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

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.

Engineering Hydrogels for Affinity-Based Release of Therapeutic Proteins

“…For example, Trujillo et al synthesized norbornene-modified alginate hydrogels crosslinked with thiolated protease-degradable peptides using UVinitiated thiol−ene polymerization and incorporated maleimide-functionalized PEGylated fibronectin through thiol− maleimide click chemistry (Figure 1B). 45 Proteins that naturally contain a free cysteine or are modified with one on the C-terminus can take advantage of maleimide-functionalized hydrogel polymers for conjugation via thiol−Michael addition. This strategy is advantageous for immobilizing protein or peptide binders specifically onto maleimide-functionalized polymers.…”

Nanocellulose-based hydrogels for drug delivery

“…Ionic crosslinking, also known as ionic bond polymerization, refers to organic polymer crosslinking by ionic bonds. 64 The physically crosslinked hydrogel formed by the bonding of the polyelectrolyte and multivalent ions with opposite charges is also called an ionic crosslinked hydrogel. 65 Mild reaction conditions, good performance at room temperature and no organic solvents are the advantages of ionic crosslinked nanocellulose-based hydrogels.…”

Tissue engineering modalities in skeletal muscles: focus on angiogenesis and immunomodulation properties

“…In vitro analysis revealed the formation of multinucleated myocytes by encapsulating C2C12 myoblasts within self-healing PEG hydrogel [ 117 ]. The culture of ECs within the self-healing and glucose-sensitive poly(PEG-diacrylate-dithiothreitol (PEGDA/DTT) hydrogel with hollow tubular form activated certain genes such as CD31, eNOS, and VEGFR after 3 days in culture medium [ 118 ]. ECs cultured within the unique tubular structure mimic the native vessel-like niche after 14 days.…”