Hypoxia,
excessive reactive oxygen species (ROS), impaired angiogenesis,
lasting inflammation, and bacterial infection, are key problems impeding
diabetic wound healing. Particularly, controllable oxygen release
and ROS scavenging capacities are critical during the wound healing
process. Here, an injectable hydrogel based on hyaluronic acid-graft-dopamine (HA-DA) and polydopamine (PDA) coated Ti3C2 MXene nanosheets is developed catalytically
cross-linked by an oxyhemoglobin/hydrogen (HbO2/H2O2) system combined with mild photothermal stimulation
for diabetic wound healing. HbO2 not only acts as a horseradish
peroxidase-like to catalyze the hydrogel formation but also as an
oxygen carrier to controllably release oxygen when activated by the
mild heat produced from near-infrared (NIR) irradiation. Specifically,
HbO2 can provide oxygen repeatedly by binding oxygen in
the air when the NIR is off. The stable photoresponsive heating behavior
of MXene ensures the repeatable oxygen release. Additionally, artificial
nonenzymatic antioxidant MXene nanosheets are proposed to scavenge
excessive reactive nitrogen species and ROS including H2O2, O2
•–, and •OH, keeping the intracellular redox homeostasis and
alleviating oxidative stress, and eradicate bacteria to avoid infection.
The antioxidant and antibacterial abilities of MXene are further improved
by PDA coating, which also promotes the MXene nanosheets cross-linking
into the network of the hydrogel. HA-DA molecules endow the hydrogel
with the capacity to regulate macrophage polarization from M1 to M2
to achieve anti-inflammation. More importantly, the MXene-anchored
hydrogel with multifunctions including tissue adhesion, self-healing,
injectability, and hemostasis, combined with mild photothermal stimulation,
greatly promotes human umbilical vein endothelial cell proliferation
and migration and notably facilitates infected diabetic wound healing.
Bacterial infection, tissue hypoxia and inflammatory response can hinder the infected wound repair process. To mitigate the above issues, tannic acid-chelated Fe-decorated molybdenum disulfide nanosheets (MoS
2
@TA/Fe NSs) with dual enzyme activities were developed and anchored to a multifunctional hydrogel. The hydrogel exhibited excellent antibacterial ability owing to the combined effects of photothermal therapy (PTT), glutathione (GSH) loss, and the peroxidase (POD)-like activity (catalyse H
2
O
2
into ·OH under acid condition) of MoS
2
@TA/Fe NSs. Benefitting from the catalase (CAT)-like activity, the hydrogel could decompose H
2
O
2
into O
2
at neutral pH to relieve hypoxia and supply adequate O
2
. POD-like activity was mainly attributed to MoS
2
NSs, while CAT-like activity was primarily due to TA/Fe complex. Moreover, MoS
2
@TA/Fe NSs endowed the hydrogel with outstanding anti-oxidant ability to scavenge redundant reactive oxygen species (ROS) and reactive nitrogen species (RNS) under neutral environment to maintain the balance of antioxidant systems and prevent inflammation. In addition, the hydrogel could inhibit the release of inflammatory factors for the anti-inflammatory property of TA. TA retained partial phenolic hydroxyl groups, which cross-linked the nanosheets to the network structure of the hydrogel and promoted the adhesion of hydrogels. Due to the dynamic boron ester bonds between polyvinyl alcohol (PVA), dextran (Dex), MoS
2
@TA/Fe, and borax, the hydrogel demonstrated fast self-healing and rapid shape adaptability. This shape-adaptable adhesive hydrogel could fill the whole wound and closely contact the wound, ensuring that it achieved its functions with maximum efficiency. The MoS
2
@TA/Fe nanozyme-anchored multifunctional hydrogel showed high potential for bacteria-infected wound healing.
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