Sulfonated hyaluronic acid-based polymers and hydrogels using thiol-ene and thiol-Michael reactions

DOI

Non-sulfated polysaccharides like hyaluronic acid (HA) have been widely studied as scaffold material for tissue engineering applications. To mimic the function of sulfated glycosaminoglycan in the matrix, sulfate groups can be grafted. However, here, harsh reaction conditions are required which induce significant backbone degradation. As an alternative, sulfonates (R-SO3-) have been shown to resemble the function of sulfates yet have not been introduced on polysaccharides. Using a two-step strategy, we introduced a tunable amount of sulfonate groups on HA, without requiring harsh reaction conditions and organic solvents. By varying the degree of carboxylic acid activation using 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), norbornene (NB, 3–18%) or maleimide (MAL, 2–14%) groups were grafted. Subsequently, 3-mercapto-1-propanesulfonate was coupled in high efficiency on the addressable groups via orthogonal thiol-ene and thiol-Michael addition. Additionally, we demonstrated the formation of hydrogels using poly(ethylene glycol)-di-SH as a crosslinker. However, because of the low crosslinking kinetics, HA-MAL appeared not useful for application. Simultaneous addition of the crosslinker and MPS to norbornyl-conjugated HA’s in various ratios enabled the formation of hydrogels with tunable stiffness and degree of sulfonate groups. The simple strategy is likely applicable to other commonly used polysaccharides and therefore interesting to the broader tissue engineering community.

Identifier
DOI https://doi.org/10.34894/JMPZUL
Metadata Access https://dataverse.nl/oai?verb=GetRecord&metadataPrefix=oai_datacite&identifier=doi:10.34894/JMPZUL
Provenance
Creator Beeren, Ivo ORCID logo; Dijkstra, Pieter ORCID logo; Albillos Sanchez, Ane (ORCID: 0009-0006-0596-402X); Ramis, Jopeth ORCID logo; Perin, Francesca ORCID logo; Mota, Carlos ORCID logo; Camarero-Espinosa, Sandra ORCID logo; Moroni, Lorenzo ORCID logo; Baker, Matthew ORCID logo
Publisher DataverseNL
Contributor Baker, Matthew; Hebels, Dennie; Dataverse Support Contact
Publication Year 2026
Rights CC-BY-4.0; info:eu-repo/semantics/openAccess; http://creativecommons.org/licenses/by/4.0
OpenAccess true
Contact Baker, Matthew (Maastricht University); Hebels, Dennie (Maastricht University); Dataverse Support Contact (Maastricht University)
Representation
Resource Type Dataset
Format application/zip
Size 229380758; 226571043; 950498; 7603879; 3566231
Version 1.0
Discipline Life Sciences; Medicine