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Cited by 313D Printing in Biomedical ResearchHydrogels: synthesis, properties, applicationsTissue Engineering and Regenerative Medicine

Sr2+ vs. Ca2+ as post-processing ionic crosslinkers: Implications for 3D bioprinting of polysaccharide hydrogels in tissue engineering

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Vajda, Jernej, Vihar, Boštjan, Ćurić, Laura Činč, Maver, Uroš, Vesenjak, Matej, Dubrovski, Polona Dobnik, Milojević, Marko·2023·Journal of Materials Research and Technology
DOI 10.1016/j.jmrt.2023.01.149
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Abstract

Among the possible ionic crosslinkers Ca2+ is the most widely used. However, due to its numerous physiological functions, other cations such as Sr2+ may be more suitable depending on the application. Because a systematic comparison is currently lacking, this work aims to compare solutions of CaCl2 and SrCl2 as ionic crosslinkers of alginate- and cellulose-based materials and to investigate their effects on the structural and biological properties of 3D bioprinted scaffolds. In particular, swelling and degradation under cell culture conditions, mechanical properties (with quasi-static compression tests), surface topology (with scanning electron microscopy and atomic force microscopy) and elemental composition were investigated. In addition, cytotoxicity on pancreatic islet cells was assessed by measuring viability, metabolic activity and morphology. The obtained results show that Sr2+-crosslinked scaffolds have higher compressive strength, swell faster and degrade more slowly under cell culture conditions and have a rougher surface. Both crosslinking agents were gentle on the cells, either when directly embedded into scaffolds or in contact with scaffold extracts, and allowed stable culture for 30 days. However, Sr2+-crosslinked scaffolds elicited higher metabolic activity. Overall, Sr2+ are a viable crosslinking alternative to Ca2+ and allow expanding the range of scaffold properties by adjusting the concentration or ratio in a mixed solution.

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  • Incorporating multivalent ions such as Ba2+ or Sr2+ can enhance network stability, prolonging the material's functional lifespan.

    “incorporating multivalent ions such as Ba2+ or Sr2+ can enhance network stability, prolonging the material’s functional lifespan (Figure 9A) [187,188,189].”

    From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [187]

    The Results (§3.2.1) report that Sr2+-crosslinked scaffolds degraded more slowly than Ca2+-crosslinked scaffolds, and the Conclusions (§4) say Sr2+ is more suitable where long-term scaffold stability is needed. This supports the stability and lifespan point for Sr2+ in the hydrogels studied, but the paper does not establish it for Ba2+ or materials generally. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Ionic crosslinking with Ca2+ allows for rapid gelation and easy hydrogel formation.

    “While ionic crosslinking with Ca2+ allows for rapid gelation and easy hydrogel formation, incorporating multivalent ions such as Ba2+ or Sr2+ can enhance network stability, prolonging the material’s functional lifespan (Figure 9A) [187,188,189].”

    From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [187]

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Cited by

Sorted by citations

Authors
Vajda, J., Vihar, B., Ćurić, L. Č., Maver, U., Vesenjak, M., Dubrovski, P. D., & Milojević, M.
Affiliations
University of Maribor (SI)
Corresponding author
Milojević, Marko
ORCID
Venue
Journal of Materials Research and Technology
Publisher
Elsevier BV
Published
2023-03
Volume
23
Pages
1805-1820
ISSN
  • 2214-0697 (ISSN-L)
  • 2238-7854
DOI
10.1016/j.jmrt.2023.01.149
OpenAlex
W4318015009
Cited by
31
References
1
Citations by year
2026: 8 · 2025: 12 · 2024: 8 · 2023: 3
FWCI
2.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Materials Research and Technology (publishedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
Funders
Javna Agencija za Raziskovalno Dejavnost RS (I0-0029, L7-4494, P3-0036, Z3-4529)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
strontium ions, calcium ions, ionic crosslinking, polysaccharide hydrogels, alginate, cellulose, 3D bioprinting, tissue engineering scaffolds, compressive strength, swelling and degradation, surface roughness, cytotoxicity, pancreatic islet cells

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