 Corresponding author: Reny I’tishom Department of Biomedical Science, Faculty of Medicine, Unviersitas Airlangga, Surabaya. Copyright © 2022 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Nano-Oxy: Diabetic ulcer treatment using oxygen nanoparticles concept as innovation in reducing amputation rates and antibiotics usage Shofiuddin Al Mufid 1 , Naufal Achmad Tsany Daffa 1 , Dedy Firmansyah 1 , Octaviana Galuh Pratiwi 1 , Innas Safira Putri 1 and Reny I’tishom 2, * 1 Medical Study Program, Faculty of Medicine, Universitas Airlangga, Surabaya. 2 Department of Biomedical Science, Faculty of Medicine, Unviersitas Airlangga, Surabaya. World Journal of Advanced Research and Reviews, 2022, 13(01), 309–316 Publication history: Received on 07 December 2021; revised on 09 January 2022; accepted on 11 January 2022 Article DOI: https://doi.org/10.30574/wjarr.2022.13.1.0031 Abstract Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia caused by defects in insulin secretion, insulin reactions, or both. More than one third of diabetic patients have complications in the form of diabetic ulcers, and half are infected, and 15% of these infections require limb amputation. High cost expenditure and risks of microbial resistance to antibiotics also adds the complexity of the problem. The purpose of this literature review is to offer Nano-Oxy, using oxygen in nanoparticle size, as an alternative diabetic ulcer treatment. Literature searching was conducted through online search method. Oxygen therapy has been widely used to treat diabetic ulcers, including hyperbaric oxygen therapy (HOT) and topical oxygen therapy (TOT). Both of them have good results on diabetic ulcer therapy. Oxygen can act as an antimicrobial agent through the activation mechanism of neutrophils and macrophages which play a role in phagocytosis process and ROS regeneration. Nano-Oxy has advantages than the previous therapy, such as it does not cause barotrauma, oxygen poisoning, and low risk of burning. The mechanism of how Nano-Oxy works is similar with the Micro-nanobubbles (MNBs) concept. The negatively charged surface of MNBs can prevent them from aggregating, attracts particles, and help remove debris. MNBs also generate free radicals while shrinking in water, which contribute to its antibacterial effect. In addition, Nano-oxygen technology can be applied externally, but still have effect on the intended target cells. Therefore, Nano-oxygen can be used as a diabetic ulcer therapy to replace the role of antibiotics. Keywords: Diabetic Ulcer; Bacteria Resistant; Diabetes Mellitus; Nano Oxygen; Oxygen Therapy 1. Introduction Diabetes mellitus is one of metabolic diseases characterized by chronic hyperglycemia caused by defects in insulin secretion, insulin reactions, or both [1]. The number of people with diabetes is expected to increase rapidly from 425 million in 2017 to a predicted value of 600 million in 2030. More than a third of people with diabetes have complications in the form of diabetic ulcers during their lifetime, half are infected, and 15% of these infections require limb amputation to prevent the development of infection [2]. The longer a person has diabetes mellitus, the greater the chance of suffering from chronic hyperglycemia which will eventually cause complications in the form of retinopathy, nephropathy, CHD, and diabetic ulcers [3].