Cardiovascular diseases continue to be the leading cause of death in the western world, calling for new treatments for progressive heart failure, post myocardial infarction. In the past two decades, tissue engineering (TE) was suggested as a therapeutic approach that may delay disease progression and possibly regenerate the scar tissue. While acellular and cellular cardiac patches are applied surgically to the epicardial surface of the heart, injectable biomaterials offer the prospective advantage of minimally invasive delivery, directly into the myocardium.
In our study, we hypothesize that liquidizing porcine cardiac extracellular matrix (pcECM) could serve as ideal injectable scaffold for cardiac tissue engineering. Acellular ECM is the closest to mimic the natural cell surrounding, as it is bioactive, biodegradable and biocompatible. Most importantly, it provides the cells with the right environmental and chemical cues, which are crucial for the new construct integration to the host.
We have developed various pcECM-based gel formulations which all support cell viability and proliferation (mesenchymal stem cells-MSCs and human induced pluripotent stem cells-hiPSCs) and differ in their mechanical properties. Furthermore, the pcECM-based gels were shown to affect cell morphology as well as to enhance differentiation towards the cardiac linage. Following, the gel`s biocompatibility was comprehensively demonstrated in vitro and in vivo in mice model. Finally, the therapeutic efficacy of this injectable scaffold was demonstrated both in acute and chronic MI rat models, representing two distinct treatment scenarios. In these models, our pcECM-based gels enabled not only preservation, but also improvement in cardiac function.
To conclude, injectable pcECM-based materials offer minimally invasive platform for heart regeneration with and without cells. Furthermore, the unique ability to cultivate hiPSCs and their derivative within such construct may substantially contribute to the cardiac engineering field of personalized medicine.
