Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survival

Tissue defects can lead to serious health problems and often require grafts or transplants to repair damaged soft tissues. However, these procedures can be complex and may not always be feasible due to a lack of available tissue. Hydrogels have shown potential as a replacement for tissue grafts due...

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Main Authors: Maria Merino-Gómez, Maria Godoy-Gallardo, Mathias Wendner, Miguel A. Mateos-Timoneda, F. Javier Gil, Roman A. Perez
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2023.1147943/full
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author Maria Merino-Gómez
Maria Godoy-Gallardo
Mathias Wendner
Miguel A. Mateos-Timoneda
F. Javier Gil
F. Javier Gil
Roman A. Perez
author_facet Maria Merino-Gómez
Maria Godoy-Gallardo
Mathias Wendner
Miguel A. Mateos-Timoneda
F. Javier Gil
F. Javier Gil
Roman A. Perez
author_sort Maria Merino-Gómez
collection DOAJ
description Tissue defects can lead to serious health problems and often require grafts or transplants to repair damaged soft tissues. However, these procedures can be complex and may not always be feasible due to a lack of available tissue. Hydrogels have shown potential as a replacement for tissue grafts due to their ability to support cell survival and encapsulate biomolecules such as growth factors. In particular, guanosine-based hydrogels have been explored as a potential solution, but they often exhibit limited stability which hampers their use in the biofabrication of complex grafts. To address this issue, we explored the use of borate ester chemistry and more complex boric acid derivatives to improve the stability and properties of guanosine-based hydrogels. We hypothesized that the aromatic rings in these derivatives would enhance the stability and printability of the hydrogels through added π-π stack interactions. After optimization, 13 compositions containing either 2-naphthylboronic acid or boric acid were selected. Morphology studies shows a well-defined nanofibrilar structure with good printable properties (thixotropic behaviour, print fidelity and printability). Moreover, the pH of all tested hydrogels was within the range suitable for cell viability (7.4–8.3). Nevertheless, only the boric acid-based formulations were stable for at least 7 days. Thus, our results clearly demonstrated that the presence of additional aromatic rings did actually impair the hydrogel properties. We speculate that this is due to steric hindrance caused by adjacent groups, which disrupt the correct orientation of the aromatic groups required for effective π-π stack interactions of the guanosine building block. Despite this drawback, the developed guanosine-boric acid hydrogel exhibited good thixotropic properties and was able to support cell survival, proliferation, and migration. For instance, SaOS-2 cells planted on these printed structures readily migrated into the hydrogel and showed nearly 100% cell viability after 7 days. In conclusion, our findings highlight the potential of guanosine-boric acid hydrogels as tissue engineering scaffolds that can be readily enhanced with living cells and bioactive molecules. Thus, our work represents a significant advancement towards the development of functionalized guanosine-based hydrogels.
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spelling doaj.art-0dcacc3ad5e54a20b8abda73404317622023-03-20T05:51:01ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-03-011110.3389/fbioe.2023.11479431147943Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survivalMaria Merino-Gómez0Maria Godoy-Gallardo1Mathias Wendner2Miguel A. Mateos-Timoneda3F. Javier Gil4F. Javier Gil5Roman A. Perez6Bioengineering Institute of Technology (BIT), Faculty of Medicine and Health Sciences, International University of Catalonia (UIC), Sant Cugat del Vallès, SpainBioengineering Institute of Technology (BIT), Faculty of Medicine and Health Sciences, International University of Catalonia (UIC), Sant Cugat del Vallès, SpainBioengineering Institute of Technology (BIT), Faculty of Medicine and Health Sciences, International University of Catalonia (UIC), Sant Cugat del Vallès, SpainBioengineering Institute of Technology (BIT), Faculty of Medicine and Health Sciences, International University of Catalonia (UIC), Sant Cugat del Vallès, SpainBioengineering Institute of Technology (BIT), Faculty of Medicine and Health Sciences, International University of Catalonia (UIC), Sant Cugat del Vallès, SpainDepartment of Dentistry, Faculty of Dentistry, International University of Catalonia (UIC), Sant Cugat del Vallès, SpainBioengineering Institute of Technology (BIT), Faculty of Medicine and Health Sciences, International University of Catalonia (UIC), Sant Cugat del Vallès, SpainTissue defects can lead to serious health problems and often require grafts or transplants to repair damaged soft tissues. However, these procedures can be complex and may not always be feasible due to a lack of available tissue. Hydrogels have shown potential as a replacement for tissue grafts due to their ability to support cell survival and encapsulate biomolecules such as growth factors. In particular, guanosine-based hydrogels have been explored as a potential solution, but they often exhibit limited stability which hampers their use in the biofabrication of complex grafts. To address this issue, we explored the use of borate ester chemistry and more complex boric acid derivatives to improve the stability and properties of guanosine-based hydrogels. We hypothesized that the aromatic rings in these derivatives would enhance the stability and printability of the hydrogels through added π-π stack interactions. After optimization, 13 compositions containing either 2-naphthylboronic acid or boric acid were selected. Morphology studies shows a well-defined nanofibrilar structure with good printable properties (thixotropic behaviour, print fidelity and printability). Moreover, the pH of all tested hydrogels was within the range suitable for cell viability (7.4–8.3). Nevertheless, only the boric acid-based formulations were stable for at least 7 days. Thus, our results clearly demonstrated that the presence of additional aromatic rings did actually impair the hydrogel properties. We speculate that this is due to steric hindrance caused by adjacent groups, which disrupt the correct orientation of the aromatic groups required for effective π-π stack interactions of the guanosine building block. Despite this drawback, the developed guanosine-boric acid hydrogel exhibited good thixotropic properties and was able to support cell survival, proliferation, and migration. For instance, SaOS-2 cells planted on these printed structures readily migrated into the hydrogel and showed nearly 100% cell viability after 7 days. In conclusion, our findings highlight the potential of guanosine-boric acid hydrogels as tissue engineering scaffolds that can be readily enhanced with living cells and bioactive molecules. Thus, our work represents a significant advancement towards the development of functionalized guanosine-based hydrogels.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1147943/fullguanosine-based hydrogelsboric acid derivativesnucleoside3D printingprintable hydrogels
spellingShingle Maria Merino-Gómez
Maria Godoy-Gallardo
Mathias Wendner
Miguel A. Mateos-Timoneda
F. Javier Gil
F. Javier Gil
Roman A. Perez
Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survival
Frontiers in Bioengineering and Biotechnology
guanosine-based hydrogels
boric acid derivatives
nucleoside
3D printing
printable hydrogels
title Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survival
title_full Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survival
title_fullStr Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survival
title_full_unstemmed Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survival
title_short Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survival
title_sort optimization of guanosine based hydrogels with boric acid derivatives for enhanced long term stability and cell survival
topic guanosine-based hydrogels
boric acid derivatives
nucleoside
3D printing
printable hydrogels
url https://www.frontiersin.org/articles/10.3389/fbioe.2023.1147943/full
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