Recent advances in the production of human cardiomyocyte surrogates, particularly those derived from induced-pluripotent stem cells (iPSC-cardiomyocytes), represented a game changer in the field of cell therapy for the treatment of cardiac injury, showing potential reduction in cardiomyocyte apoptosis and infarct size in pre-clinical infarct models. While iPSC-derived cardiomyocyte surrogates do not give rise to ethical concerns and closely resemble the physiology and function of mature cardiomyocytes, their electromechanical activity is still rudimentary. Therefore, the most evident clinical limitations observed in pre-clinical studies using cardiomyocyte surrogates are the absence of cardiac coupling with the host tissue and poor cell retention.
Previously, conductive materials have been used to attempt electrical coupling. Although there is no evidence yet for electrical coupling with cardiomyocytes, these have shown to interact electrically with the myocardial tissue. Also, their limited mechanical performance, biocompatibility and electrical stability need to be addressed to make these materials a feasible clinical approach for cardiac repair. The aim of this project was to achieve cardiomyocyte electrical coupling using conductive hydrogels as scaffolds for iPSC-cardiomyocyte implantation. Since the materials would be intended towards clinical use, I aimed to synthesize a biocompatible material and tune the mechanical properties of the hydrogel to match those of the myocardium. An important objective was to study the electrical properties and stability of the resulting material, followed by the development of an electro-stimulation device to pace and study the electrophysiology of cardiomyocytes interfacing the conductive material.
By the end of this action, a conductive biomaterial based on PEDOT-derivatives was developed, which can be easily injected and form hydrogels in the heart tissue. The mechanical and electrical properties of the material match those reported in the heart. The conductive hydrogels were biocompatible and were deemed to be a suitable material to facilitate pacing of iPSC-cardiomyocytes, compared to conventional hydrogel scaffolds. This project was performed in close collaboration with the British Heart Foundation at Imperial College London, and the outcomes of this project will advance this technology further into clinically relevant infarct models for the implantation of cardiomyocytes surrogates for the treatment of cardiac infarct.
