Natural Product-Derived Hydrogels for Myocardial Infarction Repair: Mechanisms, Challenges, and Translational Perspectives

Abstract Myocardial infarction (MI) remains a leading cause of death worldwide, yet current therapeutic interventions offer limited capacity for functional cardiac regeneration. In recent years, hydrogels derived from natural products have emerged as compelling therapeutic platforms, attributed to their favorable biocompatibility, tunable biodegradability, and intrinsic biological activities. This review systematically summarizes natural product-derived hydrogels for MI repair, with particular emphasis on representative polysaccharide-based systems, including chitosan, alginate, and hyaluronic acid. It also discusses small-molecule self-assembled hydrogels, such as glycyrrhizic acid, puerarin, and rhein, as well as hydrogel-based extracellular vesicle delivery systems, as complementary therapeutic strategies. We further highlight the multifaceted mechanisms through which these materials ameliorate the pathological cardiac microenvironment, including structural reinforcement, restoration of electrical conduction, modulation of the immune response, promotion of neovascularization, and scavenging of reactive oxygen species. Critical challenges impeding clinical translation, such as long-term biocompatibility, targeted delivery efficiency, and scalable manufacturing, are thoroughly examined, alongside emerging directions including stimuli-responsive systems and three-dimensional bioprinting technologies. Although natural product-derived hydrogels hold considerable promise for cardiac repair, overcoming existing technical hurdles through continued interdisciplinary research remains imperative for their successful transition from bench to bedside.