The most important medical challenges include cardiovascular diseases, stroke, degenerative neurological diseases, diabetes, arthritis, osteoporosis, kidney and liver failure, spinal cord injury, burns, battlefield trauma, and other devastating conditions. Organ transplantation addresses some of these needs, but the scarcity of donors and the risk of immune suppression pose major limitations on transplantation. Regenerative medicine seeks to devise new ways to repair or replace damaged tissues and organs for millions of patients who cannot receive transplants. A core technology is the bioengineering of a functional tissue or organ by seeding living cells onto a biodegradable scaffold and then surgically implanting the construct into a patient. Tissue engineering involves extensive remodeling of cells and scaffolds. A major barrier to progress has been the inability to monitor this dynamic complex biological process in real-time, which makes control and optimization extremely difficult. On the other hand, as defined in the NIH roadmap molecular imaging plays an increasingly important role in the advancement of medicine. The optical molecular imaging tools has now allowed much better understanding of biological interactions at molecular and cellular levels in mouse models of almost all human diseases, and found several major clinical applications. Therefore, we are motivated to integrate these two forefront technologies in biomedical research - tissue engineering and optical molecular imaging - in a single unified framework, and drive a paradigm shift from static assays of cellular function in biopsied tissue or 2D culture models towards systematic analysis of 3D systems. The overall goal of this project is to develop a first-of-its-kind multi-probe multi-modal optical molecular tomography system for regenerative medicine and to demonstrate its utility in assessing the bioengineered blood vessels at the pre- and post-implantation stages. Fluorescent probes will be used to label the tubular scaffold and the two main cell types of blood vessels (endothelial cells lining the lumen, and smooth muscle cells in the wall). Optical fibers embedded within the scaffold will deliver laser light for optical coherence tomography and to excite the fluorescent probes. Innovative algorithms will be developed to reconstruct 3D distributions of multiple fluorescent probes. The proposed imaging system will first be used to track the development of bioengineered vessels in 100?m resolution in a bioreactor mimicking blood flow conditions. Additional fluorescent probes will be used to monitor cell-specific gene expression and verify physiological responses of cells within the engineered vessel. The vessels will then be implanted as interposition grafts in the carotid arteries of living sheep, and will be imaged in 500?m resolution to follow the tissue regeneration and function. Successful completion of the project will create new optical molecular imaging tools with a demonstrated application in vessel engineering, and have major and lasting impacts on many other areas in regenerative medicine.

Public Health Relevance

Regenerative medicine creates an organ or tissue by seeding one's own cells onto a biodegradable scaffold and surgically implants it into him/her. Using bioengineered blood vessels as the first example, this project will develop a sophisticated optical imaging system to observe, analyze and optimize the complex processes of tissue regeneration in the laboratory and in live animals. The results will potentially benefit tens of millions of patients suffering from severely damaged vascular or nervous systems, heart, kidneys, liver, skeleton, bladder, or other organs.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Biomaterials and Biointerfaces Study Section (BMBI)
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Danthi, Narasimhan
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Virginia Polytechnic Institute and State University
Engineering (All Types)
Schools of Engineering
United States
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Niu, Guoguang; Sapoznik, Etai; Lu, Peng et al. (2016) Fluorescent imaging of endothelial cells in bioengineered blood vessels: the impact of crosslinking of the scaffold. J Tissue Eng Regen Med 10:955-966
Xi, Yan; Zhao, Jun; Bennett, James R et al. (2016) Simultaneous CT-MRI Reconstruction for Constrained Imaging Geometries Using Structural Coupling and Compressive Sensing. IEEE Trans Biomed Eng 63:1301-1309
Gurjarpadhye, Abhijit Achyut; DeWitt, Matthew R; Xu, Yong et al. (2015) Dynamic Assessment of the Endothelialization of Tissue-Engineered Blood Vessels Using an Optical Coherence Tomography Catheter-Based Fluorescence Imaging System. Tissue Eng Part C Methods 21:758-66
Idelson, Christopher R; Vogt, William C; King-Casas, Brooks et al. (2015) Effect of mechanical optical clearing on near-infrared spectroscopy. Lasers Surg Med 47:495-502
Cong, Wenxiang; Pan, Zhengwei; Filkins, Robert et al. (2014) X-ray micromodulated luminescence tomography in dual-cone geometry. J Biomed Opt 19:76002
Whited, Bryce M; Rylander, Marissa Nichole (2014) The influence of electrospun scaffold topography on endothelial cell morphology, alignment, and adhesion in response to fluid flow. Biotechnol Bioeng 111:184-95
Cong, Wenxiang; Wang, Chao; Wang, Ge (2014) Stored luminescence computed tomography. Appl Opt 53:5672-6
Cong, Wenxiang; Liu, Fenglin; Wang, Chao et al. (2014) X-ray micro-modulated luminescence tomography (XMLT). Opt Express 22:5572-80
Lu, Peng; Shipton, Matthew; Wang, Anbo et al. (2014) Adaptive control of waveguide modes in a two-mode-fiber. Opt Express 22:2955-64
Wang, Ge; Yu, Hengyong (2013) The meaning of interior tomography. Phys Med Biol 58:R161-86

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