Viscoelastic hydrogels
are gaining interest as they possess necessary
requirements for bioprinting and injectability. By means of reversible,
dynamic covalent bonds, it is possible to achieve features that recapitulate
the dynamic character of the extracellular matrix. Dually cross-linked
and double-network (DN) hydrogels seem to be ideal for the design
of novel biomaterials and bioinks, as a wide range of properties required
for mimicking advanced and complex tissues can be achieved. In this
study, we investigated the fabrication of chondroitin sulfate/hyaluronic
acid (CS/HA)-based DN hydrogels, in which two networks are interpenetrated
and cross-linked with the dynamic covalent bonds of very different
lifetimes. Namely, Diels–Alder adducts (between methylfuran
and maleimide) and hydrazone bonds (between aldehyde and hydrazide)
were chosen as cross-links, leading to viscoelastic hydrogels. Furthermore,
we show that viscoelasticity and the dynamic character of the resulting
hydrogels could be tuned by changing the composition, that is, the
ratio between the two types of cross-links. Also, due to a very dynamic
nature and short lifetime of hydrazone cross-links (∼800 s),
the DN hydrogel is easily processable (e.g., injectable) in the first
stages of gelation, allowing the material to be used in extrusion-based
3D printing. The more long-lasting and robust Diels–Alder cross-links
are responsible for giving the network enhanced mechanical strength
and structural stability. Being highly charged and hydrophilic, the
cross-linked CS and HA enable a high swelling capacity (maximum swelling
ratio ranging from 6 to 12), which upon confinement results in osmotically
stiffened constructs, able to mimic the mechanical properties of cartilage
tissue, with the equilibrium moduli ranging from 0.3 to 0.5 MPa. Moreover,
the mesenchymal stromal cells were viable in the presence of the hydrogels,
and the effect of the degradation products on the macrophages suggests
their safe use for further translational applications. The DN hydrogels
with dynamic covalent cross-links hold great potential for the development
of novel smart and tunable viscoelastic materials to be used as biomaterial
inks or bioinks in bioprinting and regenerative medicine.