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Cardiac ‘Patch’ Could Replace Transplants, Researchers Say

Gold nanoparticles take center stage in tissue repair

Because heart cells cannot multiply and cardiac muscles contain few stem cells, heart tissue is unable to repair itself after a heart attack. According to a study published in Nano Letters, researchers at Tel Aviv University in Israel have met this challenge by literally setting a new “gold standard” in cardiac tissue engineering.

Dr. Tal Dvir and a graduate student, Michal Shevach, have been developing sophisticated micro- and nanotechnology tools — ranging in size from one millionth to one billionth of a meter — to create functional substitutes for damaged heart tissues. Searching for new methods to restore heart function, especially cardiac “patches” that could be transplanted into the body to replace damaged heart tissue, Dvir and his team discovered that gold particles are able to increase the conductivity of biomaterials.

“Our goal was twofold: to engineer tissue that would not trigger an immune response in the patient, and to fabricate a functional patch not beset by signaling or conductivity problems,” Dvir said.

Cardiac tissue is engineered by allowing cells taken from the patient or other sources to grow on a three-dimensional scaffold, similar to the collagen grid that naturally supports the cells in the heart. Over time, the cells come together to form a tissue that generates its own electrical impulses and expands and contracts spontaneously. The tissue can then be surgically implanted as a patch to replace damaged tissue and to improve heart function in patients.

According to Dvir, recent efforts have focused on the use of scaffolds from pig hearts to supply the collagen grid, or extracellular matrix, with the goal of implanting these scaffolds in human patients. However, because of residual remnants of antigens, such as sugar or other molecules, the patient’s immune cells are likely to attack the animal matrix.

To address this immunogenic response, Dvir and his colleagues suggested a new approach. Fatty tissue from the patient’s own stomach could be easily harvested, its cells efficiently removed, and the remaining matrix preserved. This scaffold does not provoke an immune response, according to Dvir.

The second dilemma — to establish functional network signals — was complicated by the use of the human extracellular matrix. “Engineered patches do not establish connections immediately,” Dvir explained. “Biomaterial harvested for a matrix tends to be insulating and thus disruptive to network signals.”

At his laboratory, Dvir explored the integration of gold nanoparticles into cardiac tissue to optimize electrical signaling between cells. “To address our electrical signaling problem, we deposited gold nanoparticles on the surface of our patient-harvested matrix, ‘decorating’ the biomaterial with conductors,” Dvir said. “The result was that the nonimmunogenic hybrid patch contracted nicely due to the nanoparticles, transferring electrical signals much faster and more efficiently than non-modified scaffolds.”

Preliminary test results of the hybrid patch in animals have been positive. “We now have to prove that these autologous hybrid cardiac patches improve heart function after heart attacks with a minimal immune response,” Dvir said. “Then we plan to move it to large animals and, after that, to clinical trials.”

Source: Tel Aviv University; September 30, 2014.

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