pH-Sensitive Poly(acrylic acid)-g-poly(L-lysine) Charge-Driven Self-Assembling Hydrogels with 3D-Printability and Self-Healing Properties.

We report the rheological behavior of aqueous solutions of a graft copolymer polyampholyte, constituted of polyacrylic acid (PAA) backbone grafted by Poly(L-lysine) (PAA-b-PLL). The graft copolymer self-assembles in aqueous media, forming a three-dimensional (3D) network through polyelectrolyte complexation of the oppositely charged PAA and PLL segments. Rheological investigations showed that the hydrogel exhibits interesting properties, namely, relatively low critical gel concentration, elastic response with slow dynamics, remarkable extended critical strain to flow, shear responsiveness, injectability, 3D printability and self-healing. Due to the weak nature of the involved polyelectrolyte segments, the hydrogel properties display pH-dependency, and they are affected by the presence of salt. Especially upon varying pH, the PLL secondary structure changes from random coil to α-helix, affecting the crosslinking structural mode and, in turn, the overall network structure as reflected in the rheological properties. Thanks to the biocompatibility of the copolymer constituents and the biodegradability of PLL, the designed gelator seems to exhibit potential for bioapplications.

Synthesis and Characterization of the Novel Nε-9-Fluorenylmethoxycarbonyl-l-Lysine N-Carboxy Anhydride. Synthesis of Well-Defined Linear and Branched Polypeptides.

The synthesis of well-defined polypeptides exhibiting complex macromolecular architectures requires the use of monomers that can be orthogonally deprotected, containing primary amines that will be used as the initiator for the Ring Opening Polymerization (ROP) of N-carboxy anhydrides. The synthesis and characterization of the novel monomer Nε-9-Fluorenylmethoxycarbonyl-l-Lysine N-carboxy anhydride (Nε-Fmoc-l-Lysine NCA), as well as the novel linear Poly(Nε-Fmoc-l-Lys)n homopolypeptide and Poly(l-Lysine)78-block-[Poly(l-Lysine)10-graft-Poly(l-Histidine)15] block-graft copolypeptide, are presented. The synthesis of the graft copolypeptide was conducted via ROP of the Nε-Boc-l-Lysine NCA while using n-hexylamine as the initiator, followed by the polymerization of Nε-Fmoc-l-Lysine NCA. The last block was selectively deprotected under basic conditions, and the resulting ε-amines were used as the initiating species for the ROP of Nim-Trityl-l-Histidine NCA. Finally, the Boc- and Trt- groups were deprotected by TFA. High Vacuum Techniques were applied to achieve the conditions that are required for the synthesis of well-defined polypeptides. The molecular characterization indicated that the polypeptides exhibited high degree of molecular and compositional homogeneity. Finally, Dynamic Light Scattering, ζ-potential, and Circular Dichroism measurements were used in order to investigate the ability of the polypeptide to self-assemble in different conditions. This monomer opens avenues for the synthesis of polypeptides with complex macromolecular architectures that can define the aggregation behavior, and, therefore, can lead to the synthesis of "smart" stimuli-responsive nanocarriers for controlled drug delivery applications.