Photothermal‐enhanced in situ supramolecular hydrogel promotes bacteria‐infected wound healing in diabetes

Abstract Bacterial infection can impede the healing of chronic wounds, particularly diabetic wounds. The high‐sugar environment of diabetic wounds creates a favorable condition for bacterial growth, posing a challenge to wound healing. In clinical treatment, the irregular shape of the wound and the poor mechanical properties of traditional gel adjuvants make them susceptible to mechanical shear and compression, leading to morphological changes and fractures, and difficult to adapt to irregular wounds. Traditional gel adjuvants are prepared in advance, while in situ gel is formed at the site of administration after drug delivery in a liquid state, which can better fit the shape of the wound. Therefore, this study developed an in situ HA/GCA/Fe2+‐GOx gel using a photothermal‐enhanced Fenton reaction to promote the generation of hydroxyl radicals (·OH). The generation of ·OH has an antibacterial effect while promoting the formation of the gel, achieving a dual effect. The addition of double‐bonded adamantane (Ada) interacts with the host‐guest effect of graphene oxide and the double‐bond polymerization of HAMA gel, making the entire gel system more complete. At the same time, the storage modulus (G′) of the gel increased from 130 to 330 Pa, enhancing the mechanical properties of the gel. This enables the gel to have better injectability and self‐healing effects. The addition of GOx can consume glucose at the wound site, providing a good microenvironment for the repair of diabetic wounds. The gel has good biocompatibility and in a diabetic rat wound model infected with S. aureus, it can effectively kill bacteria at the wound site and promote wound repair. Meanwhile, the inflammation of wounds treated with HA/GCA/Fe2+‐GOx + NIR was lighter compared to untreated wounds. Therefore, this study provides a promising strategy for treating bacterial‐infected diabetic wounds.

was kept constant, GOx = 10 μg/mL, and glucose = 1 mg/mL, and its absorption peak at 650 nm was measured to calculate the approximate amount of H2O2 produced by the reaction of the gel system.

Figure S1 .
Figure S1.FTIR spectrogram of GO-CD.Where the black arrows indicate the characteristic peaks of GO: the peaks around 1721 cm -1 indicate the generation of stretching vibrations of COOH in GO; the peaks around 1578 cm -1 indicate the generation of stretching vibrations of COO-in GO.The green boxes indicate the characteristic peaks of β-CD: around 600-900 cm -1 indicates the characteristic peaks of bending vibration of the sugar ring; the wider characteristic peaks at 3200-3400 cm -1 are the stretching vibration of OH in the sugar ring.The blue arrow around 2850 cm -1 indicates the characteristic peak of C-H generated by the covalent bonding of GO with β-CD.

Figure S3 .
Figure S3.Quantitative detection of H2O2 production from the HA/GCA/Fe 2+ -GOx gel system.(A) The FeSO4 concentration was kept constant (100 μM) and reacted with different concentrations of H2O2, the colour change was observed by TMB detection and the UV absorbance was measured.(B) The absorbance value at 650 nm was taken, and linear analysis was done.(C) The concentration of FeSO4 (100 μM, 20-fold dilution over the final sample)

Figure S4 .
Figure S4.The production of •OH was determined under different experimental conditions using TA (5 mM) as a fluorescent indicator.where the concentration of H2O2 was 100 μM and FeSO4 was 20 μM.

Figure S6 .
Figure S6.(A) GOx standard curve.(B) Glucose content of the solution before (left) and after (right) GOx treatment.(C)H2O2 standard curve.(D) H2O2 content of the solution before (left) and after (right) GOx treatment.

Figure S12 .
Figure S12.Bacterial plates of wound sites 24 h after treatment in different subgroups.