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Although numerous studies demonstrated that localized delivery of either cells or biomaterials improved postinfarction cardiac function, the underlying mechanisms for this effect remain unclear. We performed a comparison of the effects of fetal, neonatal, and human embryonic stem cell-derived cardiac cell as well as mesenchymal stem cell transplantation versus biomaterial (collagen/ extracellular matrix) implantation therapy in rat myocardial infarction model in our laboratory, specifically comparing their effects on infarct wall thickness, neovascularization, infarct wall motion, and left ventricular ejection fraction (LVEF). Both cell and biomaterial treatment had similar beneficial effects on cardiac structure (increasing infarct wall thickness and preventing infarct expansion) and function (preventing paradoxical LV systolic bulging and improving LVEF). In this review, we also discussed the underlying mechanisms of cell and biomaterial therapies, their advantages and disadvantages, and future research directions in the field of regenerative cardiology.