Granular Disulfide-Crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability Parameters

Granular polymer hydrogels based on dynamic covalent bonds are attracting a great deal of interest for the design of injectable biomaterials. Such materials generally exhibit shear-thinning behavior and properties of self-healing/recovery after the extrusion that can be modulated through the interac...

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Bibliographic Details
Published in:Polymers 2023-02, Vol.15 (4), p.966
Main Authors: Pérez, Luis Andrés, Hernández, Rebeca, Alonso, José María, Pérez-González, Raúl, Sáez-Martínez, Virginia
Format: Article
Language:English
Subjects:
Autoclaving
Biocompatibility
Biological products
Biomedical materials
Chemical bonds
Chemical reactions
Covalent bonds
Disulfides
Ethylenediaminetetraacetic acid
Extrusion
Filaments
Fragmentation
Hyaluronic acid
Hydrogels
Injectability
Microgels
Microparticles
Molecular weight
NMR
Nuclear magnetic resonance
Oxidizing agents
Physiological aspects
Physiology
Rheological properties
Rheology
Shear thinning (liquids)
Substitution reactions
Thiols
Tissue engineering
Toxicity
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Summary:Granular polymer hydrogels based on dynamic covalent bonds are attracting a great deal of interest for the design of injectable biomaterials. Such materials generally exhibit shear-thinning behavior and properties of self-healing/recovery after the extrusion that can be modulated through the interactions between gel microparticles. Herein, bulk macro-hydrogels based on thiolated-hyaluronic acid were produced by disulphide bond formation using oxygen as oxidant at physiological conditions and gelation kinetics were monitored. Three different thiol substitution degrees (SD%: 65%, 30% and 10%) were selected for hydrogel formation and fully characterized as to their stability in physiological medium and morphology. Then, extrusion fragmentation technique was applied to obtain hyaluronic acid microgels with dynamic disulphide bonds that were subsequently sterilized by autoclaving. The resulting granular hyaluronic hydrogels were able to form stable filaments when extruded through a syringe. Rheological characterization and cytotoxicity tests allowed to assess the potential of these materials as injectable biomaterials. The application of extrusion fragmentation for the formation of granular hyaluronic hydrogels and the understanding of the relation between the autoclaving processes and the resulting particle size and rheological properties should expand the development of injectable materials for biomedical applications.
ISSN:2073-4360
2073-4360
DOI:10.3390/polym15040966