Nanohybrid Double Network Hydrogels Based on a Platinum Nanozyme Composite for Antimicrobial and Diabetic Wound Healing

Abstract

Along with hypoxia, severe bacterial infection, and abnormal pH, continuous inflammatory response hinders diabetic wounds from healing. It leads to the accumulation of large amounts of reactive oxygen species (ROS) and therefore prevents the transition of diabetic wounds from the inflammatory phase to the proliferative phase. In this work, a nanohybrid double network hydrogel with injectable, self-healing, and tissue adhesion properties based on a platinum nanozyme composite (PFOB@PLGA@Pt) was constructed to manage diabetic wound healing. PFOB@PLGA@Pt exhibited oxygen supply capacity and enzyme catalytic performance accompanied by pH self-regulation in the entire phases of wound healing. In the first stage, the oxygen carried by perfluorooctyl bromide (PFOB) can ameliorate the hypoxia and boost the glucose oxidase-like catalyzed reaction of Pt NPs, leading to a lowered pH environment with gluconic acid. As a result, the NADH oxidaselike, peroxidase-like, and oxidase-like multiple enzyme activities were activated successively, leading to synergistic antibacterial effects through the production of ROS. After the bacterial infection had cleared, the catalase-like and superoxide dismutase-like activities of Pt NPs reshaped the redox microenvironment by scavenging the excess ROS, which transitioned the wound from the inflammatory phase to the proliferative phase. The microenvironmentally adaptive hydrogel treatment can cover all phases of wound healing, showing the significant promoting effect in the repair of diabetic infected wounds.

pH-Responsive Wound Dressing Based on Biodegradable CuP Nanozymes for Treating Infected and Diabetic Wounds

“…During this period, bacteria in the wound site tend to secrete significant amounts of lactic acid and carbonic acid, rendering the wound's pH slightly acidic. 24,65 As time progresses, diabetic wounds transition into a state of persistent chronic inflammatory response, leading to the accumulation of pro-inflammatory alkaline cytokines within the wound area, resulting in an alkaline shift in the wound microenvironment. 65 Notably, the Alg/CuP hydrogel designed in this study exhibits versatility in addressing skin wounds within complex pH environments.…”

“…Among these, some nanozymes even showcase pH-adjustable enzymatic activity. , In acidic environments, these nanozymes exhibit a predisposition toward peroxidase (POD) or oxidase (OXD) enzymatic activities, whereas under alkaline conditions, they tend to manifest superoxide dismutase (SOD) or catalase (CAT) enzymatic activities. , Numerous studies have suggested that this distinctive property equips these nanozymes with the capacity to exert therapeutic effects in various contexts. For instance, they can induce POD or OXD enzymatic activity to combat tumors or bacteria (pH < 7), , or stimulate SOD or CAT enzymatic activity in areas affected by tissue damage, thereby fostering tissue regeneration (pH > 7). , Considering that the microenvironment of chronic wounds, like diabetic wounds, is usually alkaline, and that the acidic metabolites produced by bacterial infection can decrease the pH of the wound, or even make it acidic, these pH-responsive nanozymes have the potential to dynamically adapt to the pathological microenvironment of chronic wounds, thereby optimally regulating and utilizing excess ROS. Nonetheless, in actual wound repair, regulation of endogenous ROS alone by nanozyme is often insufficient, especially when dealing with chronic refractory wounds possessing a complex wound microenvironment.…”

“…For instance, they can induce POD or OXD enzymatic activity to combat tumors or bacteria (pH < 7), 21,22 or stimulate SOD or CAT enzymatic activity in areas affected by tissue damage, thereby fostering tissue regeneration (pH > 7). 23,24 Considering that the microenvironment of chronic wounds, like diabetic wounds, is usually alkaline, and that the acidic metabolites produced by bacterial infection can decrease the pH of the wound, or even make it acidic, these pH-responsive nanozymes have the potential to dynamically adapt to the pathological microenvironment of chronic wounds, thereby optimally regulating and utilizing excess ROS. Nonetheless, in actual wound repair, regulation of endogenous ROS alone by nanozyme is often insufficient, especially when dealing with chronic refractory wounds possessing a complex wound microenvironment.…”

Recent progress in nanozymes for the treatment of diabetic wounds

“…Zhou et al firstly combined perfluorooctyl bromide (PFOB) and Pt NPs to form a nanozyme composite (PFOB@PLGA@Pt), and then PFOB@PLGA@Pt nanozyme and oxidized dextran (ODex) were introduced into methacrylate-anhydride gelatin (GelMA) hydrogel through a Schiff base bond to form PFOB@PLGA@Pt/gelMA/ODex hydrogel. 104 The hydrogel initially utilized PFOB-loaded oxygen to promote the GOx-like activity of Pt NPs to catalyze glucose to produce gluconic acid, thereby activating the POD-like activity of the hydrogel and producing ROS to destroy bacteria. Later in the healing process, the SOD- and CAT-like activities of Pt nanozymes were activated to remove excess ROS from the wound, thereby shortening the inflammatory period and accelerating wound healing.…”

Self-Assembled Nanoflowers Realizes Synergistic Sterilization with Photothermal and Chemical Kinetics Therapy

“…ROS production/elimination can be modulated according to the different pathologic microenvironments of implant infections at different stages of treatment, leading to adaptive tuning of antibiofilm activity and immune responses. Platinum nanoclusters have been widely reported for their excellent catalytic properties and good size for in vivo applications. − Yang et al precisely prepared platinum-based nanoenzymes by tuning the size of platinum through atomic layer deposition and explored size-dependent electronic and kinetic effects in peroxidase reactions and antimicrobial processes . Furthermore, Sharma synthesized a Pt/Au bimetallic nanoparticle and investigated its antibacterial properties .…”