more promising technique.
The ability to measure the forces generated by the BEHM as it contracts is crucial, Birla explains. It's made possible by a precise instrument called an optical force transducer that gives more precise readings than that used by other teams.
The measurement showed that the BEHM that had formed in just four days after a million cells were layered on fibrin gel could contract with an active force of more than 800 micro-Newtons. That's still only about half the force generated within the tissue of an actual beating heart, but it's much higher than the forces created by engineered heart tissue samples grown and reported by other researchers. Birla says the team expects to see greater forces created by BEHM in future experiments that will bathe the cells in an environment that's even more similar to the body's internal conditions.
In the new paper, the team reports that contraction forces increased when the BEHM tissues were bathed in a solution that included additional calcium and a drug that acts on beta-adrenergic receptors. Both are important to the signaling required to produce cohesive action by cells in tissue.
The U-M team also assessed the BEHM's structure and function at different stages in its development. First author and postdoctoral fellow Yen-Chih Huang, Ph.D., of the U-M Division of Biomedical Engineering, led the creation of the modeling system. Co-author and research associate Luda Khait examined the tissue using special stains that revealed the presence and concentration of the fibrin gel, and of collagen generated by the cells as they organized into tissue.
Over the course of several days, the fibrin broke down as intended, after fulfilling its role as a temporary support for the cells. This may be a key achievement for future use of BEHM as a treatment option, because the tissue could be grown and implanted relatively quickly.
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