin tissue collected during surgery quickly lose viability and the ability to respond to stimuli once off the body. Traction-force balance is essential for maintaining skin homeostasis and is, therefore, an important factor in regulating both tissue structure and physiological function. Here we describe a tension-based skin explant model to address the unmet need for a human skin model that reliably mimics in vivo skin even in complex biological processes such as wound response and healing. This tension-based model mimics an in vivo-like response to laser ablative wounding, with keratin 17 observed throughout the wounded skin sample, whereas only minimal expression is observed in skin cultured without tension. Additionally, observation of the wound sites for up to 3 weeks shows that reformation of the basement membrane is highly dependent on the presence of tension. qPCR analysis of a variety of wound healing markers also showed a delayed and diminished response to wounding in non-tensioned skin compared to skin cultured at optimal tension. Application of optimized tension can therefore restore skin’s inherent mechanobiology, enabling a more in vivo-like behavior, greatly increasing the utility of full-thickness ex vivo skin models. Conflict of interest: MJC and RPH are founders and directors of Ten Bio Ltd, a company focused on development of ex vivo skin models.