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

项目摘要 乳腺癌影响八分之一的女性一生，是女性第二大常见癌症。组织 扩张（TE）是乳房切除术后乳房重建的最常用技术。可惜 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，不包括不良 化妆品和身体形象的负面影响。生长皮肤的形状和数量足以实现 自然的乳房形状是一个关键的需要，因为成功的重建已被证明可以显着改善幸存者的 生活质量TE在具有复杂三维（3D）几何形状的区域中具有挑战性， 拉伸和增长分布目前无法预测。我们率先应用有限的 元素工具，以及一种新的实验方案，在猪，使我们能够测量， 第一次，组织规模的预应变，由膨胀引起的变形，以及在现实TE中导致的生长 协议.猪模型证实了我们的计算模型的预测， 变形是不均匀的，扩张器的顶点经历最大的应变，并且生长 图案反映变形轮廓。在这里，我们将利用我们独特的动物模型， 组织尺度的变形和生长，以及相应的细胞行为和微观结构 在TE期间的特定时间点重塑。这一信息将提供第一个完整的图片慢性 皮肤对不同尺度的机械提示的适应。这些数据将使我们能够改善我们以前的计算能力。 模型，并创建，校准和验证一个新的多尺度模型。具体来说，我们将预测微观 重塑作为响应拉伸的细胞行为的函数（目的1），预测组织生长期间的皮肤生长 使用新的器官规模模型进行扩展（目标2），并将实验和模型转化为临床环境 乳房切除术后的乳房重建，以预测人体皮肤的生长作为充气时间的函数 量（目标3）。因此，该项目将增加皮肤生物学的基础知识，帮助改善临床 并为进一步研究治疗干预提供了主题。

Project Summary 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.