Radio frequency gradient enhanced diffusion-edited semi-solid state NMR spectroscopy for detailed structural characterization of chemically modified hyaluronic acid hydrogels

Abstract Applications of functionalized hyaluronic acid (HA) hydrogels for numerous biomedical applications requires their detailed structural characterization. Since these materials are prepared by multistep chemical modifications in the solid phase and not amenable to characterization by standard...

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Main Authors: Peyman Sakhaii, Bojan Bohorc, Thomas Olpp, Mandy Mohnicke, Joerg Rieke-Zapp, Pradeep K. Dhal
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-78731-6
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author Peyman Sakhaii
Bojan Bohorc
Thomas Olpp
Mandy Mohnicke
Joerg Rieke-Zapp
Pradeep K. Dhal
author_facet Peyman Sakhaii
Bojan Bohorc
Thomas Olpp
Mandy Mohnicke
Joerg Rieke-Zapp
Pradeep K. Dhal
author_sort Peyman Sakhaii
collection DOAJ
description Abstract Applications of functionalized hyaluronic acid (HA) hydrogels for numerous biomedical applications requires their detailed structural characterization. Since these materials are prepared by multistep chemical modifications in the solid phase and not amenable to characterization by standard analytical tools, we employed high-resolution solid-state NMR spectroscopy to gain detailed insights into the structures of the functionalized HA hydrogels. Divinyl sulfone crosslinked HA hydrogels were converted into maleimide-functionalized hydrogels, which were subjected to chemoselective thiol-maleimide reaction using L-cysteine as the protein mimetic thiol reagent. To overcome challenges associated with obtaining high-resolution NMR spectra of crosslinked hydrogels (such as line broadening and overlapping of signals of the hydrogel with those of residual reagents and solvents used during multi-step reaction processes on insoluble polymer matrices), we devised a radio frequency mediated diffusion-edited semi solid-state NMR technique. This technique enabled us to record NMR spectra of hydrogels exclusively by effectively suppressing signals associated with low molecular weight impurities. Thus, it became possible to perform in-depth characterization of these chemically modified HA hydrogels including quantification of reaction outcome for each reaction step.
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spelling doaj-art-cab79d88f0fb4c2f8996cc695e9333d52025-08-20T02:22:20ZengNature PortfolioScientific Reports2045-23222024-11-0114111210.1038/s41598-024-78731-6Radio frequency gradient enhanced diffusion-edited semi-solid state NMR spectroscopy for detailed structural characterization of chemically modified hyaluronic acid hydrogelsPeyman Sakhaii0Bojan Bohorc1Thomas Olpp2Mandy Mohnicke3Joerg Rieke-Zapp4Pradeep K. Dhal5Global CMC Development, Global R&D, Sanofi, Industrial Park HoechstGlobal CMC Development, Global R&D, Sanofi, Industrial Park HoechstGlobal CMC Development, Global R&D, Sanofi, Industrial Park HoechstGlobal CMC Development, Global R&D, Sanofi, Industrial Park HoechstManufacturing Science and Analytical Technology, Sanofi, Industrial Park HoechstGlobal CMC Development, Global R&D, SanofiAbstract Applications of functionalized hyaluronic acid (HA) hydrogels for numerous biomedical applications requires their detailed structural characterization. Since these materials are prepared by multistep chemical modifications in the solid phase and not amenable to characterization by standard analytical tools, we employed high-resolution solid-state NMR spectroscopy to gain detailed insights into the structures of the functionalized HA hydrogels. Divinyl sulfone crosslinked HA hydrogels were converted into maleimide-functionalized hydrogels, which were subjected to chemoselective thiol-maleimide reaction using L-cysteine as the protein mimetic thiol reagent. To overcome challenges associated with obtaining high-resolution NMR spectra of crosslinked hydrogels (such as line broadening and overlapping of signals of the hydrogel with those of residual reagents and solvents used during multi-step reaction processes on insoluble polymer matrices), we devised a radio frequency mediated diffusion-edited semi solid-state NMR technique. This technique enabled us to record NMR spectra of hydrogels exclusively by effectively suppressing signals associated with low molecular weight impurities. Thus, it became possible to perform in-depth characterization of these chemically modified HA hydrogels including quantification of reaction outcome for each reaction step.https://doi.org/10.1038/s41598-024-78731-6
spellingShingle Peyman Sakhaii
Bojan Bohorc
Thomas Olpp
Mandy Mohnicke
Joerg Rieke-Zapp
Pradeep K. Dhal
Radio frequency gradient enhanced diffusion-edited semi-solid state NMR spectroscopy for detailed structural characterization of chemically modified hyaluronic acid hydrogels
Scientific Reports
title Radio frequency gradient enhanced diffusion-edited semi-solid state NMR spectroscopy for detailed structural characterization of chemically modified hyaluronic acid hydrogels
title_full Radio frequency gradient enhanced diffusion-edited semi-solid state NMR spectroscopy for detailed structural characterization of chemically modified hyaluronic acid hydrogels
title_fullStr Radio frequency gradient enhanced diffusion-edited semi-solid state NMR spectroscopy for detailed structural characterization of chemically modified hyaluronic acid hydrogels
title_full_unstemmed Radio frequency gradient enhanced diffusion-edited semi-solid state NMR spectroscopy for detailed structural characterization of chemically modified hyaluronic acid hydrogels
title_short Radio frequency gradient enhanced diffusion-edited semi-solid state NMR spectroscopy for detailed structural characterization of chemically modified hyaluronic acid hydrogels
title_sort radio frequency gradient enhanced diffusion edited semi solid state nmr spectroscopy for detailed structural characterization of chemically modified hyaluronic acid hydrogels
url https://doi.org/10.1038/s41598-024-78731-6
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AT thomasolpp radiofrequencygradientenhanceddiffusioneditedsemisolidstatenmrspectroscopyfordetailedstructuralcharacterizationofchemicallymodifiedhyaluronicacidhydrogels
AT mandymohnicke radiofrequencygradientenhanceddiffusioneditedsemisolidstatenmrspectroscopyfordetailedstructuralcharacterizationofchemicallymodifiedhyaluronicacidhydrogels
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