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

Abstract

Nanozymes, emerging nanomaterials for wound healing, exhibit enzyme-like activity to modulate the levels of reactive oxygen species (ROS) at wound sites. Yet, the solo regulation of endogenous ROS by nanozymes often falls short, particularly in chronic refractory wounds with complex and variable pathological microenvironments. In this study, we report the development of a multifunctional wound dressing integrating a conventional alginate (Alg) hydrogel with a newly developed biodegradable copper hydrogen phosphate (CuP) nanozyme, which possesses good near-infrared (NIR) photothermal conversion capabilities, sustained Cu ion release ability, and pH-responsive peroxidase/catalase-mimetic catalytic activity. When examining acute infected wounds characterized by a low pH environment, the engineered Alg/ CuP composite hydrogels demonstrated high bacterial eradication efficacy against both planktonic bacteria and biofilms, attributed to the combined action of catalytically generated hydroxyl radicals and the sustained release of Cu ions. In contrast, when applied to chronic diabetic wounds, which typically have a high pH environment, these composite hydrogels exhibit significant angiogenic performance. This is driven by the provision of catalytically generated dissolved oxygen and a beneficial supplement of Cu ions released from the degradable CuP nanozyme. Further, a mild thermal effect induced by NIR irradiation amplifies the catalytic activities and bioactivity of Cu ions, thereby enhancing the healing process of both infected and diabetic wounds. Our study validates that the synergistic integration of photothermal effects, catalytic activity, and released Cu ions can concurrently yield high antibacterial efficiency and tissue regenerative activity, rendering it highly promising for various clinical applications in wound healing.

Nanozymes for the Therapeutic Treatment of Diabetic Foot Ulcers

“…The different optimal pH ranges hinder the crosstalk of multiple enzyme activities. Feng et al developed a novel pH-responsive composite hydrogel (Alg/CuP) based on copper nanozyme for DFU in an alkaline environment. Alg/CuP dressing exhibited CAT-like activity, where abundant O 2 derived from hydrogen peroxide conversion and continuous release of copper ions promoted angiogenesis and accelerated wound repair.…”

Schiff Base-Based Hydrogel Embedded with In Situ Generated Silver Nanoparticles Capped by a Hyaluronic Acid–Diethylenetriamine Derivative for Wound Healing Application

“…In the acute infected wounds, pH is acidic during inflammation, transitioning to a more basic range during granulation and then becoming acidic again during re-epithelialization. A recent study has shown that infected wounds shift from a slightly acidic environment to increased acidification after 24 h due to metabolite production from bacterial proliferation . In contrast, chronic wounds tends to be alkaline, even if acidic metabolites produced by bacterial infection can lower the wound’s pH or render it acidic. , Considering this context, it is conceivable that a pH-responsive hydrogel capable of releasing antimicrobial agents in response to microenvironmental acidification could be applied during the acute phase of an infected wound.…”