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...

Full description

Bibliographic Details
Main Authors: Luis Andrés Pérez, Rebeca Hernández, José María Alonso, Raúl Pérez-González, Virginia Sáez-Martínez
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Polymers
Subjects:
Online Access:https://www.mdpi.com/2073-4360/15/4/966
_version_ 1797618527280037888
author Luis Andrés Pérez
Rebeca Hernández
José María Alonso
Raúl Pérez-González
Virginia Sáez-Martínez
author_facet Luis Andrés Pérez
Rebeca Hernández
José María Alonso
Raúl Pérez-González
Virginia Sáez-Martínez
author_sort Luis Andrés Pérez
collection DOAJ
description 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.
first_indexed 2024-03-11T08:13:59Z
format Article
id doaj.art-97bbd3dbc5c2430fa1cae1952d878f4a
institution Directory Open Access Journal
issn 2073-4360
language English
last_indexed 2024-03-11T08:13:59Z
publishDate 2023-02-01
publisher MDPI AG
record_format Article
series Polymers
spelling doaj.art-97bbd3dbc5c2430fa1cae1952d878f4a2023-11-16T22:52:20ZengMDPI AGPolymers2073-43602023-02-0115496610.3390/polym15040966Granular Disulfide-Crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability ParametersLuis Andrés Pérez0Rebeca Hernández1José María Alonso2Raúl Pérez-González3Virginia Sáez-Martínez4Instituto de Ciencia y Tecnología de Polímeros (ICTP-CSIC), c/Juan de la Cierva, 3, 28006 Madrid, SpainInstituto de Ciencia y Tecnología de Polímeros (ICTP-CSIC), c/Juan de la Cierva, 3, 28006 Madrid, Spaini+Med S. Coop. Parque Tecnológico de Álava, Albert Einstein 15, Nave 15, 01510 Vitoria-Gasteiz, Spaini+Med S. Coop. Parque Tecnológico de Álava, Albert Einstein 15, Nave 15, 01510 Vitoria-Gasteiz, Spaini+Med S. Coop. Parque Tecnológico de Álava, Albert Einstein 15, Nave 15, 01510 Vitoria-Gasteiz, SpainGranular 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.https://www.mdpi.com/2073-4360/15/4/966injectable hydrogelhyaluronic acidthiolmicrogelsgranular hydrogels
spellingShingle Luis Andrés Pérez
Rebeca Hernández
José María Alonso
Raúl Pérez-González
Virginia Sáez-Martínez
Granular Disulfide-Crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability Parameters
Polymers
injectable hydrogel
hyaluronic acid
thiol
microgels
granular hydrogels
title Granular Disulfide-Crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability Parameters
title_full Granular Disulfide-Crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability Parameters
title_fullStr Granular Disulfide-Crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability Parameters
title_full_unstemmed Granular Disulfide-Crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability Parameters
title_short Granular Disulfide-Crosslinked Hyaluronic Hydrogels: A Systematic Study of Reaction Conditions on Thiol Substitution and Injectability Parameters
title_sort granular disulfide crosslinked hyaluronic hydrogels a systematic study of reaction conditions on thiol substitution and injectability parameters
topic injectable hydrogel
hyaluronic acid
thiol
microgels
granular hydrogels
url https://www.mdpi.com/2073-4360/15/4/966
work_keys_str_mv AT luisandresperez granulardisulfidecrosslinkedhyaluronichydrogelsasystematicstudyofreactionconditionsonthiolsubstitutionandinjectabilityparameters
AT rebecahernandez granulardisulfidecrosslinkedhyaluronichydrogelsasystematicstudyofreactionconditionsonthiolsubstitutionandinjectabilityparameters
AT josemariaalonso granulardisulfidecrosslinkedhyaluronichydrogelsasystematicstudyofreactionconditionsonthiolsubstitutionandinjectabilityparameters
AT raulperezgonzalez granulardisulfidecrosslinkedhyaluronichydrogelsasystematicstudyofreactionconditionsonthiolsubstitutionandinjectabilityparameters
AT virginiasaezmartinez granulardisulfidecrosslinkedhyaluronichydrogelsasystematicstudyofreactionconditionsonthiolsubstitutionandinjectabilityparameters