Precision immunomodulation of viral myocarditis: a spatiotemporal intervention paradigm based on smart biomaterials

Viral myocarditis (VMC) represents a primary etiology of sudden cardiac death (SCD) in young populations and significantly contributes to the development of dilated cardiomyopathy (DCM). The clinical prognosis of VMC is contingent upon the precise orchestration of pathogen clearance and the prevention of deleterious immune activation. Disease progression is characterized by multifaceted immunometabolic reprogramming, regulated cell death (RCD) pathways (including pyroptosis and ferroptosis), and complex crosstalk between damaged cardiomyocytes and infiltrating immune cells. However, conventional broad-spectrum immunosuppressants often fail to provide substantial clinical benefits due to a lack of spatiotemporal specificity, which complicates the delicate balance between anti-inflammatory efficacy and the preservation of antiviral immunity. This review delineates the paradigm shift in VMC therapeutic strategies, transitioning from systemic pharmacotherapy toward precision immunomodulation mediated by advanced biomaterials, such as functionalized cardiac patches, engineered exosomes, and piezoelectric materials. By integrating breakthroughs in immunology and bioengineering, these emerging platforms offer a promising avenue for targeted intervention during the early stages of VMC. Such approaches aim to suppress pathological inflammation without compromising intrinsic antiviral capacity, ultimately preventing the progression from acute VMC to irreversible heart failure.