Stem cells and nanomaterials for cardiac regeneration: integrating multi-omics for precision therapeutics.

Cardiovascular diseases (CVDs) are one of the leading causes of mortality worldwide, with myocardial infarction (MI) resulting in irreversible loss of cardiomyocytes and progressive cardiac dysfunction. Clinical interventions primarily restore perfusion and alleviate symptoms yet fail to regenerate the damaged myocardium. Stem cell-based therapeutics have emerged as effective and promising regenerative strategies, largely mediated through paracrine signaling, immunomodulation, and cellular replacement. However, poor cell survival, inadequate engraftment, and functional immaturity of stem cell-derived cardiomyocytes limits their clinical efficacy. Advances in nanotechnology and multi-omics provide powerful tools to address these challenges. Nanomaterials such as gold nanoparticles, graphene derivatives, and MXenes enhance stem cell retention, survival, and electromechanical integration by mimicking the native ECM and enabling targeted delivery of therapeutic molecules. Concurrently, transcriptomic and proteomic profiling offer insights into mechanisms of stem cell-mediated cardiac repair and molecular pathways governing their behavior. Stem cell-based clinical trials demonstrate modest therapeutic benefits, emphasizing the need for integrative, precision-driven strategies. The convergence of stem cell biology, nanomaterial engineering, and multi-omics technologies represents transformative approaches to overcoming limitations and advancing cardiovascular regeneration. This integrative framework holds potential to enable data-driven, personalized therapies to improve functional recovery and long-term outcomes in patients with CVDs.