Dysfunction or loss of blood vessel causes several ischemic diseases. Although endothelial progenitor cells (EPCs) are a promising source for cell-based
therapy,
ischemia-induced pathophysiological condition limits the recovery rate by causing drastic cell death. To overcome this issue, we attempted to develop a cell-targeted
peptide delivery and priming system to enhance
EPC-based neovascularization using an engineered M13 bacteriophage harboring nanofibrous tubes displaying ~2700 multiple functional motifs. The M13 nanofiber was modified by displaying RGD, which is an
integrin-docking
peptide, on the minor coat
protein, and by mutilayering SDKP motifs, which are the key active sites for
thymosin β4, on the major coat
protein. The engineered M13 nanofiber dramatically enhanced ischemic neovascularization by activating intracellular and extracellular processes such as proliferation, migration, and tube formation in the EPCs. Furthermore,
transplantation of the primed EPCs with the M13 nanofiber harboring RGD and SDKP facilitated functional recovery and neovascularization in a murine hindlimb
ischemia model. Overall, this study demonstrates the effectiveness of the M13 nanofiber-based novel
peptide delivery and priming strategy in promoting
EPC bioactivity and neovessel regeneration. To our knowledge, this is first report on M13 nanofibers harboring dual functional motifs, the use of which might be a novel strategy for stem and progenitor cell
therapy against cardiovascular ischemic diseases.