Determining the Biomechanical and Biological Response of Stretched Skin

 描述(申请人提供)：2013年，美国整形外科学会的会员仅为乳房再造就放置了68,607个组织扩张器。组织扩张术是一种拉伸皮肤以促进生长的过程，虽然多年来一直得到成功的利用，但并发症发生率仍然很高，特别是在头、颈和四肢等可招募的正常皮肤最少的区域。组织扩张的一个固有问题是，对皮肤拉伸所发生的分子事件和皮肤机械变化都没有完全了解。虽然细胞研究已经阐明了角质形成细胞和成纤维细胞中的一些机械转导途径，但组织对拉伸的反应的实际机制涉及复杂的相互作用，这些相互作用不能仅在细胞中复制。此外，皮肤生长对拉伸的反应比率还没有确定。为了充分阐明这些数据，需要一个既能进行生物力学评估又能进行生物评估的体内模型。我们假设，皮肤生长在拉伸最大的区域变化最大，这将与已知机械转导途径的基因表达和激活有关。我们建立的小型猪组织扩张模型是与斯坦福大学工程学和斯坦福大学合作的多学科合作成果 威斯康星州-密尔沃基，利用计算机化的3D分析，允许精确计算动物皮肤任何点的拉伸和表面积增长。我们将在四只小型猪的两个位置植入组织扩张器，每个扩张器将在不同的时间填充。采集这种拉伸的皮肤将有助于组织生长计算，以及组织学、免疫组织化学和基因表达分析。这些数据将与STRAGE相关联，以阐明生物力学和分子对变形力的反应的时间表。我们希望这些实验将使我们能够确定皮肤对拉伸的生长反应，以及确定与这种生长相关的分子事件的时间线。这些数据将用于进一步的研究，以确定固有的变化 在这些照射组织的路径中，还将提供即时的临床信息，以优化组织扩张的现有技术，特别是在类似捐赠者组织高度有限的区域，如头、颈部和四肢。

 DESCRIPTION (provided by applicant): In 2013, American Society of Plastic Surgeons members placed 68,607 tissue expanders for breast reconstruction alone. While tissue expansion, the process of stretching skin in order to increase growth, has been utilized successfully for many years, complication rates remain high, particularly in areas with minimal recruitable normal skin such as the head, neck and extremities. One of the inherent problems with tissue expansion is that both the molecular events and the skin mechanical changes that occur in response to skin stretch are incompletely understood. While cellular studies have elucidated some mechanotransduction pathways in keratinocytes and fibroblasts, the actual mechanism of tissue growth in response to stretch involves complex interactions that cannot be replicated in cells alone. Furthermore, the ratios of skin growth in response to stretch have not been determined. In order to fully elucidate these data, an in vivo model that allows both biomechanical and biologic evaluation is required. We hypothesize that skin growth varies and is maximal in areas of maximum stretch, and this will be correlated with gene expression and activation of known mechanotransduction pathways. Our established minipig model of tissue expansion is a collaborative, multidisciplinary effort with Stanford Engineering and the University of Wisconsin--‐ Milwaukee that utilizes computerized 3D analysis to allow the precise calculation of the stretch and surface area growth of any point of skin of the animal. We will implant tissue expanders at two sites in four minipigs, and each expander will be filled at different times. Harvest of this stretched skin will facilitate tissue growth calculations, as wellas histologic, immunohistochemically, and gene expression analysis. These data will be correlated to stretch to elucidate a timeline of the biomechanical and molecular response to deformational force. We expect that these experiments will allow us to determine skin's growth response to stretch, as well as to determine the timeline of molecular events that are altered in association with this growth. These data will be utilized for further studies to determine the inherent changes in these pathways in irradiated tissues, and will also offer immediate clinical information to optimize current techniques in tissue expansion, particularly in areas where like donor tissue is highly limited, such as the head, neck, and extremities.