Our long-term goal is to develop non-invasive, optical technologies to monitor the functional development of engineered tissues in vitro and in vivo. The objective of this application is to develop optical biomarkers based on endogenous sources of optical contrast that obviate the use of exogenous stains and can be used to report quantitatively on the biochemical and structural composition of engineered tissues. The proposed studies focus on the characterization of adipose and bone engineered tissues developed from silk scaffolds seeded with human mesenchymal stem cells. The central hypothesis of the application is that linear and non-linear depth- resolved imaging methods based on the natural light scattering and fluorescence signatures of cell and matrix components of engineered tissues can be developed to report on the dynamic changes that occur prior to and following implantation of engineered tissues. Our hypothesis is based on preliminary evidence acquired from in vitro samples, which indicate that endogenous optical signals can be used to monitor changes in the biochemistry and morphology of differentiating stem cells, silk scaffolds and deposited collagen. The rationale for the proposed research is that the establishment of non-invasive methods that allow monitoring of the dynamic changes that occur within engineered tissues will play an essential role in the development and optimization of innovative, functional engineered tissue constructs. To achieve our goal we will characterize the endogenous fluorescence and light scattering signals from different cell and matrix components of engineered tissues developed in vitro (Aim 1). We will develop a system that will optimize acquisition of these optical signals from animals (Aim 2) and we will use these biomarkers to characterize non-invasively the integration of these engineered tissues in vivo following implantation either within a mammary fat pad or a cavarial bone defect mouse model (Aim 3). This will be the first time that dynamic monitoring of the biochemical and structural function of implanted engineered tissues is achieved in vivo using non-invasive means based on endogenous optical signals. This proposal is highly relevant to the improvement of public health as it will enable the efficient development of functional bone and adipose engineered tissues. Thus, millions of patients that undergo surgical procedures for the repair or reconstruction of such tissues will ultimately benefit from this work. Project Narrative This proposal is highly relevant to the improvement of public health as it will enable the efficient development of functional bone and adipose engineered tissues. Thus, millions of patients that undergo surgical procedures for the repair or reconstruction of such tissues will ultimately benefit from this work.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB007542-04
Application #
8286938
Study Section
Special Emphasis Panel (ZEB1-OSR-D (O1))
Program Officer
Hunziker, Rosemarie
Project Start
2009-05-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
4
Fiscal Year
2012
Total Cost
$322,564
Indirect Cost
$108,457
Name
Tufts University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
073134835
City
Medford
State
MA
Country
United States
Zip Code
02155
Quinn, Kyle P; Golberg, Alexander; Broelsch, G Felix et al. (2015) An automated image processing method to quantify collagen fibre organization within cutaneous scar tissue. Exp Dermatol 24:78-80
Varone, Antonio; Xylas, Joanna; Quinn, Kyle P et al. (2014) Endogenous two-photon fluorescence imaging elucidates metabolic changes related to enhanced glycolysis and glutamine consumption in precancerous epithelial tissues. Cancer Res 74:3067-75
Hayden, Rebecca S; Quinn, Kyle P; Alonzo, Carlo A et al. (2014) Quantitative characterization of mineralized silk film remodeling during long-term osteoblast-osteoclast co-culture. Biomaterials 35:3794-802
Williams, C; Quinn, K P; Georgakoudi, I et al. (2014) Young developmental age cardiac extracellular matrix promotes the expansion of neonatal cardiomyocytes in vitro. Acta Biomater 10:194-204
Marturano, Joseph E; Xylas, Joanna F; Sridharan, Gautham V et al. (2014) Lysyl oxidase-mediated collagen crosslinks may be assessed as markers of functional properties of tendon tissue formation. Acta Biomater 10:1370-9
Barnes, Clifford; Speroni, Lucia; Quinn, Kyle P et al. (2014) From single cells to tissues: interactions between the matrix and human breast cells in real time. PLoS One 9:e93325
Speroni, Lucia; Whitt, Gregory S; Xylas, Joanna et al. (2014) Hormonal regulation of epithelial organization in a three-dimensional breast tissue culture model. Tissue Eng Part C Methods 20:42-51
Marturano, Joseph E; Arena, Jeffrey D; Schiller, Zachary A et al. (2013) Characterization of mechanical and biochemical properties of developing embryonic tendon. Proc Natl Acad Sci U S A 110:6370-5
Chang, Tyler; Zimmerley, Maxwell S; Quinn, Kyle P et al. (2013) Non-invasive monitoring of cell metabolism and lipid production in 3D engineered human adipose tissues using label-free multiphoton microscopy. Biomaterials 34:8607-16
MacDonald, Douglas H; Hunter, Martin; Quinn, Kyle P et al. (2013) Autocorrelation method for fractal analysis in nonrectangular image domains. Opt Lett 38:4477-9

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