Non-invasively monitoring the extent of tissue scaffold degradation, cellular growth, and tissue development will greatly help tissue engineers to non-destructively evaluate candidate scaffold performance in vivo. Biodegradable polymer scaffolds are used to support cells and growing tissues until they are replaced by the body's own extracellular matrix (ECM). Two main challenges in creating the ideal biodegradable polymer scaffold are: (1) the scaffold must have a defined shape and porous internal architecture suitable for direct tissue ingrowths but with appropriate mechanical and degradation properties and (2) the scaffold must have the right surface properties to provide favorable conditions for cells to attach differentiate and lay down ECM. To design scaffolds which appropriately transfer their mechanical load over time to the in growing tissue, temporal data are required that verify the mechanical viability of the remodeling construct. Current analysis methods are destructive, requiring animal euthanasia and explanting the construct for histological and direct mechanical characterization. In addition, different samples are prepared and measured at varying times, but high growth deviation between specimens makes analysis difficult. Ideally, tissue engineers need a system that can non-invasively monitor growth in the same specimen over time. Other imaging methods, such as magnetic resonance imaging (MRI) and computed tomography (CT), provide internal scaffold structural information, but they are limited to providing only morphological information. Ultrasound easticity imaging (UEI) based on phase-sensitive speckle tracking can characterize the mechanical, structural, and functional change of the implanted engineered tissues at very high resolution and sensitivity. Local UEI offers the potential to radically improve the biomaterial scaffold design and engineered tissue growth techniques. The long term goal of this research program is to develop a novel noninvasive functional imaging modality in the field of tissue engineering and regenerative medicine. The objective of the current project is to evaluate UEI as noninvasive imaging tool to assess mechanical, structural, and functional characteristics of the scaffold degradation and tissue ingrowth.
The specific aims are: (1) Establish the in vitro relationship between noninvasive UEI and the mechanical and structural characteristics of the biomaterial scaffold degradation. (2) Establish the in vivo relationship between noninvasive UEI and the mechanical, structural, and functional characteristics of simultaneous tissue growing and scaffold degradation.
These specific aims will be evaluated using novel polyurethane-based soft tissue scaffolds with three different degradation rates. In-vivo feasibility will also be demonstrated using the rat abdominal repair model. If successful, UEI integrated into a commercial ultrasound scanner can also be rapidly translated into clinical practice since it is based upon novel processing of ultrasound data that can be obtained conveniently and non-invasively from human subjects

Public Health Relevance

Tissue Engineering is an emerging, interdisciplinary field which is full of promise for those in need of organ and tissue replacement and repair. However, some major limitations with the development and translation remained unsolved mainly due to the limitations of laboratory feedback capabilities, especially non-invasive assessment tool for the implants in animal study. Clinical application of tissue engineering treatments will also require the ability to non-invasively monitor functional tissue regeneration. The proposed ultrasound elasticity imaging technique will provide quantitative assessment and monitoring of the mechanical strength of the engineered tissue as it grows into the native tissue. This technique can be easily integrated into a commercial ultrasound scanner for real-time in-vivo animal study, significantly reducing the number of animals required in the study, and eventually as a clinical tool to monitor the tissue engineering treatments.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-SBIB-J (80))
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Hunziker, Rosemarie
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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