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.

Public Health Relevance

Tissue expansion is an extremely common reconstructive surgical procedure where skin is grown through stretch; this procedure is essential but has high complication rates. Through our research of tissue expansion in pigs, we will determine the temporal evolution and regional variation over a full expanded patch of tissue, as well as the biological mechanisms that contribute to this growth. This research is important to public health because by understanding the processes by which tissue expansion occurs, we will be better prepared to decrease complications associated with this procedure and improve outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EB021590-02
Application #
9222011
Study Section
Special Emphasis Panel (ZRG1-SBIB-Q (80)S)
Program Officer
Hunziker, Rosemarie
Project Start
2016-04-01
Project End
2018-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
2
Fiscal Year
2017
Total Cost
$137,138
Indirect Cost
$21,138
Name
Children's Memorial Hospital (Chicago)
Department
Type
Independent Hospitals
DUNS #
074438755
City
Chicago
State
IL
Country
United States
Zip Code
60611
Purnell, Chad A; Gart, Michael S; Buganza-Tepole, Adrián et al. (2018) Determining the Differential Effects of Stretch and Growth in Tissue-Expanded Skin: Combining Isogeometric Analysis and Continuum Mechanics in a Porcine Model. Dermatol Surg 44:48-52
Turin, Sergey Y; Ledwon, Joanna K; Bae, Hanna et al. (2018) Digital analysis yields more reliable and accurate measures of dermal and epidermal thickness in histologically processed specimens compared to traditional methods. Exp Dermatol 27:687-690
Lee, Taeksang; Vaca, Elbert E; Ledwon, Joanna K et al. (2018) Improving tissue expansion protocols through computational modeling. J Mech Behav Biomed Mater 82:224-234
Buganza Tepole, Adrian; Vaca, Elbert E; Purnell, Chad A et al. (2017) Quantification of Strain in a Porcine Model of Skin Expansion Using Multi-View Stereo and Isogeometric Kinematics. J Vis Exp :