Effect of Carboxymethylation on the Rheological Properties of Hyaluronan

PLoS One. 2016 Sep 9;11(9):e0162849. doi: 10.1371/journal.pone.0162849. eCollection 2016.

Abstract

Chemical modifications made to hyaluronan to enable covalent crosslinking to form a hydrogel or to attach other molecules may alter the physical properties as well, which have physiological importance. Here we created carboxymethyl hyaluronan (CMHA) with varied degree of modification and investigated the effect on the viscosity of CMHA solutions. Viscosity decreased initially as modification increased, with a minimum viscosity for about 30-40% modification. This was followed by an increase in viscosity around 45-50% modification. The pH of the solution had a variable effect on viscosity, depending on the degree of carboxymethyl modification and buffer. The presence of phosphates in the buffer led to decreased viscosity. We also compared large-scale production lots of CMHA to lab-scale and found that large-scale required extended reaction times to achieve the same degree of modification. Finally, thiolated CMHA was disulfide crosslinked to create hydrogels with increased viscosity and shear-thinning aspects compared to CMHA solutions.

MeSH terms

  • Biopolymers / chemistry
  • Buffers
  • Cross-Linking Reagents / chemistry
  • Electric Conductivity
  • Gels / chemistry
  • Hyaluronic Acid / chemical synthesis
  • Hyaluronic Acid / chemistry*
  • Hydrogen-Ion Concentration
  • Methylation
  • Molecular Weight
  • Rheology*
  • Solutions
  • Spectroscopy, Fourier Transform Infrared
  • Sulfhydryl Compounds / chemistry
  • Viscosity

Substances

  • Biopolymers
  • Buffers
  • Cross-Linking Reagents
  • Gels
  • Solutions
  • Sulfhydryl Compounds
  • Hyaluronic Acid

Grants and funding

RW was supported by an Undergraduate Research Opportunities Program award from the University of Utah. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The remaining authors received no specific funding for this work. SentrX Animal Care provided support in the form of salaries for authors AC, SKA, and BKM, and research materials, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.