Improved exposure of bioactive peptides to the outermost surface of the polylactic acid nanofiber scaffold

We recently reported a novel method to modify the polylactic acid (PLLA) nanofiber scaffold with IKVAV peptide/oligo (d-lactic acid) (ODLA) heteroconjugates. However, a part of the IKVAV sequence was not exposed to the outermost surface and therefore, cell adhesion was not optimized. In this study, we evaluated two strategies to improve the exposing efficiency of IKVAV. One strategy introduced a hydrophilic diethylene glycol (diEG) segment between IKVAV and ODLA. In the second method, these modified nanofibers were heated to a given temperature and cooled to room temperature in water. The IKVAV peptides at the outermost surface were quantified by the fluorescein isothiocyanate staining method. After being heated above the PLLA glass transition temperature, the exposing efficiency of the IKVAV sequence on the PLLA/ODLA-diEG-IKVAV nanofiber was three times higher than that on the PLLA/ODLA-IKVAV unheated nanofiber. Moreover, nearly 100% of the PC-12 cells seeded onto the PLLA/ODLA-diEG-IKVAV nanofiber and were well distributed, while only 50% of the PC-12 cells seeded onto the PLLA and PLLA/ODLA-IKVAV nanofibers. These strategies markedly enhanced the exposing efficiency of the bioactive peptides; therefore, their use can be applicable to other nanofiber scaffolds.