Multi-Scale Modeling to Predict Long-Term Growth and Remodeling of Skin in Response to Stretch

家长资助：多尺度建模预测皮肤的长期生长和重塑 拉伸（1 R 01 AR 074525 - 01 A1） 翻译后摘要：乳腺癌影响1在8妇女在其一生中，是第二个最常见的癌症， 妇女组织扩张术（TE）是乳房切除术后乳房再造最常用的技术。 不幸的是，在大型系列中，TE乳房重建的并发症发生率可能为15%或更高， 不包括不美观和对身体形象的负面影响。在形状和数量上生长皮肤 充分实现自然乳房形状是关键需求，因为成功的重建已被证明， 明显改善幸存者？生活质量TE在具有复杂三维（3D） 几何形状，显示目前无法预期的不平等拉伸和生长分布。我们有 开创了有限元工具在TE中的应用，以及在猪中的新实验方案 这使我们能够第一次测量组织规模的预应变，由扩张引起的变形， 并导致现实TE协议的增长。猪模型证实了我们的预测 计算模型，变形是不均匀的，与顶点的膨胀经历 最大的应变，生长模式反映了变形轮廓。在这里，我们将利用我们独特的 动物模型，以准确地测量组织尺度的变形和生长，连同相应的 TE期间特定时间点的细胞行为和微结构重塑。这些信息将提供 第一个完整的图片慢性皮肤适应机械线索跨尺度。这些数据可以让我们 改进我们以前的计算模型，并创建、校准和验证新的多尺度模型。 具体来说，我们将预测微观重塑作为细胞行为的函数，以响应拉伸（目的 1），使用新的器官尺度模型预测组织扩张期间的皮肤生长（目标2），并将 实验和模型的临床设置乳房切除术后乳房再造，以预测生长 人体皮肤作为充气时间和体积的函数（目标3）。因此，该项目将增加基本的 皮肤生物学知识，有助于改善临床结果，并为进一步研究提供主题， 治疗干预

Parent grant: Multi-Scale Modeling to Predict Long-Term Growth and Remodeling of Skin in Response to Stretch (1R01AR074525-01A1) Abstract: Breast cancer affects 1 in 8 women over their lifetime, and is the second most common cancer in women. Tissue expansion (TE) is the most common technique for breast reconstruction after mastectomy. Unfortunately, the rate of complications with TE for breast reconstruction can be 15% or higher in large series, not including poor cosmetic and the negative impact to body image. Growing skin in shape and amount adequate to achieve a natural breast shape is a key need, as successful reconstruction has been shown to markedly improve survivors? quality of life. TE is challenging in areas with complex three-dimensional (3D) geometries, which show unequal stretch and growth distributions that cannot be currently anticipated. We have pioneered the application of finite element tools to TE, as well as a novel experimental protocol in the swine that has allowed us to measure, for the first time, tissue scale prestrain, deformation induced by expansion, and resulting growth in realistic TE protocols. The porcine model has confirmed predictions made with our computational model, that the deformation is heterogeneous, with the apex of the expander undergoing the largest strains, and that the growth patterns reflect the deformation contours. Here we will leverage our unique animal model to measure accurately the tissue scale deformation and growth, together with the corresponding cell behavior and microstructure remodeling at specific time points during TE. This information will provide the first complete picture of chronic skin adaptation to mechanical cues across scales. The data will allow us to improve our previous computational model, and create, calibrate and validate a new multi-scale model. Specifically, we will predict microscopic remodeling as a function of cell behavior in response to stretch (Aim 1), predict skin growth during tissue expansion using a new organ-scale model (Aim 2), and translate the experiment and model to the clinical setting of breast reconstruction after mastectomy to predict the growth of human skin as a function of inflation timing and volume (Aim 3). This project will thus add to the fundamental knowledge of skin biology, help improve clinical outcomes and provide topics for further research into therapeutic intervention.