Porcine extracellular matrix hydrogel delivery incorporated with Nano-Ghosts for cardiac regeneration

Tissue engineering has been widely studied in the field of cardiac regeneration for the treatment of progressive heart failure post-myocardial infarction, presenting new biomaterials as a therapeutic approach that may delay disease progression and possibly regenerate the scar tissue. As a biomaterial for tissue engineering, porcine extracellular matrix (pECM) has gained a growing attention, due to its intrinsic scaffolding properties, and which comprising the natural cell environment within tissues. Injectable scaffolds offer the prospective advantage of minimally invasive administration, directly into the myocardium, and the possible delivery of bioactive compounds and cells. We have previously developed an injectable pECM-based hydrogel that was shown to support the cultivation of mesenchymal stem cells (MSCs) and human induced pluripotent stem cells (hiPSCs) in vitro and to improve cardiac function in rat models in vivo.

In the present study, we hypothesized that cardiac pECM hydrogel delivering hiPSCs and pro-regenerative compounds will provide an optimal scaffold for cardiac tissue regeneration. The Nano-Ghosts (NGs) are vesicles, which are derived from the cell membranes of MSCs, and as such, maintain the MSCs membrane characteristics. The NGs were incorporated into the cardiac pECM hydrogel and may serve to promote regenerative processes. Moreover, they can be used to deliver a drug of choice, as well as growth factors to the infarct area. The cardiac pECM hydrogel was shown to support the culture of MSCs and hiPSCs and to affect the cell morphology. In addition, the differentiation of hiPSCs on the cardiac pECM hydrogel was enhanced towards the cardiac lineage, when introduced with or without the NGs. Furthermore, NGs were shown to be uptaken by the hiPSCs, dispersed evenly when mixed in the pECM hydrogel, and additionally were proved to modulate processes of inflammation.

To conclude, we propose a composite platform of cardiac pECM hydrogel combining the delivery of hiPSCs and the novel NGs delivery system, holding the potential for improved personalized cardiac regenerative medicine.