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Biohybrid hydrogel graft reduces arrhythmia in damaged heart tissue

By Frieda Wiley October 25, 2018
Image of biohybrid hydrogel. Credit: Kaveh Roshanbinfar

The improved functionality of heart muscle spawned by the union of materials science and stem cell biology (a type of bioengineering in which naïve cells can be groomed into new cells that regenerate damaged tissue) has been previously documented in the literature. Using engineered cardiac tissue to treat heart failure is one application of this science. However, existing treatments using bioengineered cardiac tissue frequently cause cardiac arrhythmias, or heartbeat irregularities, and insufficient electrical conduction within cardiac tissue. A research group has now crafted a biomaterial for heart tissue that provides sufficient electrical conduction without compromising heartbeat maturation or causing arrhythmias. The results are reported in a recent issue of Advanced Functional Materials.

“As our system shows, synchronous beating of the constructs with beating rates similar to native cardiac tissue can be potentially used as a regenerative graft for the treatment of myocardial diseases including heart attack,” says Kaveh Roshanbinfar, a doctoral student at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), the primary author of the study.

Roshanbinfar and his colleagues from FAU and other institutions in Germany have developed an engineered hybrid graft for this purpose. The engineered hybrid graft can also support pharmaceutical research by providing a platform to study the pharmacological effects of different drugs on cardiac function while reducing the need for animal studies and expediting the preliminary screening processes in drug development.

Much like engineered tissue, conventional treatments for heart disease including prescription beta blockers and valve replacements often run the risk of causing heart arrhythmias. Similarly, arrhythmias frequently occur in human embryonic stem cell-derived cardiomyocytes, or cells that make up heart tissue, as a consequence of the spontaneous contractions that frequently occur in these cells due to their immature state.

Grafts engineered using conventional methods often produce tissue so densely packed that they create physical hindrance and nonuniform conductivity limiting the ability of cardiomyocytes to efficiently communicate with each other. To reduce the potential for arrhythmias induced by immature cells, researchers usually use external mechanical or electrical stimulation to encourage cellular maturation.

Roshanbinfar and colleagues developed a conductive biohybrid hydrogel system that facilitates electrical communication between cardiomyocytes in a uniform manner without encouraging arrhythmic activity. Composed of collagen, alginate, and electroconductive poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), the hydrogel possesses physical properties that mimic the fibrous features of extracellular matrices while improving electrical coupling and encouraging cardiomyocyte maturation. Previous studies have shown that primary and mouse-derived cardiomyocytes attach well to PEDOT:PSS hydrogels, also increasing its suitability in the engineering of a biohybrid material.

The number of charged functional groups found within/on the surface of hydrogels greatly dictates the hydrogel’s degree of conductivity, but the miscibility of electroconductive polymers and their contractility make them very attractive for tissue engineering, bioactuation, and drug development research.

The researchers selected PEDOT:PSS over the more widely studied polyaniline (PANi) and polypyrrole (PPy) because the latter polymers disperse poorly in water despite their attractive conductivity-supporting features. Moreover, conventional engineering methods such as seeding prefabricated scaffolds and three-dimensional biofabrication yield cell densities that lack homogeneity and uniform conductivity—physical features associated with complications such as physical hindrance and cell death induced by shear stress among other challenges.

“The novelty of our approach is the incorporation of an electroconductive polymer, which facilitates intercellular electrical coupling as well as maturation of stem cell-derived cardiomyocytes without any external stimulations and, therefore, improve the functionality of the final engineered cardiac tissue,” says Felix Engel, professor at FAU and corresponding author. Possible future treatment may involve attaching the hydrogel to the damaged region and letting it then integrate with the surrounding healthy native tissue.

While the study may give doctors a new option in treating heart failure one day, Engel says that future research warrants evaluating the biohybrid hydrogel’s activity through in vivo studies using various drugs that alter cardiac function.

Read the abstract in Advanced Functional Materials.