Advances in Smart Hydrogels for Myocardial Infarction Therapy: A Scoping Review of Applications, Challenges, and Future Perspectives.

Smart hydrogels are stimuli-responsive biomaterials that enable targeted, sustained, and controlled therapeutic delivery. Their unique ability to respond to physiological cues such as pH, temperature, reactive oxygen species (ROS), and enzymatic activity makes them highly attractive for myocardial infarction (MI) therapy. This scoping review explores advances, applications, challenges, and future perspectives related to the use of smart hydrogels in MI. An initial comprehensive search of PubMed, Scopus, and ScienceDirect yielded 1802 records, from which 32 studies published between 2011 and 2025 met the inclusion criteria under the PRISMA-ScR framework. An updated search identified seven additional eligible studies, bringing the total to 39 included studies. These studies primarily focused on smart hydrogels for delivering bioactive agents, including growth factors, stem cells, exosomes, and nanoparticles, to enhance myocardial regeneration and repair. Evidence from preclinical models consistently demonstrated improvements in myocardial remodeling, angiogenesis, cell survival, and functional cardiac recovery. Despite these encouraging findings, several important limitations were identified. Studies relied on short evaluation periods, lacked long-term follow-up, and were restricted to small-animal models, thereby limiting the robustness of translational insights. Large-animal studies and early clinical investigations remain scarce, highlighting the gap between experimental progress and clinical application. Nonetheless, smart hydrogels stand out as a promising therapeutic platform because of their capacity for localized, adaptive, and sustained responses within the complex postinfarct microenvironment. Future work should prioritize long-term efficacy studies, development of minimally invasive delivery methods, and the use of clinically relevant preclinical models to better facilitate translation to human MI therapy.