Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications

Hydrogels based on natural polysaccharides can have unique properties and be tailored for several applications, which may be mainly limited by the fragile structure and weak mechanical properties of this type of system. We successfully prepared cryogels made of newly synthesized kefiran exopolysacch...

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Main Authors: Hajer Radhouani, Cristiana Gonçalves, F. Raquel Maia, Eduarda P. Oliveira, Rui L. Reis, Joaquim M. Oliveira
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/6/1662
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author Hajer Radhouani
Cristiana Gonçalves
F. Raquel Maia
Eduarda P. Oliveira
Rui L. Reis
Joaquim M. Oliveira
author_facet Hajer Radhouani
Cristiana Gonçalves
F. Raquel Maia
Eduarda P. Oliveira
Rui L. Reis
Joaquim M. Oliveira
author_sort Hajer Radhouani
collection DOAJ
description Hydrogels based on natural polysaccharides can have unique properties and be tailored for several applications, which may be mainly limited by the fragile structure and weak mechanical properties of this type of system. We successfully prepared cryogels made of newly synthesized kefiran exopolysaccharide-chondroitin sulfate (CS) conjugate via carbodiimide-mediated coupling to overcome these drawbacks. The freeze-thawing procedure of cryogel preparation followed by lyophilization is a promising route to fabricate polymer-based scaffolds with countless and valuable biomedical applications. The novel graft macromolecular compound (kefiran-CS conjugate) was characterized through <sup>1</sup>H-NMR and FTIR spectroscopy—which confirmed the structure of the conjugate, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)—which mirrored good thermal stability (degradation temperature of about 215 °C) and, finally, gel permeation chromatography–size exclusion chromatography (GPC-SEC)—which proved an increased molecular weight due to chemical coupling of kefiran with CS. At the same time, the corresponding cryogels physically crosslinked after the freeze-thawing procedure were investigated by scanning electron microscopy (SEM), Micro-CT, and dynamic rheology. The results revealed a prevalent contribution of elastic/storage component to the viscoelastic behavior of cryogels in swollen state, a micromorphology with micrometer-sized open pores fully interconnected, and high porosity (ca. 90%) observed for freeze-dried cryogels. Furthermore, the metabolic activity and proliferation of human adipose stem cells (hASCs), when cultured onto the developed kefiran-CS cryogel, was maintained at a satisfactory level over 72 h. Based on the results obtained, it can be inferred that the newly freeze-dried kefiran-CS cryogels possess a host of unique properties that render them highly suitable for use in tissue engineering, regenerative medicine, drug delivery, and other biomedical applications where robust mechanical properties and biocompatibility are crucial.
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spelling doaj.art-edc88c7faf1e46f680da5141b8fd79762023-11-18T12:04:41ZengMDPI AGPharmaceutics1999-49232023-06-01156166210.3390/pharmaceutics15061662Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical ApplicationsHajer Radhouani0Cristiana Gonçalves1F. Raquel Maia2Eduarda P. Oliveira3Rui L. Reis4Joaquim M. Oliveira53B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, PortugalHydrogels based on natural polysaccharides can have unique properties and be tailored for several applications, which may be mainly limited by the fragile structure and weak mechanical properties of this type of system. We successfully prepared cryogels made of newly synthesized kefiran exopolysaccharide-chondroitin sulfate (CS) conjugate via carbodiimide-mediated coupling to overcome these drawbacks. The freeze-thawing procedure of cryogel preparation followed by lyophilization is a promising route to fabricate polymer-based scaffolds with countless and valuable biomedical applications. The novel graft macromolecular compound (kefiran-CS conjugate) was characterized through <sup>1</sup>H-NMR and FTIR spectroscopy—which confirmed the structure of the conjugate, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)—which mirrored good thermal stability (degradation temperature of about 215 °C) and, finally, gel permeation chromatography–size exclusion chromatography (GPC-SEC)—which proved an increased molecular weight due to chemical coupling of kefiran with CS. At the same time, the corresponding cryogels physically crosslinked after the freeze-thawing procedure were investigated by scanning electron microscopy (SEM), Micro-CT, and dynamic rheology. The results revealed a prevalent contribution of elastic/storage component to the viscoelastic behavior of cryogels in swollen state, a micromorphology with micrometer-sized open pores fully interconnected, and high porosity (ca. 90%) observed for freeze-dried cryogels. Furthermore, the metabolic activity and proliferation of human adipose stem cells (hASCs), when cultured onto the developed kefiran-CS cryogel, was maintained at a satisfactory level over 72 h. Based on the results obtained, it can be inferred that the newly freeze-dried kefiran-CS cryogels possess a host of unique properties that render them highly suitable for use in tissue engineering, regenerative medicine, drug delivery, and other biomedical applications where robust mechanical properties and biocompatibility are crucial.https://www.mdpi.com/1999-4923/15/6/1662biomedical devicecarbodiimide-mediated couplingcharacterizationchondroitin sulfatecryogelation techniquekefiran
spellingShingle Hajer Radhouani
Cristiana Gonçalves
F. Raquel Maia
Eduarda P. Oliveira
Rui L. Reis
Joaquim M. Oliveira
Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications
Pharmaceutics
biomedical device
carbodiimide-mediated coupling
characterization
chondroitin sulfate
cryogelation technique
kefiran
title Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications
title_full Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications
title_fullStr Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications
title_full_unstemmed Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications
title_short Development of Conjugated Kefiran-Chondroitin Sulphate Cryogels with Enhanced Properties for Biomedical Applications
title_sort development of conjugated kefiran chondroitin sulphate cryogels with enhanced properties for biomedical applications
topic biomedical device
carbodiimide-mediated coupling
characterization
chondroitin sulfate
cryogelation technique
kefiran
url https://www.mdpi.com/1999-4923/15/6/1662
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