Aug. 6, 2002 CHAPEL HILL - The collaboration between cardiologist and orthopedist may at first seem novel, if not odd. But just such an interdisciplinary connection at the University of North Carolina at Chapel Hill has yielded potentially useful fruit: a bioengineered, rhythmically beating experimental model of heart muscle.
The new model system is a bioartificial trabeculum, or BAT. Trabecula are thin sections of cardiac tissue within the inner surface of the heart's main pumping chambers. Although still some distance away from any human clinical application, the model could prove a valuable scientific tool for exploring cardiac disease, including electrical and mechanical disturbances of the heart.
Details of the heart tissue model are being presented Monday (Aug. 5) to the World Congress of Biomechanics in Calgary, Canada.
"The purpose of our study was to explore the possibility that one could take isolated heart cells and under proper conditions allow them to coalesce and attach to each other in a functional way, thereby creating an artificial tissue," said cardiologist and co-developer Dr. Wayne E. Cascio, associate professor of medicine at UNC.
Cascio said the idea for the BAT originated with a biomedical engineering lecture by Dr. Albert J. Banes, UNC professor of orthopedics. Banes had spoken about his work on the development artificial tendons. Through a company he founded 18 years ago, Flexcell International in Hillsborough, N.C., Banes had developed a special tissue plate that has proven a useful framework in which cells in a liquid collagen gel could remodel on their own to form a more tissue-like structure. Other work elsewhere has involved rigid structures or lattices upon which cells attach to and grow.
"The fundamental basis for that company was a flexible bottom culture plate with the thought that all cells in tissues in our body are subjected to some forms of mechanical load, cyclic tension being one of them," Banes said. "We thought it would be better to grow cells in a dynamic environment, on a flexible substrate. We could then stretch the tissue cells in a certain way to simulate the effects of mechanical loads on tendon, muscle bone, ligament, and cartilage and also add the shear stress that occurs during fluid flow in blood vessels. Dr. Cascio very astutely thought we could grow cardiac myocytes and make a cardiac muscle tissue-like material to test in culture. And that's where the collaboration began." In developing the tissue model, Cascio and his laboratory assistant Joseph Brackhan, isolated cardiac myocytes from one-day-old rats.
These were mixed in a solution of collagen and serum and allowed to gel under incubation in a Flexcell Tissue Train Plate. (See link to illustration at bottom of release.) The tissue train plates have two nylon tethers at opposite ends of each well and a flexible silicon rubber bottom. After four days in culture, the heart cells migrated toward the center of the gel to form a dense cord of tissue that extended between the two tethers.
The tissue strand rhythmically contracts at 100 beats per minute, easily observed with a low-power microscope. Tests reveal striations characteristic of cardiac tissue and cell-to-cell coupling also characteristic of cardiac tissue.
The team's long-term goals are to apply this system to study the effects of mechanical loading on normal cardiac physiology and to develop a model system for the study of cardiac illnesses such as congestive heart failure.
"In my lab, we're specifically interested in generating cardiac myocytes with certain electrical or contractile properties by manipulating the genetics of the cells and then re-forming them into functional tissue to assess their properties," Cascio said. He added that some researchers might view this model as a means to generate tissue patches that might be applied to the surface of the heart or to incorporate into a diseased heart - cardiomyoplasty, a kind of cardiac plastic surgery. "But this would be a very early stage of such an approach," he said.
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