Injectable Self-Healing Hydrogels Based on Boronate Ester Formation between Hyaluronic Acid Partners Modified with Benzoxaborin Derivatives and Saccharides

Biomacromolecules. 2020 Jan 13;21(1):230-239. doi: 10.1021/acs.biomac.9b01128. Epub 2019 Oct 14.

Abstract

We demonstrate here, for the first time, formation of injectable dynamic covalent hydrogels at physiological pH using benzoxaborin-saccharide complexation as a reversible cross-linking method. The gels were prepared by simply mixing hyaluronic acid modified with an original boronic acid derivative, 3,4-dihydro-2H-benzo[e][1,2]oxaborinin-2-ol (1,2-ABORIN), and HA functionalized with 1-amino-1-deoxy-d-fructose. Dynamic rheological experiments confirmed the gel-like behavior (storage modulus (G') > loss modulus (G″) in the frequency window explored) for the designed HA-1,2-ABORIN/HA-fructose network. Furthermore, this hydrogel exhibited excellent self-healing and injectability behaviors in aqueous conditions and was found to be responsive to pH. Additionally, fibroblast cells encapsulated in the HA network showed high viability (>80% after 7 days of cell culture), as monitored by Live/Dead staining. Taken together, this new class of boronate ester cross-linked hydrogel provides promising future for diverse biomedical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Borinic Acids / chemistry
  • Boronic Acids / chemistry
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods*
  • Cell Survival
  • Fibroblasts / cytology
  • Fructose / chemistry
  • Hyaluronic Acid / chemistry*
  • Hydrogels / chemistry*
  • Hydrogen-Ion Concentration
  • Injections
  • Magnetic Resonance Spectroscopy
  • Mice
  • Rheology

Substances

  • Borinic Acids
  • Boronic Acids
  • Hydrogels
  • Fructose
  • Hyaluronic Acid
  • benzeneboronic acid