Chemoselective cross-linking of alginate with thiol-terminated peptides for tissue engineering applications

In this study we chemospecifically functionalized alginate with thiol-ended peptides for tissue engineering (TE); a carbodiimide linker and the disulfide exchange scheme were used. First carboxyls of alginate were activated by introducing N-hydroxysuccinimide (NHS) ester groups; these react with primary amines of the heterobifunctional reagent 2-(2-pyridyldithio)ethyleneamine (PDEA). Thiol-reactive alginate (alginate-S-S-py) forms as cross-linking intermediate. The degree of pyridyldithio-functionalization is modified through variable PDEA concentration and it was determined using UV–VIS spectroscopy and proton nuclear magnetic resonance. The applicability of the alginate-S-S-py as platform for the chemoselective coupling of thiol-ended peptides was tested with glutathione as model peptide. Other SH-terminal peptides were successfully cross-linked. Moreover, the peptide–alginate keeps its gel-forming ability when treated with Ca2+ cations, leading to functionalized hydrogels that can be further used to obtain different multicomponent systems. The developed chemoselective strategy of functionalizing alginate with thiol-ended peptides could enhance the potential of this polymer for TE.