Tailoring supramolecular guest-host hydrogel viscoelasticity with covalent fibrinogen double networks

Supramolecular chemistry has enabled the design of tunable biomaterials that mimic the dynamic and viscoelastic characteristics of the extracellular matrix. However, the noncovalent nature of supramolecular bonds renders them inherently weak, limiting their applicability to many biomedical applications. To address this, we formulated double network (DN) hydrogels through a combination of supramolecular and covalent networks to tailor hydrogel viscoelastic properties. Specifically, DN hydrogels were formed through the combination of supramolecular guest-host (GH) hyaluronic acid (HA) networks with covalent networks from the photocrosslinking of acrylated poly(ethylene glycol) modified fibrinogen (PEG-fibrinogen) and PEG diacrylate. DN hydrogels exhibited higher compressive moduli, increased failure stresses, and increased toughness when compared to purely covalent networks. While GH concentration had little influence on the compressive moduli across DN hydrogels, an increase in the GH concentration resulted in more viscous behavior of DN hydrogels. High viability of encapsulated bovine mesenchymal stromal cells (MSCs) was observed across groups with enhanced spreading and proliferation in DN hydrogels with increased GH concentration. This combination of supramolecular and covalent chemistries enables the formation of dynamic hydrogels with tunable properties that can be customized towards repair of viscoelastic tissues.