Designer functionalized self-assembling peptide nanofiber scaffolds for growth, migration, and tubulogenesis of human umbilical vein endothelial cells

We previously reported a class of designer self-assembling peptide nanofiber scaffolds as a unique biological material for diverse applications including 3-D tissue cell culture, slow drug release, regenerative medicine, and tissue engineering. One of these peptide scaffolds, RADA16-I has been used in bone, cartilage, and neural regeneration studies that have shown great promises. We here report the development of two new functionalized self-assembling peptide nanofiber scaffolds designed specifically for angiogenesis study through directly coupling pure RADA16-I with short biologically angiogenic motifs. Angiogenesis is very important in regenerative medicine. An adequate blood vessel supply to the newly formed tissue and within the transplanted scaffold is essential in determining the success of new tissue regeneration. In our study, two designer functionalized peptides, KLT, Ac–(RADA)4G4KLTWQELYQLKYKGI–CONH2 and PRG, Ac–(RADA)4GPRGDSGYRGDS–CONH2 significantly enhanced endothelial cell survival, proliferation, migration, and morphological tubulogenesis compared with unmodified RADA16-I scaffold. We also showed in our clear-boundary sandwich culture without adding extract soluble growth factors that cells migrated uni-directionally from RADA16-I toward the functionalized scaffolds but not the reverse. Our results suggest that the functionalized designer peptide scaffolds will not only have great promise for promoting endothelial cell growth, migration, and tubulogenesis, but also may have widely potential applications for diverse tissue engineering and tissues regeneration.