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

• 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
• 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

 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.

 DESCRIPTION (provided by applicable): 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 inherit 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 mechanism transduction 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.此外，尚未确定皮肤生长的比率。为了完全阐明这些数据，需要一个允许生物力学和生物学评估的体内模型。 We hypothesize that skin growth varies and is maximum in areas of maximum stretch, and this will be correlated with gene expression and activation of known mechanotransduction pathways.我们既定的小型组织扩展模型是与斯坦福工程和大学的合作，多学科的努力 威斯康星州 - 密尔沃基（Milwaukee）利用计算机化的3D分析，以精确计算动物皮肤任何点的拉伸和表面积的生长。我们将在四个Minipigs中的两个地点植入组织扩张器，每个扩展器将在不同的时间填充。这种拉伸皮肤的收获将促进组织生长计算，以及井组织学，免疫组织化学和基因表达分析。这些数据将相关以伸展以阐明生物力学和分子对变形力的响应的时间表。我们预计这些实验将使我们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表。这些数据将用于进一步研究来确定继承变化 在这些途径中的这些途径中，还将提供即时的临床信息，以优化组织扩张中的当前技术，尤其是在供体组织等高度有限的地区，例如头部，颈部和四肢。

项目成果

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.]
• 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.

• DOI: 10.3791/55052
• 发表时间: 2017-04-16
• 期刊: Journal of visualized experiments : JoVE
• 作者: Buganza Tepole A;Vaca EE;Purnell CA;Gart M;McGrath J;Kuhl E;Gosain AK
• 通讯作者: Gosain AK