Authors; Year	Type of Study	Patients	Conclusion
Morteza Izadi. et al. 2019 [14].	Single-blind randomized clinical trial	200 patients: 100 patients treated with ozone, usual conservative treatment, 100 patients treated with routine care.	Objective: to be able to identify the efficacy and safety of ozone in ulcers of patients with diabetic foot. Conclusion: ozone therapy reduces healing time, allows better healing, reduces C-reactive protein and sedimentation rate, and decreases the amputation rate.
Kasmawati Kadir. et al. 2020 [17].	Non-randomized controlled study	27 patients: 14 treated with standard care, bandage, oxygen-ozone therapy, 13 treated with bandage, standard care.	Objective: to identify the effectiveness of the combination of ozone therapy and standard wound treatment in order to reduce bacterial colonies and stimulate wound healing. Conclusion: the combination of ozone therapy at 70 μg/mL and the standard care performed significantly reduces the number of bacteria in wounds, but no significant changes in healing are shown.
Qing Wen. et al. 2021 [22].	Systematic review	12 articles were obtained, with a total of 1055 participants in total.	Objective: To evaluate the efficacy and safety of ozone therapy in chronic ulcers. Conclusion: ozone reduces the wound area and decreases the amputation rate in patients with diabetic foot ulcers, but this is not evident in completely healed ulcers.
Suchin Dhamnaskar. et al. 2021 [7].	Observational prospective comparative study of cohorts	162 patients: 81 of them were treated with debridement, cleaning, Betadine, and bandage; the other 81 were treated with the previous treatment together with topical ozone.	Objective: to assess the safety and efficacy of topical ozone gas used in diabetic foot ulcers. Conclusion: during an acceleration in the change in exudate, ozone allowed a more rapid creation of granulation tissue, promoted the disappearance of inflammation, reduced microbial colonization, and improved healing of the wound edges. In addition, hospital stay was significantly reduced.
Tássia Lima Bomfim. et al. 2021 [20].	Systematic review	44 articles were obtained at the beginning, and after a selection, the final result was 7 articles.	Objective: to summarize the different evidence on the therapeutic use of ozone in people with venous ulcers to promote decision-making on the use of this treatment, improve wound healing, and enhance patient safety. Conclusion: they support the effectiveness of this therapy as an additional treatment for ulcers, it reduces the rate of amputation, infection, and hospitalization, but more studies are needed to prove its efficacy in healing ulcers effectively and safely.
Jing Zhang. Et al. 2014 [8].	Randomized controlled prospective clinical study.	50 patients: 25 patients were treated with non-invasive ozone and oxygen treatment together with standard treatment, and the other 25 patients were treated only with standard treatment.	Objective: to observe the effects of ozone therapy on the healing of diabetic foot ulcers and the expressions of vascular endothelial growth factor (VEGF), transforming growth factor (TGF), and platelet-derived growth factors (PDGF) of these after treatment. Conclusion: ozone and oxygen treatment significantly promoted wound healing, and an increase in VEGF, TGF, and PDGF expressions was observed in the ozone group. The effectiveness of this treatment in healing, according to these results, may be due to the increase in endogenous growth factors.
Erin Fitzpatrick. et al. 2018 [16].	Systematic review	In the first search, 12 articles were obtained. After the exclusion criteria, 9 articles were obtained.	Objective: to investigate the possibility of ozone therapy as an effective medical procedure for use in chronic wounds. Conclusion: ozone therapy has positive effects on chronic ulcers, but it is necessary to carry out more research to agree on a specific application method to obtain the most appropriate dose for its effectiveness.
Xiaoxiao Hu. et al. 2019 [10].	Prospective study	136 patients: 68 patients were treated with VAC + ozone water wash, and 68 patients treated with VAC.	Objective: to find out the efficacy of treatment with vacuum negative pressure and washing with ozone water for diabetic foot ulcers. Conclusion: the use of these two drugs in combination produces an improvement in the recovery of ulcers and reduces the duration of treatment and pain during it.
Jarosław Pasek. et al. 2022 [9].	Prospective study	54 patients were treated with local ozone therapy: 25 male patients and 29 female patients.	Objective: to examine the efficacy of local ozone therapy in venous ulcers, taking into account the area of the wound and its pain. Conclusion: the application of local ozone therapy reduces the surface of the wound and the intensity of the pain perceived by the patient.
Urban Machado. et al., 2022 [19].	Systematic review	30 trials: 12 trials were withdrawn as they did not meet the inclusion criteria. 18 articles were used to conduct this review.	Objective: to assess clinical trials of the last 10 years on the safety and effectiveness of ozone therapy used in dermatological conditions. Conclusion: ozone therapy is effective, and it could be used as an alternative or complementary treatment in dermatological conditions such as diabetic foot ulcers, but more research should be carried out on its risk–benefit ratio.
Aparecida Oliveira. et al. 2020 [21].	Systematic review	326 articles: after the exclusion criteria, the final result was 17 articles.	Objective: to determine the safety and efficacy of ozone therapy in various dermatological conditions. Conclusion: in the short term, ozone therapy is effective, especially in ulcers and scars, but more research is still necessary to observe in the long term what are the adverse effects that it can present.
Svitlana Y. Karatieva. et al. 2021 [23].	Prospective study	122 patients participated: 50 patients were treated with ozone together with surgical and general treatment, and 72 patients were treated with surgical treatment.	Objective: to favor the evolution of purulent wounds in diabetes using ozone therapy. Conclusion: it was possible to observe that ozone did not have a negative impact on homeostasis and the level of intoxication of the body; in addition, they observed a positive effect on the evolution of the wound in purulent processes.
Navid Faraji. et al. 2021 [18].	Case report	A 52-year-old patient suffered a traumatic injury to the right tibia due to a fall from a bicycle.	Objective: to study the effectiveness of ozone therapy in the wound of a specific patient. Conclusion: ozone therapy, together with the silver dressing, improves healing, presents antibacterial effects, prevents the appearance of infections, and has a positive effect on glucose and its metabolism.
Gheuca˘ Solovâstru. et al. 2015 [11].	Randomized controlled trial	29 patients: 15 patients treated with ozonated oil + a-bisabolol + standard care, and 14 patients treated with standard care + epithelization cream.	Objective: to evaluate the efficacy of an ozonated oil aerosol combined with a-bisabolol in chronic venous ulcers, comparing it with the standard epithelization cream. Conclusion: in this study, it was observed that the ozone in this formula increases its antiseptic, oxygenating, and immunological properties; in addition, a-bisabolol has anti-inflammatory and calming properties, so this formulation offers a promising therapeutic option in the treatment of venous ulcers.
Yi-Ting Zhou. et al. 2016 [12].	Randomized clinical trial	92 patients participated: 50 were treated with ozone gas bath + endovenous laser therapy and 42 of them with endovenous laser therapy.	Objective: to demonstrate the effectiveness of the ozone gas bath combined with endovenous laser therapy for the treatment of venous ulcers present in the lower limbs. Conclusion: laser therapy, together with an ozone gas bath, is effective and safe for venous ulcers present in lower limbs; it can be used as an alternative to long-term compression therapy or surgery.
Faisal Amir. et al. 2022 [13].	Simple random sampling.	26 patients participated: 13 were treated with bag ozone therapy, and another 13 were treated with standard treatment.	Objective: to investigate the effect of the use of ozone bag therapy in the healing of diabetic foot ulcers. Conclusion: in this study, they observed differences in wound healing in patients with diabetic ulcers, healing better in patients treated with ozone.
Myroslav V. Rosul. et al. 2016 [15].	Randomized clinical trial.	47 patients participated, divided into two groups. Group B was treated with traditional therapy, while group A was treated with traditional therapy and systemic ozone therapy, administered for 12–14 days.	Objective: to demonstrate the effectiveness of ozone in complex therapies in patients with diabetic foot. Conclusion: they demonstrated that ozone has a positive effect on the course of the wound process, improving regenerative processes, peroxidation indexes, and the antioxidant system and reducing hospital stays.