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

[EN] 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.
This researchwas funded by Deutsche Forschungsgemeinschaft (DFG) grant CI 203/1-2, DFG Emmy Noether grant (CI 203/2-1) and the Berlin-Brandenburg School for Regenerative Therapies (BSRT) Extension grant. This work was also supported by an EPSRC Program Grant (EP/P001114/1) and from the UK Regenerative Medicine Platform "Acellular/Smart Materials-3D Architecture" (MR/R015651/1). This research was also supported by the Spanish State Research Agency (AEI) through the PID2019-106000RB-C21/AEI/10.13039/501100011033 project (including the FEDER funds). The article processing charge was funded by the Max Planck Society.