3-D Imaging Reveals Regenerated Tissue to Improve Growth

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Bone regeneration soon will play a key role in oral health as dentists and engineers build tiny scaffolds inside the mouth to facilitate the growth of new cells. Yet clinicians need to be able to see how this growth is progressing on the microscopic level. Yu Chen, PhD, of the University of Maryland is now developing a system that provides noninvasive, 3-D imaging of this engineered tissue.

“Three-dimensional cell-based tissue grafts have been increasingly useful in tissue engineering and regenerative medicine,” said Chen, an associate professor with the Fischell Department of Bioengineering and the recipient of a 4-year, $1.20 million National Institutes of Health Research Project Grant to develop the imaging system.

“A critical building block in tissue engineering is the scaffold, which can act as the supporting medium to deliver cell populations and induce ingrowth of vessels and surrounding tissues,” he explained. “Therefore, it is necessary to develop tools to characterize the architecture of the scaffold.”

Such scaffolds deliver progenitor cell populations or support structures for surrounding tissue ingrowth. Their composition, porosity, pore size, and pore interconnectivity can determine the success of the engineered tissue. These scaffolds, then, need to mimic the surrounding tissue morphology, structure, and function and improve mechanical stability between the engineered tissue and surrounding native bone.  

Researchers don’t have any nondestructive methods for analyzing engineered tissue structures and stem cell functions beyond traditional microscopy, though. As a result, they had limited ability to characterize cells located deep inside scaffolds. Today’s techniques involve complex preparation and risk damaging the scaffold. They also can be long and expensive.

Instead, Chen’s platform uses optical coherence tomography and fluorescence laminar optical tomography to characterize cell-scaffold interaction. A noninvasive technique, optical coherence tomography uses light to capture micrometer-resolution, 3-D images of biological tissue. Fluorescence laminar optical tomography uses fluorescent light to produce high-resolution tissue images.

By visualizing the scaffold’s internal structure in 3-D, optical coherence tomography enables subsequent image processing to quantitatively investigate pore size, porosity, interconnectivity, and other characteristics. Fluorescence laminar optical tomography visualizes cell viability, proliferation, distribution, and differentiation within the scaffold over time and space.

With Chen’s system, researchers will be able to evaluate structural and cellular information simultaneously to study cell-scaffold interaction and collect feedback on scaffold design to optimize cellular function. It could have a significant impact on how engineers construct and evaluate tissue scaffolds and enable major advances in bone tissue engineering.

Chen is working with John Fisher, a bioengineering professor and associate chair, and John Caccamese Jr, associate professor of oral-maxillofacial surgery at the University of Maryland Medical System and School of Dentistry. Their work is supported by the Mpowering the State research initiative, which facilitates collaboration among the university’s campuses.

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