Tissue engineering and regenerative medicine (TE/RM) is an evolving interdisciplinary field that integrates engineering with biology and medicine for the development of functional tissues and organs. Monitoring of tissues in vitro prior to implantation and assessment of tissues in vivo during development are both essential in order to optimize the regeneration of tissue and the restoration of organ function. Since direct visualization of developing tissues, i.e., tissue sampling via sacrifice or biopsy, is invasive and wasteful, one challenge in TE/RM is establishing non-invasive tools to monitor the development of the constructs in vitro and in vivo. In addition, visualization of the transitional region between the tissue implant and the surrounding tissues is critical to the establishment of the overall success of the procedure. MRI is increasingly being used in TE/RM to monitor the remodeling and regeneration of engineered tissues. Bioengineers can now generate spatial maps of MR relaxation times, diffusion coefficients, magnetization transfer ratios, and the shear modulus to monitor, for example, new bone growth for prosthetic therapy in TE/RM. We hypothesize that MR can be extended to monitor quantitatively the growth of engineered tissues including bone, fat, and cartilage. By its periodic application in vitro and in vivo MR can enable the much anticipated successes in TE/RM. Our preliminary data demonstrate that quantitative MR methods can be applied to characterize non-invasively the changes associated with adipogenesis, osteogenesis, and chondrogenesis in tissue-engineered MSC-based constructs. This in vitro work established that MR acquired data can be directly correlated with the underlying tissue composition and structure as measured by biochemical and histological techniques. Our long term goal is to extend these methods to assess the structure and function of developing, engineered tissues in vivo. In order to achieve this goal we have assembled an interdisciplinary team of imaging scientists, tissue engineers and clinicians. The proposed work forms a 5-year plan to establish useful clinical MR tools for the optimization of TE/RM specifically for chondrogenic tissues. Public Health Relevance Statement (provided by applicant): The objective of this study is to develop new techniques for monitoring engineered chondrogenic tissues using magnetic resonance imaging and magnetic resonance elastography. Magnetic resonance imaging provides three dimensional views of developing tissue at all stages of growth without the need to sacrifice the animal or to biopsy the tissue. Magnetic resonance elastography gives a direct measure of the strength and stiffness of regenerating tissue: critical information needed to guide the design of new methods of tissue engineering and to assess the success of tissue implants for restoring tissue damaged by disease, injury or cancer treatment.

Public Health Relevance

The objective of this study is to develop new techniques for monitoring engineered chondrogenic tissues using magnetic resonance imaging and magnetic resonance elastography. Magnetic resonance imaging provides three dimensional views of developing tissue at all stages of growth without the need to sacrifice the animal or to biopsy the tissue. Magnetic resonance elastography gives a direct measure of the strength and stiffness of regenerating tissue: critical information needed to guide the design of new methods of tissue engineering and to assess the success of tissue implants for restoring tissue damaged by disease, injury or cancer treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB007537-04
Application #
8232120
Study Section
Special Emphasis Panel (ZEB1-OSR-D (J1))
Program Officer
Hunziker, Rosemarie
Project Start
2009-05-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
4
Fiscal Year
2012
Total Cost
$353,260
Indirect Cost
$77,521
Name
University of Illinois at Chicago
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Klatt, Dieter; Johnson, Curtis L; Magin, Richard L (2015) Simultaneous, multidirectional acquisition of displacement fields in magnetic resonance elastography of the in vivo human brain. J Magn Reson Imaging 42:297-304
Magin, Richard L; Ingo, Carson; Triplett, William et al. (2014) Classification of fractional order biomarkers for anomalous diffusion using q-space entropy. Crit Rev Biomed Eng 42:63-83
Yin, Ziying; Magin, Richard L; Klatt, Dieter (2014) Simultaneous MR elastography and diffusion acquisitions: diffusion-MRE (dMRE). Magn Reson Med 71:1682-8
Yin, Ziying; Schmid, Thomas M; Yasar, Temel K et al. (2014) Mechanical characterization of tissue-engineered cartilage using microscopic magnetic resonance elastography. Tissue Eng Part C Methods 20:611-9
Kotecha, Mrignayani; Klatt, Dieter; Magin, Richard L (2013) Monitoring cartilage tissue engineering using magnetic resonance spectroscopy, imaging, and elastography. Tissue Eng Part B Rev 19:470-84
Klatt, Dieter; Yasar, Temel K; Royston, Thomas J et al. (2013) Sample interval modulation for the simultaneous acquisition of displacement vector data in magnetic resonance elastography: theory and application. Phys Med Biol 58:8663-75
Magin, Richard L; Ingo, Carson; Colon-Perez, Luis et al. (2013) Characterization of Anomalous Diffusion in Porous Biological Tissues Using Fractional Order Derivatives and Entropy. Microporous Mesoporous Mater 178:39-43
Yasar, Temel K; Klatt, Dieter; Magin, Richard L et al. (2013) Selective spectral displacement projection for multifrequency MRE. Phys Med Biol 58:5771-81
Kotecha, Mrignayani; Ravindran, Sriram; Schmid, Thomas M et al. (2013) Application of sodium triple-quantum coherence NMR spectroscopy for the study of growth dynamics in cartilage tissue engineering. NMR Biomed 26:709-17
Ravindran, Sriram; Gao, Qi; Kotecha, Mrignayani et al. (2012) Biomimetic extracellular matrix-incorporated scaffold induces osteogenic gene expression in human marrow stromal cells. Tissue Eng Part A 18:295-309

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