Controlled rheological behaviors of hyaluronic acid solutions through attractive polymeric micelle-mediated interchain association

Herein, we report a facile but straightforward way to control the rheological properties of hyaluronic acid (HA) solutions by taking advantage of the interchain association of electrostatically attractive polymeric micelles (APMs). For this, we synthesized an amphiphilic triblock copolymer, poly(2-aminoethyl methacrylate)-block-poly(3-caprolactone)-block-poly(2-aminoethyl methacrylate) (PAMA-b-PCL-b-PAMA), via atomic transfer radical polymerization and co-assembled it with amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) to produce APMs with cationic charges. The incorporation of the APMs into a gel-type HA solution not only readily transitioned the viscous flow to elastic flow but also easily led to the deformation of the gel microstructure in response to the shear rate, which is comparable to the case of a linear HA solution. We identified that the unique rheological behavior of the gel-type HA solutions stemmed from the APM-mediated particulate crosslinking. Finally, we demonstrated that the fine tuning of the interchain association by manipulation of the electrostatic interaction between APMs and HA molecules enabled the diversification of the rheological properties of HA solutions, making this system a promising hydrogel rheology controller.