Thermosensitive hydrogel from oligopeptide-containing amphiphilic block copolymer: effect of peptide functional group on self-assembly and gelation behavior.

We reveal that a slight change in the functional group of the oligopeptide block incorporated into the poloxamer led to drastically different hierarchical assembly behavior and rheological properties in aqueous media. An oligo(L-Ala-co-L-Phe-co-β-benzyl L-Asp)-poloxamer-oligo(β-benzyl-L-Asp-co-L-Phe-co-L-Ala) block copolymer (OAF-(OAsp(Bzyl))-PLX-(OAsp(Bzyl))-OAF, denoted as polymer 1), which possessed benzyl group on the aspartate moiety of the peptide block, was synthesized through ring-opening polymerization. The benzyl group on aspartate was then converted to carboxylic acid to yield oligo(L-Ala-co-L-Phe-co-L-Asp)-poloxamer-oligo(L-Asp-co-L-Phe-co-L-Ala) (OAF-(OAsp)-PLX-(OAsp)-OAF, denoted as polymer 2). Characterization of the peptide secondary structure in aqueous media by circular dichroism revealed that the oligopeptide block in polymer 1 exhibited mainly an α-helix conformation, whereas that in polymer 2 adopted predominantly a β-sheet conformation at room temperature. The segmental dynamics of the PEG in polymer 1 remained essentially unperturbed upon heating from 10 to 50 °C; by contrast, the PEG segmental motion in polymer 2 became more constrained above ca. 35 °C, indicating an obvious change in the chemical environment of the block chains. Meanwhile, the storage modulus of the polymer 2 solution underwent an abrupt increase across this temperature, and the solution turned into a gel. Wet-cell TEM observation revealed that polymer 1 self-organized to form microgel particles of several hundred nanometers in size. The microgel particle was retained as the characteristic morphological entity such that the PEG chains did not experience a significant change of their chemical environment upon heating. The hydrogel formed by polymer 2 was found to contain networks of nanofibrils, suggesting that the hydrogen bonding between the carboxylic acid groups led to an extensive stacking of the β sheets along the fibril axis at elevated temperature. The in vitro cytotoxicity of the polymer 2 aqueous solution was found to be low in human retinal pigment epithelial cells. The low cytotoxicity coupled with the sol-gel transition makes the corresponding hydrogel a good candidate for biomedical applications.