Noninvasive imaging and characterization of engineered tissues would greatly enable the development, testing, and commercialization of new therapies. Ultrasound imaging and microscopy have been used to characterize some aspects of tissue structure, but conventional ultrasound techniques are hampered by instrument-dependence and are limited to qualitative assessment of morphology. The objective of this two-year exploratory project is to develop a quantitative imaging technique for the rapid and high resolution characterization of the composition, structure and mechanical properties of mineralized engineered tissues. It applies high frequency spectral ultrasound imaging (SUSI) to create high resolution images and power spectra of mineral-containing tissues. Parametric analysis of the power spectra provides information on the location, density, and particle size of the mineral component. Augmentation of SUSI with acoustic radiation force (ARF) elastography allows measurement of the local and bulk mechanical properties. The project has three Specific Aims (SA). In SA1 we will demonstrate the use of SUSI to quantitatively characterize the spatiotemporal development of a mineral phase in three dimensional (3D) engineered orthopaedic tissues. In SA2 we will implement ARF elastography for noncontact measurement of tissue mechanical properties in 3D engineered orthopaedic tissues. Finally, in SA3 we will correlate the composition and structure information from SA1 with the mechanical property data from SA2. Replacing the currently used destructive biochemical and histological methods of tissue characterization with noninvasive, spatiotemporal characterization of tissue development would greatly enhance research in tissue engineering. In addition, such methods would facilitate quality control and monitoring of engineered tissue products. The ability to correlate composition and mechanical properties in developing tissues over time also could lead to new insights into structure-function relationships and mechanobiology.

Public Health Relevance

Current methods to characterize engineered tissues in vitro are destructive and require complex sample processing. In contrast, this project will apply advanced ultrasound imaging techniques to noninvasively and quantitatively characterize the composition and mechanical properties of developing engineered musculoskeletal tissues. Such a method could aid in research and development of new tissue engineering products.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR064041-01A1
Application #
8583800
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Lester, Gayle E
Project Start
2013-09-01
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$198,263
Indirect Cost
$70,763
Name
University of Michigan Ann Arbor
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Gudur, Madhu Sudhan Reddy; Rao, Rameshwar R; Peterson, Alexis W et al. (2014) Noninvasive quantification of in vitro osteoblastic differentiation in 3D engineered tissue constructs using spectral ultrasound imaging. PLoS One 9:e85749