Conventional wound dressings for infected diabetic wounds (IDWs) typically target only the wound surface, often neglecting the need for multifunctional therapies that address deeper tissue layers, resulting in less effective treatment outcomes. Emerging research suggests that a comprehensive approach to IDW therapy should involve the transdermal delivery of therapeutic agents capable of staged bacterial eradication, reactive oxygen species (ROS) scavenging, and angiogenesis. This study introduces a novel metal-phenolic nanozyme, CuTA@MnO 2 nanoflake, designed for transdermal delivery in IDW therapy. The nanozyme is synthesized by loading copper ions (Cu 2+ ) onto manganese dioxide (MnO 2 ) via in-situ polymerization, with tannic acid (TA) as a linker, and encapsulated in a hyaluronic acid (HA) solution to form a photothermally controlled microneedle system. In a IDW rat model, this system effectively delivered photothermal therapy, eliminating bacteria under 808 nm near-infrared light. The heat-induced HA degradation released the CuTA@MnO 2 nanoflake, where MnO 2 and TA reduced ROS levels, providing antioxidant effects. Concurrently, released Cu 2+ promoted angiogenesis, significantly accelerating wound healing. Whole transcriptome RNA sequencing confirmed that the CuTA@MnO 2 microneedle enhanced angiogenesis and collagen remodeling, along with reduced inflammation. The CuTA@MnO 2 microneedle offers a promising platform for the staged treatment of IDWs through bacterial eradication, oxidant scavenging, and angiogenesis promotion.
Periodontitis is a chronic inflammatory disease deriving from dental plaque, characterized by the excessive accumulation of reactive oxygen species (ROS), matrix metalloproteinase (MMP) and other substances, resulting in the destruction of periodontal tissues. At present, the main therapeutic modalities, such as local mechanical debridement and antibiotic delivery, are not only difficult to solve the intractable bacterial biofilm effectively but also tricky to ameliorate the excessive inflammatory response as well as regenerate the impaired periodontal tissues. Herein, we have proposed the TM/BHT/CuTA hydrogel system formed by the self-assembly of the copper-based nanozyme (copper tannic acid coordination nanosheets, CuTA NSs) and the triglycerol monostearate/2,6-di-tert-butyl-4-methylphenol (TM/BHT) hydrogel. The negatively charged TM/BHT/CuTA can retain at the inflammation sites with a positive charge through electrostatic adsorption and hydrolyze in response to the increasing MMP of periodontitis, realizing the on-demand release of the CuTA nanozyme. The released CuTA nanozyme has antibacterial and antiplaque properties. Meanwhile, as a metal-phenolic nanozyme, it can scavenge multiple ROS by simulating the cascade process of superoxide dismutase (SOD) and catalase (CAT). Further, the CuTA nanozyme can modulate the macrophage polarization from M1 phenotype to M2 phenotype through the Nrf2/NF-κB pathway, which reduces the pro-inflammatory cytokines, increases the anti-inflammatory cytokines, and promotes the expression of osteogenetic genes successively, thus relieving the inflammation and accelerating the tissue regeneration of periodontitis. Altogether, this multifunctional nanozyme on-demand release platform (TM/BHT/CuTA) provides a desirable strategy for the treatment of periodontitis.
危险品化学品经营许可证（带存储）