Dynamic G-quadruplex
supramolecular hydrogels have aroused great
interest in a broad range of bioapplications. However, neither the
development of native extracellular matrix (ECM)-derived natural biopolymer-functionalized
G-quadruplex hydrogels nor their use to create perfusable self-supporting
hydrogels has been explored to date, despite their intrinsic potential
as carrier vehicles of therapeutic agents, or even living cells in
advanced regenerative therapies, or as platforms to enable the diffusion
of nutrients and oxygen to sustain long-term cell survival. Herein,
we developed a dynamic co-assembling multicomponent system that integrates
guanosine (G), 3-aminophenylboronic acid functionalized hyaluronic
acid (HA-PBA), and potassium chloride to bioengineer strong, homogeneous,
and transparent HA-functionalized G-quadruplex hydrogels with injectable,
thermo-reversible, conductive, and self-healing properties. The supramolecular
polymeric hydrogels were developed by hydrogen bonding andπ–πstacking interactions between G coupledviadynamic covalent boronate ester bonds to HA-PBA and
stabilized by K+ions, as demonstrated by a combination
of experiments and molecular dynamics simulations. The intrinsic instability
of the self-assembled G-quadruplex structures was used to bioengineer
self-supporting perfusable multicomponent hydrogels with interconnected
size and shape-tunable hollow microchannels when embedded in 3D methacrylated
gelatin supporting matrices. The microchannel-embedded 3D constructs
have shown enhanced cell viability when compared to the bulk hydrogels,
holding great promise for being use as artificial vessels for enabling
the diffusion of nutrients and oxygen essential for cell survival.
The proposed approach opens new avenues on the use of ECM-derived
natural biopolymer-functionalized dynamic G-quadruplex hydrogels to
design next-generation smart systems for being used in tissue regeneration,
drug screening, or organ-on-a-chip.