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

Abstract

In this work, biodegradable macroporous stimuli-responsive polypeptide hydrogels based on L-glutamic acid (Glu) and its copolymers with equimolar amounts of L-phenylalanine (Phe) or L-lysine (Lys) were prepared by deprotection of the corresponding organogels under acidic conditions. The organogels were synthesized by ring-opening polymerization of Ncarboxyanhydride (NCA) derivatives of the corresponding α-amino acids in oil-in-oil high-internal phase emulsions (HIPEs) using the di-NCA derivative of 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 pHdependent 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.

Rational construction of polycystine-based nanoparticles for biomedical applications

“…Recently, a high yield (B83%) of Cys 2 NCA via the two-step Fuchs-Farthing method was achieved using di-N-tert-butyloxycarbonyl-L-cystine (Boc-Cys 2 -OH) as the reactant, which was highly soluble in anhydrous ethyl acetate. 18,19 Since Boc-Cys 2 -OH is commercially available, the alternative Fuchs-Farthing strategy showed significant advantages compared with traditional methods.…”

“…17 The addition of PLys and PGlu segments could make the core positively or negatively charged under physiological conditions, significantly enhancing the encapsulation of portable cargos. 19 For example, copolymerization with Glu increased the DLE of DOX up to 96% by simply mixing in an aqueous solution, avoiding the additional removal of organic solvents. 38 In another study, DOX and the hydrophobic drug resveratrol (RES) were loaded into the PGlu-containing nanogel separately.…”

Self-assembled silk fibroin hydrogels: from preparation to biomedical applications

“…3,4 Hydrogels are water-swollen three-dimensional viscoelastic macromolecular networks, crosslinked through either covalent bonds or non-covalent interactions such as electrostatic interactions, hydrogen bonding, hydrophobic association, and multivalent coordination. 5,6 Hydrogels have attracted extensive attention due to their versatility in composition, preparation, and resulting tunable properties such as swelling capacity, an interfacial affinity for target compounds, stimuli response, degradability, viscoelasticity, and network architecture. 7,8 Polymeric hydrogels have been used as functional materials in a variety of applications.…”

Synthetic Polypeptide–Polyester PolyHIPEs Prepared by Thiol–Ene Photopolymerization

“…Another class of polymers that are characterized by a suitable microenvironment for cell growth and can incorporate various functional groups into the structure is synthetic polypeptides prepared by ring-opening polymerization (ROP) of N -carboxyanhydrides (NCAs). , Synthetic polypeptide scaffolds are usually prepared in the form of microporous hydrogels, − while macroporosity can be achieved by cryogelation , or porogen leaching . In our previous work, we have shown that polyHIPEs based on either synthetic polypeptides , or semicrystalline PCL can be prepared by ROP of NCAs or ε-caprolactone (CL), respectively, in the continuous phase of HIPE, resulting in two chemically and mechanically very different materials. However, due to the different reactivity of NCAs and lactone monomers as well as the nature of their propagating species, they cannot be readily copolymerized into corresponding poly­(ester-amides).…”