A comprehensive rheological study on the influence of ion charge density and valence in ionotropically crosslinked alginate hydrogels for bioprinting

Author(s)

Fernandes, Paula Cristina Gomes ; Filgueiras, Viviane Fajardo ; Matte, Bibiana Franzen ; Lopes, Joao Henrique

• Document type: Journal article
• Source: International Journal of Biological Macromolecules; v. 316, p. 13-pg., 2025-06-01.

Abstract

Alginate hydrogels are extensively utilized as a foundation for bioink formulations due to their facile gelation properties. In this study, the rheological behavior of alginate cross-linked by various biologically relevant ions was systematically investigated, with an emphasis on bioink development for bioprinting applications. While the cross-linking of alginate by calcium (Ca2+) ions is well-established, this work explored the effects of other divalent alkaline earth ions, including magnesium (Mg2+), strontium (Sr2+), and barium (Ba2+), as well as trivalent ions iron (Fe3+) and lanthanum (La3+), and the monovalent ion cesium (Cs+). Rotational and oscillatory rheological tests were performed to assess the gelation behavior and mechanical properties of the hydrogels. The findings demonstrated that alginate gelation is influenced not only by ion valency but also by charge density. Among the divalent ions, Mg2+ failed to cross-link alginate chains effectively, whereas Ba2+ produced hydrogels with superior rheological properties. The trivalent ions, Fe3+ and La3+, induced gelation at relatively low concentrations, highlighting the role of charge density in enhancing cross-linking efficiency. In contrast, the monovalent ion Cs+, with its low charge density, did not promote hydrogel formation. These results were critically analyzed in the context of bioprinting requirements, emphasizing the importance of ion selection for tailoring bioink properties to meet the mechanical and structural demands of bioprinting processes. (AU)

• FAPESP's process: 22/03247-6 - Investigation of mesoporous nanoparticles from bioactive glasses containing niobium in bone tissue engineering
• Grantee: João Henrique Lopes
• Support Opportunities: Research Grants - Initial Project
• FAPESP's process: 22/11767-0 - Research of alginate hydrogels cross-linking strategies for 3D bioprinting
• Grantee: Viviane Fajardo Filgueiras
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/07967-3 - Development of hybrid bioinks for 3D bioprinting applied to bone tissue engineering
• Grantee: Paula Cristina Gomes Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 23/07910-4 - Multi-user Equipment approved in grant 2022/03247-6: Fourier-Transform Infrared Spectroscopy (FTIR)
• Grantee: João Henrique Lopes
• Support Opportunities: Multi-user Equipment Program