Bone tissue regeneration is necessary to restore skeletal function following a variety of clinical procedures, including bone fracture repair, reconstructive surgery, and spinal fusions. Tissue-engineered bone offers a number of advantages over traditional bone grafts used for the repair and regeneration of bone. However, the current methods employed to evaluate and optimize the growth of engineered bone tissue lack the spatial and temporal resolution to characterize the dynamic cell-matrix interactions that occur during tissue development. The objective of this project is to develop quantitative optical biomarkers to identify and monitor changes in the biochemical, microstructural, and overall mechanical properties of engineered bone tissue during its in vitro development. This work focuses on the dynamic changes that occur as three-dimensional silk scaffolds seeded with human mesenchymal stem cells develop into functional bone tissue. The central hypothesis of this proposal is that endogenous optical signals can be measured non-invasively using multi-photon imaging and depth-resolved light scattering spectroscopy to determine the biochemical and microstructural properties of the developing tissue. To test this hypothesis, the intrinsic fluorescence and light scattering signals from different cellular and extracellular matrix components will be identified in Aim 1 and correlated with traditional histological and molecular biology techniques. The optical biomarkers for microstructural organization identified in Aim 1 will be used to predict the overall mechanical function of the bone tissue in tension and compression in Aim 2. Collectively, these aims will provide a unique understanding of how the biochemical status and mechanical function of engineered tissue changes during osteogenesis. By using only non-invasive techniques that identify intrinsic sources of optical contrast, the outcomes of this proposed research can be used to optimize the future approaches to engineering functional bone tissue and will enable a means to monitor engineered constructs as they are incorporated into native tissue following surgical repair.

Public Health Relevance

The proposed research will provide a set of non-invasive optical techniques to assess bone structure and function, which will improve the efficiency by which tissue engineering techniques are refined to develop functional bone substitutes. For the millions of patients that undergo surgical procedures that involve bone repair, this research will also provide a means to evaluate regeneration with greater resolution than traditional imaging techniques without the use of ionizing radiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR061933-02
Application #
8490507
Study Section
Special Emphasis Panel (ZRG1-F14-A (20))
Program Officer
Wang, Fei
Project Start
2011-08-01
Project End
2013-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$49,214
Indirect Cost
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; Sullivan, Kelly E; Liu, Zhiyi et al. (2016) Optical metrics of the extracellular matrix predict compositional and mechanical changes after myocardial infarction. Sci Rep 6:35823
Quinn, Kyle P; Leal, Ermelindo C; Tellechea, Ana et al. (2016) Diabetic Wounds Exhibit Distinct Microstructural and Metabolic Heterogeneity through Label-Free Multiphoton Microscopy. J Invest Dermatol 136:342-4
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
Özkucur, Nurdan; Quinn, Kyle P; Pang, Jin C et al. (2015) Membrane potential depolarization causes alterations in neuron arrangement and connectivity in cocultures. Brain Behav 5:24-38
Bellas, Evangelia; Rollins, Amanda; Moreau, Jodie E et al. (2015) Equine model for soft-tissue regeneration. J Biomed Mater Res B Appl Biomater 103:1217-27
Xylas, Joanna; Varone, Antonio; Quinn, Kyle P et al. (2015) Noninvasive assessment of mitochondrial organization in three-dimensional tissues reveals changes associated with cancer development. Int J Cancer 136:322-32
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
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
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

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