The
development of natural polymer-based hydrogels, combining outstanding
injectability, self-healing, and tissue adhesion, with mechanical
performance, able to facilitate full-thickness skin wound healing,
remains challenging. We have developed an injectable micellar hydrogel
(AF127/HA-ADH/OHA-Dop) with outstanding adhesive and self-healing
properties able to accelerate full-thickness skin wound healing. Dopamine-functionalized
oxidized hyaluronic acid (OHA-Dop), adipic acid dihydrazide-modified
HA (HA-ADH), and aldehyde-terminated Pluronic F127 (AF127) were employed
as polymer backbones. They were cross-linked in situ using Schiff base dynamic covalent bonds (AF127 micelle/HA-ADH network
and HA-ADH/OHA-Dop network), hydrogen bonding, and π–π
stacking interactions. The resulting multicross-linked double-network
design forms a micellar hydrogel. The unique multicross-linked double-network
structure endows the hydrogel with both improved injection abilities
and mechanical performance while self-healing faster than single-network
hydrogels. Inspired by mussel foot adhesive protein, OHA-Dop mimics
the catechol groups seen in mussel proteins, endowing hydrogels with
robust adhesion properties. We also demonstrate the potential of our
hydrogels to accelerate full-thickness cutaneous wound closure and
improve skin regeneration with reduced scarring. We anticipate that
our hydrogel platform based on a novel multicross-linked double-network
design will transform the future development of multifunctional wound
dressings.
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