Self-healing hyaluronic acid/polylysine hydrogel prepared by dual-click chemistry from polyrotaxane slidable crosslinkers

Abstract

A new type of pH-sensitive hydrogel containing supramolecular structures was fabricated from maleimide-functionalized polyrotaxane, ɛ-polylysine and furan-functionalized hyaluronic acid by Diels-Alder reaction and amino-maleimide reaction. Firstly, pseudo polyrotaxane was obtained through self-assembly of polyethylene glycol and α-cyclodextrin, and then capped with 1-adamantanecarboxylic acid to convert it into polyrotaxane. Secondly, a maleimide-functionalized slidable crosslinker was obtained by modifying the polyrotaxane with 3-maleimide propionic acid, and furan-functionalized hyaluronic acid was prepared by modifying it with 2-furanmethylamine. Thirdly, the hydrogel cotaining supramolecular structures was fabricated from the prepared slidable crosslinker, ɛ-polylysine, and furan-functionalized hyaluronic acid in mixed solvent of water and N,N-dimethylformamide. Taking gel mass fraction and swelling ratio as two indicators, the formation parameters of hydrogel were optimized through single- factor experiments. The pH-sensitivity, rheological properties, self-healing performance, and degradation behavior of the hydrogel were investigated. Cytotoxicity assay, live/dead stains, and hemolysis assay were done to verify the biocompatibility of the hydrogel. Finally, the slow-release behavior of the hydrogel containing lidocaine hydrochloride was studied. The hydrogel possesses good biocompatibility, pH-sensitivity, self-healing behavior, degradation, and drug-controlled release, and can find broad application in biomaterials.

Keywords: Amino-maleimide reaction; Diels-Alder reaction; Host–guest interaction; Polyrotaxane; Self-healing; Slow release.