Stem cell based therapy is coming of age. Besides stem cell transplantation, it has been a goal to use native autologous stem cells for tissue regeneration. However, the recruitment of native autologous stem cells at the targeting site has not been sufficient which limits the clinical application of autologous stem cells. Biomaterials have been increasingly used in tissue repair. They not only serve as scaffolds for cell proliferation, differentiation, and also provide guidance for 3-D reestablishment. In this study, we have attempted to enrich autologous stem cells at the wound site through a stem-cell-capturing collagen scaffold by conjugating with a stem cell specific antibody. Sca-1 is a common surface marker of hematopoietic, cardiac and skeletal muscle stem cells. Due to the interaction of antibody and antigen, Sca-1 positive cells could be enriched to the functional collagen scaffold both in vitro and in vivo. When the functional collagen scaffold is transplanted into C57/BL6 mouse as a patch to repair a surgical heart defect, the regeneration of cardiomyocytes has been observed. Thus, the collagen scaffolds covalently conjugated with stem cell specific antibody could be an effective approach to promote tissue regeneration.