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Doctoral thesis, 2019

Structural Studies of Hyaluronan Hydrogels

Wende, Frida


Hydrogels consist of cross-linked polymer networks with the ability to absorb large amounts of water. In this thesis, the structures of hydrogels consisting of hyaluronic acid (HA) cross-linked by 1,4-butanediol diglycidyl ether (BDDE) have been investigated. Hyaluronic acid is a naturally occurring polysaccharide that is abundant in the extracellular matrix of all vertebrates. Due to high viscoelasticity and biocompatibility, hyaluronic acid based hydrogels have many biomedical applications. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), which are among the most important analytical techniques for analysis of organic compounds and biomacromolecules, were used for analysis of structural properties of HA-BDDE hydrogels. NMR- and MS-based methods were developed to determine the positions of substitution of the cross-linker on HA in fragments obtained from enzymatic degradation of HA-BDDE hydrogels. One-dimensional proton and carbon NMR methods were then further developed for quantitative analysis of substitution positions, degree of modification and degree of cross-linking. No chromatographic separation step was needed. Desulphated chondroitin has a primary structure that only differs from that of HA by the configuration at C4 of the aminoglycan. The reactivity of desulphated chondroitin towards BDDE as well as alkali-induced changes in chemical shifts were determined and compared to that of hyaluronic acid. Using NMR spectroscopy of hydroxyl protons, hydrogen bonding in the two polymers were compared. Water is the most abundant component of the studied hydrogels. Using NMR spectroscopy, the relaxation and diffusion behaviour of water protons in native HA solutions and cross-linked HA hydrogels with different physicochemical properties were studied. The transverse relaxation, which is dominated by chemical exchange, could be correlated to polysaccharide mobility.


Hyaluronan, NMR spectroscopy, mass spectrometry, polysaccharide, glycosaminoglycan, cross-linking, hydrogel

Published in

Acta Universitatis Agriculturae Sueciae
2019, number: 2019:30
ISBN: 978-91-7760-378-8, eISBN: 978-91-7760-379-5
Publisher: Department of Molecular Sciences, Swedish University of Agricultural Sciences

    UKÄ Subject classification

    Polymer Chemistry
    Organic Chemistry
    Analytical Chemistry

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