Spatiotemporal precision interventions for cardiac repair and regenerative therapy

Restoring cardiac function after myocardial infarction remains a major challenge, as current pharmacological and interventional therapies primarily mitigate symptoms and slow disease progression without addressing the irreversible loss of functional myocardium. Although a diverse range of biologically active agents has been developed to modulate inflammation, angiogenesis, fibrosis, and cardiomyocyte survival, their therapeutic impact is frequently limited by delivery strategies that fail to match the dynamic and heterogeneous nature of post-infarction healing. Advances in biomaterials, nanotechnology, and device engineering have enabled drug delivery systems capable of spatiotemporally programmed therapeutic engagement. By responding to injury-associated cues, recreating key features of the myocardial microenvironment, and incorporating programmable release architectures, these systems coordinate localization, release kinetics, and duration of action with distinct phases and regions of cardiac repair. When combined with appropriate delivery interfaces, including nanocarriers, injectable depots, structured platforms, and biologically derived vehicles, spatiotemporal drug delivery transforms therapy from passive administration into an active determinant of biological outcome. This Review synthesizes recent mechanistic and engineering advances to frame spatiotemporal precision as a unifying principle for cardiac drug delivery. Aligning therapeutic action with the intrinsic biology of myocardial healing provides a rational pathway toward more effective, durable, and biologically informed strategies for cardiac repair and, where biology permits, regeneration.