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.

Public Health Relevance

This project seeks to understand and predict the adaptation of skin to stretch across scales. It is based on an experimental model of tissue expansion in the swine, and its translation to the clinical application of breast reconstruction after mastectomy. This work will investigate how skin adapts to mechanical cues in vivo over long time periods by measuring both tissue and cell scale changes and use this information to create a predictive computational model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR074525-02
Application #
9977920
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Tseng, Hung H
Project Start
2019-07-15
Project End
2024-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Purdue University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907