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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 3 - SmartCardiacPatch (Next-Generation Cardiac Tissue Engineering: Smart Self-Regulating Patches)

Teaser

Summary

Ischemic heart disease (IHD) is the most common cause of death in the Western world, accounting for more than 1.8 million deaths each year in Europe, with an annual costs in excess of â‚¬ 60 billion in the European Union alone. Myocardial infarction (MI) results from blockage of one of the coronary arteries that supply the cardiac tissue, leading to ischemia of a segment of the heart. This process eventually leads to the death of contractile cells and the formation of scar tissue. Since cardiomyocytes cannot proliferate, and the number of stem cells in the heart is limited, the cardiac tissue is unable to regenerate, leading to chronic cardiac dysfunction. Complications following an initial MI include heart failure, recurrent ischemia, and arrhythmias; jointly, they manifest a five-year mortality rate of near 50%. Currently, the only cure for the end-stage heart failure is cardiac transplantation. As cardiac donors are scarce, there is an urgent need to develop new strategies that will promote heart regeneration and thereby limit morbidity and mortality from this disease. Cardiac tissue engineering has evolved as an interdisciplinary field of technology combining principles from the material, engineering and life sciences with the goal of developing functional substitutes for the injured myocardium. Rather than simply introducing cells into the diseased area to repopulate the injured heart and restore function, cardiac tissue engineering involves the seeding of contracting cells in or onto 3-dimensional (3D) scaffolds prior to transplantation. Following implantation and full integration in the host, the scaffold degrades, leaving a functional cardiac patch on the defected organ. However, once the 3D cardiac patches have been engineered, the assessment of their quality in terms of electrical activity, without affecting their performance, is limited. This situation might lead to implantation of cardiac patches with limited or no potential to regenerate the infarcted heart. More importantly, the ability to monitor the performance of these patches and control their function following implantation is completely lost. The objective of this project is to expand far beyond the state-of-the-art by developing a conceptually new approach to engineer the next generation of smart cardiac patches. These patches will integrate complex electronics with engineered cardiac tissues to enable complete on-line monitoring and self-regulation of the tissue function, from the initial stage of the engineering process and through attainment of the full regeneration of the heart in the living body.

Work performed

So far, we have successfully developed and tested engineered cardiac patches that incorporate cardiac cells with flexible, free-standing electronics. The latter are integrated within 3D composite scaffolds made of synthetic or natural polymers, or from biomaterials extracted from the patient. The patches, that can be generated and processed using advanced techniques such as photolithography, electrospinning, laser patterning and 3D printing, exhibit robust electronic properties.

Final results

The patches enable the recording of cellular electrical activities and provide, for the first time, on-demand, remote interference to regulate tissue performance by provision of electrical stimulation and by releasing of drugs in the patch microenvironment. Future work will focus on the assessment of the potential of the smart cardiac patches to perform in the contexts of the living body and to improve the function of infarcted animalâ€™s hearts.