Liquid crystalline composite hydrogels with large pH-triggered anisotropic swelling for embolotherapy

Abstract

Inspired by the anisotropic structure of biological tissues, anisotropic hydrogels have been developed using various nanofillers, however, it remains a big challenge to synthesize hydrogels with large swelling anisotropy. Herein a single molecule filler, α-helical polypeptide, instead of nanoscale fillers, was used to synthesize anisotropic hydrogels. First nematic liquid crystal of poly(γ-benzyl l-glutamate) (PBLG) was prepared by shearing and stabilized by embedding in a crosslinked polymer matrix. The resulting PBLG composite gels were then converted to poly(L-glutamic acid) (PLGA) composite gels by debenzylation. The rigid rod-like structure of α-helical PBLG chains makes them easy to be orientated. The pH-sensitivity of PLGA makes the resulting composite gels pH-sensitive without the need to couple with a stimuli-responsive hydrogel matrix. In response to pH change PLGA composite gels swell anisotropically with a much larger swelling degree in the radial direction than in the axial direction. The swelling anisotropy (3.43) is much higher than most anisotropic hydrogels, particularly the stimuli-responsive ones reported previously. The composite gel also exhibits anisotropic mechanical properties with a larger Young's modulus in the axial direction than that in the radial direction. Preliminary test demonstrated that the composite gels have potential in embolotherapy thanks to its large pH-triggered anisotropic swelling. Statement of SignificanceAnisotropic hydrogels have important biomedical applications. Introduction of oriented nanofillers has been demonstrated a popular and versatile method for their synthesis, however, it remains a big challenge to achieve large swelling anisotropy. Herein a single molecule filler, α-helical polypeptide, instead of nanoscale fillers, was used to synthesize anisotropic hydrogels. This filler can be easily oriented by shearing. More importantly, as single molecule filler, it can constrain the swelling of hydrogel matrix more effectively. Using this filler, a pH-sensitive hydrogel with large swelling anisotropy (3.43) was successfully synthesized. Thanks to its large pH-triggered anisotropic swelling the hydrogel was successfully used as embolic agent to occlude vessels.