An Immunomodulatory Hydrogel by Hyperthermia‐Assisted Self‐Cascade Glucose Depletion and ROS Scavenging for Diabetic Foot Ulcer Wound Therapeutics

Abstract

Current therapeutic protocols for diabetic foot ulcers (DFUs), a severe and rapidly growing chronic complication in diabetic patients, remain nonspecific. Hyperglycemia‐caused inflammation and excessive reactive oxygen species (ROS) are common obstacles encountered in DFU wound healing, often leading to impaired recovery. These two effects reinforce each other, forming an endless loop. However, adequate and inclusive methods are still lacking to target these two aspects and break the vicious cycle. This study proposes a novel approach for treating DFU wounds, utilizing an immunomodulatory hydrogel to achieve self‐cascade glucose depletion and ROS scavenging to regulate the diabetic microenvironment. Specifically, AuPt@melanin‐incorporated (GHM3) hydrogel dressing is developed to facilitate efficient hyperthermia‐enhanced local glucose depletion and ROS scavenging. Mechanistically, in vitro/vivo experiments and RNA sequencing analysis demonstrate that GHM3 disrupts the ROS‐inflammation cascade cycle and downregulates the ratio of M1/M2 macrophages, consequently improving the therapeutic outcomes for dorsal skin and DFU wounds in diabetic rats. In conclusion, this proposed approach offers a facile, safe, and highly efficient treatment modality for DFUs.This article is protected by copyright. All rights reserved

Nanozymes for the Therapeutic Treatment of Diabetic Foot Ulcers

“…Thus, a comprehensive therapeutic strategy based on nanozymatic hydrogels simultaneously scavenging ROS, alleviating hypoxia, promoting neoangiogenesis, and modulating the immune system was realized. Liang et al 220 prepared AuPt@melaninbinding (GHM 3 ) hydrogel dressing via a one-step redox reaction approach designed to promote effective thermotherapy-enhanced local glucose consumption and ROS clearance. Melanin, a classical ROS scavenging material, can also be used for the deposition of Au NPs (GOx-like) and Pt NPs (CATlike) due to the abundant polyphenol groups on its surface.…”

Conjugated Network Supporting Highly Surface-Exposed Ru Site-Based Artificial Antioxidase for Efficiently Modulating Microenvironment and Alleviating Solar Dermatitis

“…To address the excess ROS and oxidative stress microenvironment, there are antioxidant substances and natural antioxidase systems in the living system, including catalase (CAT) and superoxide dismutase (SOD). − However, the direct usage of CAT and SOD suffer from intrinsic limitations such as poor stability, difficulty in storage, and challenges in mass production. − Nowadays, artificial enzymes with CAT-like and SOD-like properties are designed to modulate ROS and oxidative stress. − Among them, artificial nanobiocatalysts with diverse metal phthalocyanine coordination structures inspired by the coordination environments in CAT and SOD have attracted extensive attention . Compared with the unsatisfactory performance and low stability of small molecular metal phthalocyanine, macromolecular metal-coordinated polyphthalocyanine with a π-conjugated network structure has been expected to become next-generation nanobiocatalysts featuring a high delocalization effect of electrons, high density of metal active centers, and high physicochemical stability. − Our previous work has identified that Ru is a member of platinum group metals that shows ROS-scavenging catalytic activity. , However, underutilization of Ru active sites in the inner nanobiocatalysts limits the access to the reactants, which leads to hampered mass transport. , Importantly, it was shown that artificial nanobiocatalysts with efficient ROS-scavenging catalytic activity can be designed by further highly surface-exposed Ru active sites.…”

Injectable Dynamic ROS-Responsive COF-Modified Microalgae Gels for In Vivo bFGF Delivery to Treat Diabetic Wounds

“…Importantly, the design and synthesis of a multifunctional platform system to address ischemia and hypoxia, promote angiogenesis, and eliminate ROS is of great clinical significance for the efficient treatment of diabetic chronic wounds. 24,25 In this study, we developed a dynamic oxygen-releasing COF-modified microalgae gel for the combined treatment of chronic diabetic wounds. Notably, an amine-functionalized COF-1 has been reported by mixing 3-aminopropyl triethoxysilane (APTES) into established COF-1 recipe via Brønstedtype interactions.…”

“…Therefore, introducing COF for synergistic treatment to effectively remove ROS is a promising therapeutic strategy for the impaired healing of diabetic foot ulcers. Importantly, the design and synthesis of a multifunctional platform system to address ischemia and hypoxia, promote angiogenesis, and eliminate ROS is of great clinical significance for the efficient treatment of diabetic chronic wounds. , …”