Heart 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. Now, Tel Aviv University researchers may have a solution for a new gold standard in cardiac tissue engineering.

Dr. Tal Dvir and his graduate student Michal Shevach of TAU’s Department of Biotechnology, Department of Materials Science and Engineering, and Center for Nanoscience and Nanotechnology, have been developing sophisticated micro- and nano-technological tools – ranging in size from 1µm to 0.001µm – to develop functional substitutes for damaged heart tissue. Searching for innovative methods to restore heart function, especially transplantable cardiac patches to replace damaged heart tissue, Dvir struck gold. He and his team discovered that gold particles are able to increase the conductivity of biomaterials.

Their model for a superior hybrid cardiac patch incorporates biomaterial harvested from patients and gold nanoparticles.

“Our goal was twofold,” Dvir says. “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.”

A scaffold for heart cells

Researchers engineer cardiac tissue 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. Through 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 improve heart function.

According to Dvir, recent scientific efforts are focusing on the use of scaffolds from pig hearts to supply the collagen grid – the extracellular matrix – with the goal of implanting them in human patients. However, residual remnants of antigens, such as sugar or other molecules, can cause the human patients’ immune cells to attack the animal matrix.

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

Using gold to create a cardiac network

The second dilemma, establishing functional network signals, was complicated by using the human extracellular matrix.

“Engineered patches do not establish connections immediately,” Dvir says. “Biomaterial harvested for a matrix tends to be insulating and thus disruptive to network signals.”

Dvir also explored the integration of gold nanoparticles into cardiac tissue.

“To address our electrical signaling problem, we deposited gold nanoparticles on the surface of our patient-harvested matrix, ‘decorating’ the biomaterial with conductors,” Dvir states. “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 minimal immune response,” Dvir explains. “Then we plan to move it to large animals and after that, to clinical trials.”

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