Design and characterization of an injectable hydrogel for miRNA release

Cardiovascular disease (CVDs) are the major cause of morbidity and mortality worldwide. Among these pathologies, myocardial infarction (MI) is responsible for 85% of the deaths concerning CVDs, leading to a significant loss of contractile cardiomyocytes and tissue remodelling with the formation of a fibrotic scar. The release of specific microRNA (miRNAs) has arisen considerable interest as a new strategy for myocardial regeneration, inducing cardiomyocytes proliferation or transdifferentiation of cardiac fibroblasts into induced cardiomyocytes (iCMs). However, the delivery of naked miRNAs has different drawbacks associated with low retention at the targeted site and possible off-target effects. Injectable hydrogels have been proposed as a promising alternative for the controlled and local in situ release of encapsulated miRNAs-loaded nanoparticles. In this thesis project, a modified alginate-based injectable hydrogel was prepared for the in situ gradual release of miRNAs-loaded polymer nanoparticles (NPs), for heart regeneration. NPs loaded with negmiR or miRcombo were obtained according to a method under patenting. NPs were physically entrapped within the hydrogel matrix and the system was physicochemically and biologically characterized using adult human cardiac fibroblasts (AHCFs). The work has been carried out within the BIORECAR ERC project (grant agreement 772168).