NIR- and pH-responsive double-crosslinked inulin-tannic acid hydrogel with antioxidant and Anti-Staphylococcus aureus Activity.

Oxidative stress and bacterial infections can lead to compromised tissue regeneration in chronic wounds. Since traditional treatments are often ineffective, in this study a hydrogel based on two inulin derivatives, called dcINU-TA-NS, was design as multifunctional wound dressing platform with in vitro Anti-Staphylococcus aureus and antioxidant performance. Thanks to double crosslinking the hydrogel is characterized by modulable viscoelastic properties: dynamic interactions, based on the boronic ester bonds between inulin functionalized with 3-aminophenyl boronic acid (INU-APBA) and tannic acid (TA), ensure adaptability and adhesion to the injured site and ease of application; afterward a covalent crosslinking is obtained by UV cross-linking of the methacrylic groups of methacrylate inulin (INU-MA), giving greater persistence to the hydrogel at the site of interest. Thanks to the presence of TA, the hydrogel demonstrated a strong in vitro antioxidant activity, which lasts up to a week and is essential for reducing oxidative stress and promoting healing. Furthermore, the sensitivity of the boronic bonds to acidic pH allows for increased release of TA in an inflammatory environment. To ensure antibacterial efficacy, we introduced manganese dioxide nanosheets (NS), which exhibit photothermal activity upon NIR irradiation, making the polysaccharide platform thereby enabling antibacterial photothermal therapy (PTTA), which demonstrated in vitro activity exclusively against Staphylococcus aureus after a single irradiation. The photostability of the hydrogel allows for multiple irradiation cycles to increase effectiveness. Cytocompatibility was assessed on FD-MSC and RAW 264.7 cells.