Relaxation and diffusion of water protons in BDDE cross-linked hyaluronic acid hydrogels investigated by NMR spectroscopy-Comparison with physicochemical properties

Frida J Wende; Yan Xue; Gustav Nestor; Åke Öhrlund; Corine Sandström

doi:10.1016/j.carbpol.2020.116768

Relaxation and diffusion of water protons in BDDE cross-linked hyaluronic acid hydrogels investigated by NMR spectroscopy-Comparison with physicochemical properties

Carbohydr Polym. 2020 Nov 15:248:116768. doi: 10.1016/j.carbpol.2020.116768. Epub 2020 Jul 15.

Authors

Frida J Wende¹, Yan Xue², Gustav Nestor³, Åke Öhrlund⁴, Corine Sandström⁵

Affiliations

¹ Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, P.O. Box 7015, SE-750 07 Uppsala, Sweden. Electronic address: Frida.wende@slu.se.
² Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, P.O. Box 7015, SE-750 07 Uppsala, Sweden. Electronic address: Yan.xue@slu.se.
³ Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, P.O. Box 7015, SE-750 07 Uppsala, Sweden. Electronic address: gustav.nestor@slu.se.
⁴ Development Galderma, Seminariegatan 21, SE-752 28 Uppsala, Sweden. Electronic address: ake.ohrlund@galderma.com.
⁵ Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, P.O. Box 7015, SE-750 07 Uppsala, Sweden. Electronic address: corine.sandstrom@slu.se.

PMID: 32919564
DOI: 10.1016/j.carbpol.2020.116768

Abstract

Cross-linked hyaluronic acid (HA) hydrogels are used in many biomedical applications but their characterization in order to distinguish between physicochemical properties is challenging. Longitudinal (T₁) and transverse (T₂) relaxation times and diffusion coefficient (D) of water protons in diepoxide 1,4-butanediol diglycidyl ether (BDDE)-cross-linked HA hydrogels were analyzed by high-field NMR spectroscopy to distinguish between different physicochemical properties. Hydrogels of different degrees of modification and cross-linking, representing a range of gel content, swelling ability, elastic and viscous behavior were studied, as well as solutions of native HA of different molecular weights. T₁, T₂ and D were measured for several concentrations of HA and as a function of temperature. D and T₁ showed a weak concentration dependence, but did not differ between the hydrogels. T₂, dominated by chemical exchange between water protons and exchangeable protons of HA, varied significantly between the different hydrogels and the temperature profiles changed dramatically between different concentrations.

Keywords: Diffusion; Hyaluronic acid; Hydrogel; NMR; Relaxation; Water.