Cited by 35Hydrogels: synthesis, properties, applicationsPolysaccharides Composition and ApplicationsCellular Mechanics and Interactions

Dynamic Mechanical Control of Alginate-Fibronectin Hydrogels with Dual Crosslinking: Covalent and Ionic

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Trujillo, Sara, Seow, Melanie, Lueckgen, Aline, Salmeron-Sanchez, Manuel, Cipitria, Amaia·2021·Polymers

Abstract

Alginate is a polysaccharide used extensively in biomedical applications due to its biocompatibility and suitability for hydrogel fabrication using mild reaction chemistries. Though alginate has commonly been crosslinked using divalent cations, covalent crosslinking chemistries have also been developed. Hydrogels with tuneable mechanical properties are required for many biomedical applications to mimic the stiffness of different tissues. Here, we present a strategy to engineer alginate hydrogels with tuneable mechanical properties by covalent crosslinking of a norbornene-modified alginate using ultraviolet (UV)-initiated thiol-ene chemistry. We also demonstrate that the system can be functionalised with cues such as full-length fibronectin and protease-degradable sequences. Finally, we take advantage of alginate’s ability to be crosslinked covalently and ionically to design dual crosslinked constructs enabling dynamic control of mechanical properties, with gels that undergo cycles of stiffening–softening by adding and quenching calcium cations. Overall, we present a versatile hydrogel with tuneable and dynamic mechanical properties, and incorporate cell-interactive features such as cell-mediated protease-induced degradability and full-length proteins, which may find applications in a variety of biomedical contexts.

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  • Dual crosslinking approaches that combine ionic and covalent crosslinking can provide additional mechanical strength and controlled degradation, ensuring the barrier remains effective during critical phases of tissue healing.

    “Furthermore, dual crosslinking approaches that combine ionic and covalent crosslinking can provide additional mechanical strength and controlled degradation, ensuring that the barrier remains effective during the critical phases of tissue healing [190].”

    From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [190]

    Results §3.3 reports that adding ionic crosslinking to covalently crosslinked alginate hydrogels significantly increased their stiffness. Results §3.1 and the Discussion describe protease-degradable crosslinkers and on-demand degradation, but the paper does not establish that dual crosslinking controls degradation or keeps a barrier effective during tissue healing. No page numbers are available in our copy. (LLM, conf=0.88)

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Authors
Trujillo, S., Seow, M., Lueckgen, A., Salmeron-Sanchez, M., & Cipitria, A.
Affiliations
  • Centro de Biomateriales e Ingeniería Tisular (ES)
  • Charité – Universitätsmedizin Berlin (DE)
  • Centre for the Cellular Microenvironment, University of Glasgow, 72-76 Oakfield Avenue, Glasgow G12 8LT, UK
  • Max Planck Institute of Colloids and Interfaces (DE)
Corresponding author
Cipitria, Amaia
Venue
Polymers
Publisher
MDPI AG
Published
2021-01-29
Volume
13
Issue
3
Pages
433
ISSN
2073-4360 (ISSN-L)
OpenAlex
W3127538136
Cited by
35
References
3
Citations by year
2026: 8 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 1
FWCI
1.39
Type
journal article
Language
en
Open access
Locations
  • Polymers (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • RiuNet (Universitat Politècnica de València) (submittedVersion, cc-by-nc-nd)
Funders
  • Deutsche Forschungsgemeinschaft (CI 203/1-2, CI 203/2-1)
  • Engineering and Physical Sciences Research Council (EP/P001114/1)
  • Berlin-Brandenburg School for Regenerative Therapies (BSRT) Extension grant (N.A.)
  • UK Regenerative Medicine Platform “Acellular / Smart Materials – 3D Architecture” (MR/R015651/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Polysaccharides Composition and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
alginate hydrogel, fibronectin, dual crosslinking, covalent cross-linking, ionic crosslinking, calcium cations, thiol-ene click chemistry, tunable mechanical properties, dynamic stiffness

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