Preparation of Synthetic Polypeptide-PolyHIPE Hydrogels with Stimuli-Responsive Behavior

Abstract

In this work, biodegradable macroporous stimuli-responsive polypeptide hydrogels based on xmlns:oasis="http://www.niso.org/standards/z39-96/ns/oasis-exchange/table" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:ali="http://www.niso.org/schemas/ali/1.0/">l-glutamic acid (Glu) and its copolymers with equimolar amounts of xmlns:oasis="http://www.niso.org/standards/z39-96/ns/oasis-exchange/table" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:ali="http://www.niso.org/schemas/ali/1.0/">l-phenylalanine (Phe) or xmlns:oasis="http://www.niso.org/standards/z39-96/ns/oasis-exchange/table" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:ali="http://www.niso.org/schemas/ali/1.0/">l-lysine (Lys) were prepared by deprotection of the corresponding organogels under acidic conditions. The organogels were synthesized by ring-opening polymerization ofN-carboxyanhydride (NCA) derivatives of the corresponding α-amino acids in oil-in-oil high-internal phase emulsions (HIPEs) using the di-NCA derivative of xmlns:oasis="http://www.niso.org/standards/z39-96/ns/oasis-exchange/table" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:ali="http://www.niso.org/schemas/ali/1.0/">l-cystine as a cross-linker. The organogels exhibit the typical interconnected porous polyHIPE morphology, which is completely preserved in the hydrogels after removal of the protecting groups of the Glu and Lys repeating units. The pH-dependent behavior and mechanical properties of the obtained hydrogels were studied in buffer solutions with different pH values. At pH 7.5, P(Glu) and P(Glu-co-Phe) can be compressed to half their original height and both return to their initial state after unloading. By lowering the pH to 5.5, P(Glu) remains soft, while P(Glu-co-Phe) already becomes much stiffer. In contrast, for the P(Glu-co-Lys) hydrogel, high buffer uptake was observed only at high or low pH values, whereas at intermediate pH values, the low buffer uptake and the impaired ability to return to the original height are attributed to the attractive ionic interaction between the oppositely charged side groups. We have shown that by tuning the chemical composition of the polypeptides, the uptake, in vitro enzymatic degradation, and compression behavior of the hydrogels can be modulated.