Engineering Nanoparticles and Bioscaffolds for Targeted microRNA Delivery in Cardiovascular Regeneration—A Comprehensive Review

Cardiovascular diseases, particularly myocardial infarction (MI), remain a leading cause of mortality worldwide, primarily due to the extensive loss of cardiomyocytes and the heart's limited regenerative capacity. MI, caused by obstructed blood flow, results in cardiac muscle damage, scar tissue formation, and ultimately, heart failure. While heart transplantation is the definitive treatment, its application is limited by donor shortages and the risk of immune rejection. This underscores the urgent need for regenerative strategies. MicroRNAs (miRNAs) play a crucial role in regulating myocardial healing post-ischemia, with specific miRNAs such as miR-92a, miR-126, and miR-145 shown to promote angiogenesis. However, the therapeutic application of miRNAs is hindered by delivery challenges at both extracellular and intracellular levels. This review explores the potential of nanoparticles (NPs) and engineered bioscaffolds to address these obstacles. We first examine the role of miRNAs in post-MI cardiovascular remodeling, followed by an overview of current challenges in miRNA-based therapy delivery. We then discuss the use of NPs and electrospun nanofibrous scaffolds in this context. Finally, we review existing cardiac bioscaffolds, their limitations, and future directions for developing optimized nanofibrous scaffolds for effective cardiac regeneration.