Healing Diabetic Ulcers with MoO_3−X Nanodots Possessing Intrinsic ROS‐Scavenging and Bacteria‐Killing Capacities

Abstract

neutrophils in the ulcer area can produce excessive reactive oxygen species (ROS) which on one hand injury the epithelial cells to impede the wound recovery, and on the other hand block the supply of oxygen and nutrition to the ulcer area to hinder the angiogenesis. [2] In addition, the high level ROS can induce excessive inflammatory response of the macrophages, enhancing the wound vulnerability that further delays the recovery of DUs. [3] Moreover, the long-term open ulcers are more susceptible to pathogen infection, partly due to high local glucose level. [4] The infectious microorganisms can not only enhance the inflammatory response, interfere with the angiogenesis and epithelial proliferation, but also boost the generation of ROS in the ulcer areas. [5] The vicious circle of "excessive ROS-blocking the wound healingpromoting pathogenic infection-activating the generation of ROS" leads to the deterioration of DUs. In the absence of prompt and effective treatments, DUs may eventually deteriorate into lower limb amputation, giving rise to great physical and psychological trauma to the diabetic patients. [6] Thus, it is imperative to explore effective therapy for treating the early stage DUs to improve the life quality of the patients. [7] Diabetic ulcers (DUs) appearing as chronic wounds are difficult to heal due to the oxidative stress in the wound microenvironment and their high susceptibility to bacterial infection. A routine treatment combining surgical debridement with anti-infection therapy is widely used for treating DUs in the clinic, but hardly offers a satisfying wound healing outcome. It is known that a longterm antibiotic treatment may also lead to the drug resistance of pathogens. To address these challenges, new strategies combining both reactive oxygen species (ROS) scavenging and bacterial sterilization have been proposed for fighting against DUs. Following this idea, oxygen deficient molybdenum-based nanodots (MoO 3−X ) for healing the DUs are reported. The ROS scavenging ability of MoO 3−X nanodots is investigated and the antibacterial property of the nanodots is also demonstrated. The systematic cell and animal experimental results indicate that the MoO 3−X nanodots can effectively reduce inflammation, promote epithelial cell regeneration, accelerate angiogenesis, and facilitate DUs recovery. Most importantly, they present excellent capacity to diminish infection of methicillin-resistant Staphylococcus aureus, manifesting the potent application prospect of MoO 3−X nanodots for diabetic wound therapy.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smll.202107137.

Construction of multifunctional wound dressings with their application in chronic wound treatment

“…And in diabetic chronic wounds, high levels of glycation end products (AGEs) and an abnormal immune system may induce immune cells such as neutrophils to produce excess ROS (including superoxide anion, hydrogen peroxide, hydroxyl radicals, etc. ), 37 resulting in irreversible cell damage and poor angiogenesis. 23,38 Therefore, the feature to control inflammation is very important for wound dressings, and the strategies to suppress the long-term inflammatory response at the wound site are effective in improving the healing rate of chronic wounds.…”

Stimuli-responsive therapeutic systems for the treatment of diabetic infected wounds

“…3A). 62 Electron paramagnetic resonance spectral assay indicated that MoO 3−X could scavenge superoxide anions ( • O 2− ), hydroxyl radicals ( • OH), and hydrogen peroxide (H 2 O 2 ). Plate count results indicated that MoO 3−X could inactivate Gram-negative and Gram-positive pathogens, for example, Escherichia coli and Staphylococcus aureus.…”

An Optimally Designed Engineering Exosome–Reductive COF Integrated Nanoagent for Synergistically Enhanced Diabetic Fester Wound Healing

“…[2] During traditional monotherapy, inflammation response, bacterial colonization, and microvascular dysfunction often result in the deceleration and even failure of chronic wound healing. [3][4][5] Besides, the occurrence of undesirable side effects and the appearance of drug-resistant bacteria are also depleting the existent drug library. Considering the complicated etiological factors of the injured tissue microenvironment, combination of two or more medicines with nontoxicities and different therapeutic functions are critical steps for successful management of chronic wound regeneration.…”