Stem cell therapy is an attractive approach for recovery from myocardial infarction (MI) but faces the challenges of rapid diffusion and poor survival after transplantation.Here we developed an injectable collagen scaffold to promote the long-term retention of transplanted cells in chronic MI.Forty-five minipigs underwent left anterior descending artery (LAD) ligation and were equally divided into three groups 2 months later (collagen scaffold loading with human umbilical mesenchymal stem cell (hUMSC) group,hUMSC group,and placebo group (only phosphate-buffered saline (PBS) injection)).Immunofluorescenee staining indicated that the retention of transplanted cells was promoted by the collagen scaffold.Echocardiography and cardiac magnetic resonance imaging (CMR) showed much higher left ventricular ejection fraction (LVEF) and lower infarct size percentage in the collagen/hUMSC group than in the hUMSC and placebo groups at 12 months after treatment.There were also higher densities of vWf-,αt-sma-,and cTnT-positive cells in the infarct border zone in the collagen/cell group,as revealed by immunohistochemical analysis,suggesting better angiogenesis and more cardiomyoeyte survival after MI.Thus,the injectable collagen scaffold was safe and effective on a large animal myocardial model,which is beneficial for constructing a favorable microenvironment for applying stem cells in clinical MI.