Determining the Biomechanical and Biological Response of Stretched Skin

确定拉伸皮肤的生物力学和生物反应

基本信息

批准号：
9222011
负责人：
ARUN K GOSAIN
金额：
$ 15.24万
依托单位：
LURIE CHILDREN'S HOSPITAL OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9222011
关键词：
Adopted American Anatomy Animals Area Biological Biological Markers Biomechanics Burn injury Cells Child Clinical Clinical Protocols Complex Complication Computer Simulation Data Development Ear Engineering Evaluation Event Evolution Excision Family suidae Fibroblasts Foundations Future Gene Activation Gene Expression Gene Expression Profiling Genes Geometry Growth Harvest Head and neck structure Histologic Histology Immunohistochemistry Implant Interdisciplinary Study Lesion Limb structure Location Malignant - descriptor Mammaplasty Measures Mechanics Miniature Swine Modeling Molecular Pathway interactions Plastic Surgeon Procedures Process Property Protocols documentation Public Health Reconstructive Surgical Procedures Recruitment Activity Research Scalp structure Site Skin Skin Tissue Skin wound Societies Stretching Surface Techniques Three-dimensional analysis Time TimeLine Tissue Donors Tissue Engineering Tissue Expanders Tissue Expansion Tissue Model Tissues Universities Variant Wisconsin Wound Healing base computerized experimental study human study improved outcome in vivo Model keratinocyte mechanotransduction member multidisciplinary novel process optimization public health relevance reconstruction response skin lesion subcutaneous transcriptome transcriptome sequencing

项目摘要

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.

描述（由申请人提供）：2013 年，美国整形外科医生协会成员仅用于乳房重建就放置了 68,607 个组织扩张器，虽然组织扩张（拉伸皮肤以促进生长的过程）已成功使用多年，但并发症发生率较高。仍然很高，特别是在可复张正常皮肤最少的区域，如头部、颈部和四肢。扩张的固有问题之一是分子组织事件和皮肤机械变化都会发生响应。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传导途径，但组织响应拉伸的实际机制涉及复杂的相互作用，这些相互作用无法单独在细胞中复制。为了充分阐明这些数据，需要一个能够进行生物力学和生物学评估的体内模型，我们发现皮肤生长变化并且在最大区域达到最大。我们建立的小型猪扩张模型是与斯坦福工程学院和大学合作的多学科努力。威斯康星州密尔沃基市的公司利用计算机 3D 分析来精确计算动物皮肤任意点的拉伸和表面积增长。我们将在四只小型猪的两个部位植入组织扩张器，每个扩张器将在不同时间收获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，这些数据将与拉伸相关联，以阐明生物力学和分子反应的时间表。我们希望这些实验能够确定皮肤对拉伸的生长反应，并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其固有的。变化在受辐射组织的这些途径中，还将提供即时的临床信息，以优化当前的组织扩张技术，特别是在类似供体组织高度有限的区域，例如头部、颈部和四肢。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Improving tissue expansion protocols through computational modeling.

DOI：
10.1016/j.jmbbm.2018.03.034
发表时间：
2018-06
期刊：
Journal of the mechanical behavior of biomedical materials
影响因子：
3.9
作者：
Lee T;Vaca EE;Ledwon JK;Bae H;Topczewska JM;Turin SY;Kuhl E;Gosain AK;Tepole AB
通讯作者：
Tepole AB

Determining the Differential Effects of Stretch and Growth in Tissue-Expanded Skin: Combining Isogeometric Analysis and Continuum Mechanics in a Porcine Model.

DOI：
10.1097/dss.0000000000001228
发表时间：
2018-01
期刊：
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]
影响因子：
0
作者：
Purnell CA;Gart MS;Buganza-Tepole A;Tomaszewski JP;Topczewska JM;Kuhl E;Gosain AK
通讯作者：
Gosain AK

Quantification of Strain in a Porcine Model of Skin Expansion Using Multi-View Stereo and Isogeometric Kinematics.