Background: Acute myocardial infarction (AMI) ranks amongthe major causes of morbidity and mortality worldwide. Exceptfor heart transplantation which is limited by donation deficiencyand rejection, conventional therapies only treat the symptomsand cannot restore the damaged myocardium. Stem cell-basedtherapies represent a possible paradigm shift for cardiac repair;however, it faces several challenges. Ischemic myocardiumhas a harsh microenvironment for cell transplantation. Loss ofblood vessels, hypoxia, acidic pH and high concentration ofreactive oxygen species (ROSs) causes transplanted cell clearancewithin a monthMaterials and Methods: To enhance cell survival and propercell homing, we used two complementary methods simultaneously.First, by utilizing bifunctional core and shell-structuredmicroparticles with Hydrogen peroxide as core and Poly-lacticco-glycolic acid polymer (PLGA) as shell, short-termed oxygenationwas occurred for about two weeks. Immobilized catalaseenzyme on surface of microparticles degrades hydrogenperoxide, producing oxygen and also demolishing presentedreactive oxygen species in the microenvironment which is toxicfor cells. Second, for long-term oxygenation, we induced angiogenesisby employing fibrin-conjugated heparin injectablehydrogel for sustained delivery of angiogenic Vascularendothelialgrowth factor (VEGF). This arrangement is utmost goalbecause in one hand angiogenesis is occurred and on the otherhand during the time-consuming angiogenesis process, cells arestayed away from hypoxic effects.Results: After co-transplantation of microparticles and cardiacprogenitor cells within an angiogenic injectable hydrogel to theleft ventricle of rat AMI model, we expected significantly promotedgraft function as evidenced by histology and echocardiography.Conclusion: This study shows that exertion of oxygen generating-microparticles and induction of angiogenesis dual systemis a promising method for Increasing the survival time of transplantedcells and improvement of damaged tissue.