Therapy For Diabetic Foot Ulcers Research Articles

Effect of aspirin on platelet-rich plasma of diabetes mellitus with lower extremity atherosclerosis.

Aim: Platelet-rich plasma (PRP), enriched with multiple growth factors, is a promising adjunctive therapy for diabetic foot ulcers (DFUs). As a classic anti-platelet drug for diabetic patients, the effects of aspirin on the content of growth factors in PRP remains unclear.Methods: Our study enrolled diabetic patients who were currently taking or not taking aspirin as the research subjects, with healthy volunteers as the control. PRP from these individuals was activated with glucose calcium and thrombin. Growth factors levels in PRP activated supernatant (PRP-AS) and wound healing ability of platelet gel (PG) in the full-thickness skin defect diabetic mouse model were compared.Results: We found the level of growth factors in PRP-AS derived from two groups of diabetic patients were not statistically different, whereas both lower than that from healthy volunteers. Similarly, we found better wound healing ability of PG from healthy volunteers than those from diabetic patients, but no difference between the two groups of diabetic patients in the mouse model.Discussion: Aspirin does not interfere with autologous PRP therapy when using calcium gluconate and thrombin as agonists. However considering the content of growth factors, PRP from healthy volunteers is a preferable option for promoting DFU repair.

Efficacy of 3D Wound Assessment in Predicting Granulation Tissue Velocity Following Negative Pressure Wound Therapy in Diabetic Foot Ulcers

Category: Diabetes; Midfoot/Forefoot Introduction/Purpose: Wound healing in diabetic foot ulcers (DFU) poses challenges, requiring extensive debridement and amputations. Negative pressure wound therapy (NPWT) can be utilized for DFUs with large soft tissue defects to promote granulation tissue growth. The optimal timeframe for successful NPWT lacks extensive studies. Advanced wound scanning with a three-dimensional (3D) camera can enhance DFU area and volume calculations. This study aimed to investigate the efficacy of 3D wound assessment in predicting granulation tissue filling velocity following NPWT in DFUs. Methods: After receiving IRB approval from the single Korean center, a retrospective case series study was performed for 101 DFUs (Wagner classification 3 and 4) undergoing NPWT from September 2018 to June 2019. Demographic data, vascular patency, and wound characteristics were recorded. Wound was irrigated before NPWT. An infra-red 3D camera (inSight ®, eKare, Fairfax, VA, USA) was used to capture digital photographs. Wound area and volume were measured. Measurements were taken weekly from before treatment to one month after using inSight ® cloud software. The risk factors of diabetic foot ulcers related to wound healing were evaluated. Results: NPWT resulted in significant area improvements for open diabetic foot ulcers (p = 0.001). Postoperative 1-week area change velocity was 1.35 cm2/day, peaking at 2 weeks (1.84 cm2/day). Volume also showed significant improvement over time (p = 0.001), with a 1-week peak velocity of 1.20 cm3/day. All peak area and volume changes occurred within two weeks after NPWT application. Midfoot and hindfoot exhibited higher velocity of volume than forefoot (p = 0.001). Postoperative volume change was the fastest with a patent peroneal artery. Conclusion: 3D wound assessment for velocity of granulation tissue filled in an open DFU after NPWT could be effective to predict outcomes. Most wound healing following NPWT in DFUs was completed within two weeks. Application of NPWT for an additional two weeks did not significantly impact the completion of wound healing even though midfoot and hindfoot exhibited higher velocity of volume than forefoot.

Advances in stem cell therapy for diabetic foot.

Diabetic Foot Ulcers (DFU) represent a grave complication often encountered in the advanced stages of diabetes mellitus. They frequently lead to recurrent hospitalizations and, in severe cases, can result in life-threatening conditions such as infections, gangrene, and even amputation Diabetic foot ulcers (DFU), as a serious complication in the late stage of diabetes mellitus, are prone to lead to repeated hospitalization, and in severe cases, infection, gangrene, and even amputation. Although there are many methods for treating diabetic foot, there is no clear and effective method to reduce the amputation rate of diabetic foot patients. In recent years, advancements in the understanding of stem cell therapy for the treatment of DFU have shed light on its potential as a novel therapeutic approach. In recent years, as the research on stem cell therapy for diabetic foot is gradually deepening, stem cells are expected to become a new therapeutic method for treating DFU in the future. Their therapeutic effects are through promoting angiogenesis, secreting paracrine factors, controlling inflammation, promoting collagen deposition, and regulating immunity, etc. Despite numerous studies confirming the efficacy of stem cell therapy in treating DFU, there is still a need for the establishment of standardized treatment protocols. Although numerous studies have shown that stem cell therapy for DFU is real and effective, there has not yet been a standardized treatment protocol. This article reviews studies related to stem cell therapy for DFU, looking at the mechanism of action, types of stem cells, and modes of administration.

Application of hyperbaric oxygen therapy in diabetic foot ulcers: A meta-analysis.

Hyperbaric oxygen therapy (HBOT) has been used in patients with diabetic foot ulcers (DFU) for many years, but its clinical efficacy is still controversial. Therefore, this study explored the efficacy of HBOT applied to DFU by means of meta-analysis. PubMed, Cochrane Library, Embase, CNKI and Wanfang databases were searched, from database inception to October 2023, and published randomised controlled trials (RCTs) of HBOT in DFU were collected. Two investigators independently screened the collected literature, extracted relevant data and assessed the quality of the literature. Review Manager 5.4 software was applied for data analysis. Twenty-nine RCTs with 1764 patients were included. According to the combined results, when compared with conventional treatment, HBOT significantly increased the complete healing rate of DFUs (46.76% vs. 24.46%, odds ratio [OR]: 2.83, 95% CI: 2.29-3.51, p < 0.00001) and decreased the amputation rate (26.03% vs. 45.00%, OR: 0.41, 95% CI: 0.18-0.95, p = 0.04), but the incidence of adverse events was significantly higher in patients (17.37% vs. 8.27%, OR: 2.49, 95% CI: 1.35-4.57, p = 0.003), whereas there was no significant difference in the mortality (6.96% vs. 12.71%, OR: 0.52, 95% CI: 0.21-1.28, p = 0.16). Our results suggest that HBOT is effective in increasing the complete healing rate and decreasing the amputation rate in patients with DFUs, but increases the incidence of adverse events, while it has no significant effect on mortality.

Hyperbaric Oxygen Therapy for Diabetic Foot Ulcers Based on Wagner Grading: A Systematic Review and Meta-analysis.

Diabetic foot ulcers (DFUs) are common complications of uncontrolled diabetes mellitus that can result in infection and amputation of the lower extremities. This study compared the benefits and risks of hyperbaric oxygen therapy with those of other DFU treatments, based on the Wagner grading system. Systematic searches for randomly controlled trials using hyperbaric oxygen therapy for DFUs were performed using PubMed, the Cochrane Library, and Embase. Data regarding demographics, wound healing, minor and major amputations, operative debridement, nonhealing wounds, and adverse effects were analyzed based on Wagner grades, using RevMan 5.4.1 and Microsoft Excel. Hyperbaric oxygen therapy was significantly superior to other treatments for wound healing rates 8 or more weeks after the final treatment (RR = 2.39; 1.87-3.05; P < 0.00001) minor/distal amputations (RR = 0.58; 0.43-0.80; P < 0.007), and major/proximal amputations (RR = 0.31; 0.18-0.52; P < 0.00001) for the 14 studies analyzed. In addition, this therapy increased the rate of complete wound healing for Wagner grades II (RR = 21.11; 3.05-146.03; P = 0.002), III (RR = 19.58; 2.82-135.94, P = 0.003), and IV (RR = 17.53; 2.45-125.44; P = 0.004); decreased the minor/distal amputation rate for grade III (RR = 0.06; 0.01-0.29; P = 0.0004) and the major/proximal amputation rate on for grade IV (RR = 0.08; 0.03-0.25; P < 0.0001); and decreased the operative debridement rate for Wagner grade II (RR = 0.09; 0.01-0.60; P = 0.01). Moderate-quality evidence revealed that adjunctive hyperbaric oxygen therapy improved DFU wound healing for Wagner grades II, III, and IV; prevented minor and major amputations for grades III and IV, respectively; and prevented operative debridement in grade II wounds.

IDF23-0133 Monitoring negative pressure wound therapy for diabetic foot ulcers using WhatsApp

IDF23-0133 Monitoring negative pressure wound therapy for diabetic foot ulcers using WhatsApp

HMOX1 as a therapeutic target associated with diabetic foot ulcers based on single-cell analysis and machine learning.

Diabetic foot ulcers (DFUs) are a serious chronic complication of diabetes mellitus and a leading cause of disability and death in diabetic patients. However, current treatments remain unsatisfactory. Although macrophages are associated with DFU, their exact role in this disease remains uncertain. This study sought to detect macrophage-related genes in DFU and identify possible therapeutic targets. Single-cell datasets (GSE223964) and RNA-seq datasets (GSM68183, GSE80178, GSE134431 and GSE147890) associated with DFU were retrieved from the gene expression omnibus (GEO) database for this study. Analysis of the provided single-cell data revealed the distribution of macrophage subpopulations in the DFU. Four independent RNA-seq datasets were merged into a single DFU cohort and further analysed using bioinformatics. This included differential expression (DEG) analysis, multiple machine learning algorithms to identify biomarkers and enrichment analysis. Finally, key results were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western bolt. Finally, the findings were validated using RT-qPCR and western blot. We obtained 802 macrophage-related genes in single-cell analysis. Differential expression analysis yielded 743 DEGs. Thirty-seven macrophage-associated DEGs were identified by cross-analysis of marker genes with macrophage-associated DEGs. Thirty-seven intersections were screened and cross-analysed using four machine learning algorithms. Finally, HMOX1 was identified as a potentially valuable biomarker. HMOX1 was significantly associated with biological pathways such as the insulin signalling pathway. The results showed that HMOX1 was significantly overexpressed in DFU samples. In conclusion, the analytical results of this study identified HMOX1 as a potentially valuable biomarker associated with macrophages in DFU. The results of our analysis improve our understanding of the mechanism of macrophage action in this disease and may be useful in developing targeted therapies for DFU.

Evidence for the benefits of negative pressure therapy in the treatment of diabetic foot in adults: a comprehensive approach to improved health

Diabetic foot ulcers represent an increase in recent years in the cures to be carried out by nursing staff. For this reason, the new negative pressure therapy has been chosen, which involves an increase in granulation tissue, leading to complete healing in a minimum time, highlighting the few complications derived from said therapy. Objective: To demonstrate the effectiveness of negative pressure therapy in patients with diabetic foot. Methodology: A narrative review was carried out between December 2022 and November 2023 in the databases of Pubmed, Dialnet, Google Scholar, WOS, Scopus and Cochrane, following a search string, which combines keywords derived from the thesauri “Health Sciences Descriptors” (DeCS) and “Medical Subject Headings” (MeSH), being combined with the Boolean operators “NOT”, “OR” and “AND”. Results: Negative pressure therapy offers a number of significant benefits for adult patients with diabetic foot, improving wound healing, reducing the risk of serious complications and contributing to a better quality of life. It is important to highlight that the implementation of this therapy must be guided by health professionals and adapted to the specific needs of each patient. Conclusion: After comparing the different selected articles, it was determined that the application of negative pressure therapy in diabetic foot ulcers is beneficial in relation to the reduction in healing time compared to conventional wound healing dressings. The associated complications being minimal. Furthermore, treatment with this therapy turns out to be cost-effective by reducing patients' hospital stays, leading to an increase in quality of life.

Effectiveness of Stem Cell Therapy for Diabetic Foot Ulcers: A Systematic Review and GRADE Compliant Bootstrapped Meta-Analysis of Randomized Clinical Trials.

Diabetic foot (DF) represents a severe complication of diabetes mellitus, imposing substantial psychological and economic burdens on affected individuals. This investigation sought to assess the therapeutic efficacy of stem cell interventions in the management of DF complications. A comprehensive systematic search across PubMed, Embase, CINAHL, Scopus, and the Cochrane library databases was conducted to identify pertinent studies for meta-analysis. Outcome measures encompassed ulcer or wound healing rates, amputation rates, angiogenesis, ankle-brachial index (ABI), and pain-free walking distance. Dichotomous outcomes were expressed as risk differences (RDs) with 95% confidence intervals (CIs), while continuous data were articulated as standardized mean differences (SMDs) with corresponding 95% CIs. Statistical analyses were executed using RevMan 5.3 and Open Meta, with bootstrapped meta-analysis conducted through OpenMEE software. A total of 20 studies, comprising 24 arms and involving 1304 participants, were incorporated into the meta-analysis. The findings revealed that stem cell therapy exhibited superior efficacy compared to conventional interventions in terms of ulcer or wound healing rate [RD = 0.36 (0.28, 0.43)], pain-free walking distance [SMD = 1.27 (0.89, 1.65)], ABI [SMD = 0.61 (0.33, 0.88)], and new vessel development [RD = 0.48 (0.23, 0.78)], while concurrently reducing the amputation rate significantly [RD = -0.19 (-0.25, -0.12)]. Furthermore, no statistically significant difference in adverse events was observed [RD -0.07 (-0.16, 0.02)]. The Grading of Recommendations, Assessment, Development, and Evaluation assessment indicated varying levels of evidence certainty, ranging from very low to moderate, for different outcomes. Bootstrapping analysis substantiated the precision of the results. The meta-analysis underscores the significant superiority of stem cell therapy over conventional approaches in treating DF complications. Future investigations should prioritize large-scale, randomized, double-blind, placebo-controlled, multicenter trials, incorporating rigorous long-term follow-up protocols. These studies are essential for elucidating the optimal cell types and therapeutic parameters that contribute to the most effective treatment strategies for DF management.

A systematic review of efficacy on larva debridement in diabetic foot ulcers

Larva therapy, also known as maggot therapy, biodebridement, or maggot debridement therapy, involved the application of live fly larva to a patient’s wound for debridement, disinfection, and wound healing. Despite its wide application in diabetic foot ulcers, the efficacy of this intervention remains uncertain. This review aimed to examine the benefits of larva therapy in diabetic foot ulcers by conducting systematic review. This systematic review sought relevant articles using MeSH-based keywords in databases such as Scopus, PubMed, Science Direct, and ProQuest. The inclusion criteria for the articles were as follows: population - patients with diabetic foot ulcers, intervention - the use of debridement or therapeutic application of maggot therapy with Lucilia sericata, comparison - none, outcome - the results of articles demonstrating the effectiveness of using Lucilia sericata maggot therapy on diabetic foot ulcers. Article quality assessment was conducted using the Joanna Briggs Institute guidelines. Descriptive analysis was performed with a narrative approach, considering articles published from 2018 to 2023. Based on the literature search, 237 articles were found with matching keywords from Scopus (103), PubMed (77), Science Direct (14), and ProQuest (43). After screening for inclusion and exclusion criteria, 11 articles were identified for inclusion in this review. These 11 articles indicate that larva therapy can be an effective method in treating diabetic foot ulcers, especially when used correctly and tailored to each patient’s condition and needs. Green bottle fly larva, Lucilia sericata, produce proteolytic enzymes that can assist in wound healing. Larva therapy is effective when combined with other procedures. In clinical practice, it is highly recommended that nurses provide an individualized approach and assess potential side effects.

Evaluation of the healing potential of short-term ozone therapy for the treatment of diabetic foot ulcers.

The availability of research on short-term ozone therapy for diabetic foot ulcers (DFUs) is limited, and even when it is accessible, it mainly comprises of basic analysis conducted during long-term ozone therapy. This study was to evaluate the efficacy of short-term ozone therapy in promoting wound healing in DFUs. A retrospective analysis was conducted on 89 patients with type 2 diabetes complicated by DFUs. The patients were divided into two groups: ozone therapy group (n=41) and control group (n=48). Wound condition, change of bacterial types, changes in inflammatory indicators (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and procalcitonin [PCT]), vascular endothelial growth factor (VEGF), cytokines [Interleukin 6 (IL-6) and tumor necrosis factor-α(TNF-α)], and oxidative stress levels (superoxide dismutase [SOD], malondialdehyde [MDA], and total antioxidant capacity [T-AOC]) were observed pre-treatment and after 1 week. After a 12-week of follow-up, wound healing rate, amputation rate, inpatient day, duration of antibiotics, reinfection rate, incidence of new ulcers, readmission rate, and reoperation rate, and cumulative wound healing rate using Kaplan-Meier curves were assessed. After 1 week of treatment, the ozone therapy group showed higher VEGF, SOD, and T-AOC levels compared to the control group (P<0.05), while CRP, PCT, ESR, IL-6, TNF-α, MDA levels and bacterial types were lower (P<0.05). The ozone therapy group had a higher wound healing rate after a 12-week follow-up (P<0.05). Kaplan-Meier curves indicated a higher cumulative wound healing rate in the ozone therapy group (P<0.05). Additionally, the ozone therapy group had lower inpatient day, duration of antibiotics, reinfection rate, and readmission rate compared to the control group (P<0.05). Short-term ozone therapy is effective in promoting wound healing in DFUs by reducing inflammation, increasing growth factor levels, improving oxidative stress status, shortening healing time, and improving long-term prognosis. These findings suggest the potential of short-term ozone therapy as a valuable treatment modality for DFUs.

Monitoring negative pressure wound therapy for diabetic foot ulcers using WhatsApp

Foot complications of patients with diabetes could lead to amputations and early death. Diabetic foot ulcers (DFU) are usually difficult to treat and impose huge financial burden. Monitoring wound progress is the mainstay of any treatment and alternatives to face-to-face consultations such as tele-medicine have been proposed. Very few papers explored the utility and effectiveness of monitoring DFU through instant messaging application such as WhatsApp. The aim of this study is to evaluate the validity of WhatsApp in monitoring diabetic wounds treated with negative pressure wound therapy (NPWT).Twenty-two patients were prospectively recruited. All patients had an initial face-to-face consultation and debridement. Dressings were changed twice per week at patient's residence and media files were sent by the wound nurse via Short Message Service (SMS). A subsequent face to face consultation was scheduled whenever a complication was suspected. The primary outcomes were the percentages of accurate cases a) where a new or recurrent infection was suspected, and a b) where a debridement was thought to be needed.Complete healing of the defect using NPWT was achieved in 10 patients and a skin graft procedure was needed in another 4 patients. Five patients needed further surgical debridement. Failure to heal was observed in 3 patients. Out of the seven cases where a new infection was suspected, five (71.5%) were confirmed on face-to-face consultation. No confirmed cases of infection were observed during follow-up for those estimated as clean. Out of the 11 cases where debridement was favored based on WhatsApp media files, confirmation of a needed debridement was recorded in 8 (73%) cases.NPWT monitoring of for diabetic foot and leg ulcers using WhatsApp application was found to be an excellent method to document and track the wound process and complications. The excellent specificity and high sensibility should encourage for common use by healthcare. The results of this study could be also valuable for patients living in rural areas and in case of future pandemics.

Engineered exosomes as a prospective therapy for diabetic foot ulcers.

Diabetic foot ulcer (DFU), characterized by high recurrence rate, amputations and mortality, poses a significant challenge in diabetes management. The complex pathology involves dysregulated glucose homeostasis leading to systemic and local microenvironmental complications, including peripheral neuropathy, micro- and macro-angiopathy, recurrent infection, persistent inflammation and dysregulated re-epithelialization. Novel approaches to accelerate DFU healing are actively pursued, with a focus on utilizing exosomes. Exosomes are natural nanovesicles mediating cellular communication and containing diverse functional molecular cargos, including DNA, mRNA, microRNA (miRNA), lncRNA, proteins, lipids and metabolites. While some exosomes show promise in modulating cellular function and promoting ulcer healing, their efficacy is limited by low yield, impurities, low loading content and inadequate targeting. Engineering exosomes to enhance their curative activity represents a potentially more efficient approach for DFUs. This could facilitate focused repair and regeneration of nerves, blood vessels and soft tissue after ulcer development. This review provides an overview of DFU pathogenesis, strategies for exosome engineering and the targeted therapeutic application of engineered exosomes in addressing critical pathological changes associated with DFUs.

Quality of evidence supporting the role of hyperbaric oxygen therapy for diabetic foot ulcers.

The goal of this overview of systematic reviews (SRs) and meta-analyses (MAs) was to methodically gather, evaluate and summarize the data supporting the use of hyperbaric oxygen therapy (HBOT) to treat diabetic foot ulcers (DFUs). The Cochrane Library, Embase, PubMed, Web of Science and Embase were all searched thoroughly to identify SRs/MAs that qualified. AMSTAR-2 tool, PRISMA checklists and GRADE system were applied by two reviewers independently to assess the methodological quality, reporting and evidence quality of the included SRs/MAs, respectively. Eleven SRs/MAs were enrolled in this overview. According to AMSTAR-2, a very low methodological quality assessment was given to the included SRs/MAs due to the limitations of items 2, 4 and 7. For the PRISMA, the overall quality of reporting is not satisfactory due to missing reporting on protocol, search, as well as additional analysis. The majority of outcomes had low- to moderate-quality evidence, and no high-quality evidence was found to support the role of HBOT for DFUs, according to GRADE. To conclude, the potential of HBOT in treating DFUs is supported by evidence of low to moderate quality. More rigorously designed, high-level studies are needed in the future to determine the evidence for HBOT for DFU, including the timing, frequency and duration of HBOT interventions.

Honey Therapy in Diabetic Foot Ulcers: A Promising Strategy for Effective Wound Healing

Diabetic foot ulcers (DFUs) are considered a major problem for public health, leading to high rates of lower-limb amputations. Moreover, due to the high prevalence rate of predisposing factors, the incidence rate of DFU is still rising. Although DFUs are complex in nature, foot ulceration usually precedes diabetic foot amputations. These impaired chronic wounds usually promote a microbial biofilm, commonly characterized by the presence of multidrug-resistant microorganisms, hampering the efficacy of conventional antibiotic treatments. Honey has been shown to be an effective antibacterial component, including against multidrug-resistant bacteria. Honey’s physical–chemical characteristics, such as the presence of hydrogen peroxide, its low pH levels, and its high sugar and phenolic contents, promote anti-inflammatory and antioxidative activities, improving wound healing. This review aims to explore honey’s effects in wound healing, especially for DFUs, and to show how the different physical–chemical features among different honey types might influence the treatment’s effectiveness. For this, the mechanisms by which honey can promote wound healing and the potential use of honey dressings in diabetic wounds were investigated in animal models and humans. After revising the diabetic wound impairment mechanisms, we found that most of the clinical studies that treated DFUs with honey in animal models or humans reported accelerated wound healing, greater wound contraction, and lower amputation or hospitalization rates; however, few studies characterized the features of honeys used for wound treatment, hindering the possibility of extensively comparing the different types of honey and identifying characteristics that most successfully promote wound healing. According to this review, honey is a cost-effective and safe option for DFU management.

Use of Ozone Therapy in Diabetic Foot Ulcers.

ozone therapy is a therapy composed of ozone. This gas is in the atmosphere with various general effects: direct disinfectant and trophic effects and a systemic antibacterial and antiviral effect. This gas also improves blood circulation, makes glucose metabolism more effective, improves erythrocyte metabolism, and improves fatty acid metabolism. Provide evidence of the effectiveness of ozone therapy in wounds of patients with diabetic foot. Analyze the effectiveness of ozone therapy compared to other treatments to achieve good wound healing in patients with diabetic foot. To study the benefits of the use of ozone therapy in ulcers of patients. Analyze the management of ozone therapy and other treatments to achieve healing of ulcers in patients. A bibliographic review focused on articles published between November 2014 and June 2023 was carried out. The following databases were consulted: Pubmed (Medline), Dialnet, Google Scholar, Web of Science (WOS), Scielo, and Scopus. After applying the article selection criteria and evaluating the quality of the methodology, a total of 17 articles were obtained. The results affirm ozone therapy as promising for the treatment of wounds in patients with diabetic foot. the evidence has been able to determine that ozone therapy is adequate for the treatment of diabetic foot ulcers. In addition, the therapy has been shown to be effective, safe, and beneficial, with few adverse effects for the treatment of diabetic foot ulcers.

Case Study of Ozone Bagging Adjuvant Therapy in Wagner II and III Diabetic Foot Ulcers on Wound Healing Process: Three Patients Recovered Completely

Background: Diabetic foot ulcer is a chronic complication of diabetes mellitus in the form of ulceration with or without infection. Diabetic foot ulcers that are not handled properly can cause damage to the foot that requires amputation. Wound care techniques for treating diabetic foot ulcers are starting to develop, one of which is ozone bagging therapy. This ozone bagging therapy in diabetic foot ulcers is reported to be useful as an anti-microbial effect, increasing glycemic control, increasing insulin sensitivity, preventing oxidative stress, increasing fibroblast proliferation, and increasing the release of growth factors. This case study will report 3 patients with Wagner II and III-foot ulcers who healed completely within 28 days using ozone bagging treatment as an adjuvant. Methods: 3 patients with diabetic foot ulcers Wagner II and III received ozone bagging therapy every 4 days for 7 sessions (a total of 28 days) as an additional therapy besides treating moist gauze using NaCl. This study used a Medical Ozone Generator. The dose of ozone used with medical oxygen is 1 lpm, flow 0.6, in the first session "high dose" with an output dose of 80-100 mg/l and in the 2nd-7th session with a low dose (25-35 mg/l). Macroscopic assessment of the wound using the Wagner scale and the progress of each treatment session is documented in photographs. Results: On macroscopic measurements, the process of wound healing leading to wound closure was better in the treatment group and was taken as a case for 3 patients who recovered completely. It resulted in 3 patients who recovered completely with a measurement of the Meggitt-Wagner scale of 0.26. Conclusion: For these recovered patients, there was a decrease in VEGF, TGF-β, and PDGF levels. The VEGF, TGF-β, and PDGF levels tested were VEGF, TGF-β, and PDGF levels in wound exudate by comparing them on the 3rd day. 1st and 12th day. Supported by macroscopic data showing that the wound healing process was better in the group that received ozone bagging therapy as an adjuvant. From this study it was found that the trend of decreasing levels of VEGF, TGF-β, and PDGF in wound exudate occurred because the inflammatory and proliferative processes in the treatment group lasted more faster than the control group. Keywords: ozone bagging therapy, diabetic ulcers, wound exudate, growth factors, VEGF, TGF-β, and PDGF, Meggitt-Wagner scale.

Poly(pentahydropyrimidine)‐Based Hybrid Hydrogel with Synergistic Antibacterial and Pro‐Angiogenic Ability for the Therapy of Diabetic Foot Ulcers

AbstractBacterial infection and impaired angiogenesis make the treatment of diabetic foot ulcers (DFU) extremely challenging. Cationic polymers are expected to treat infected wounds due to their excellent antibacterial properties, but still, it is difficult to meet the therapeutic needs of pro‐angiogenesis and anti‐infections due to their simple construction units and outmoded synthesis methods. Herein, a cationic poly(pentahydropyrimidine) (PPHP) library with strong modifiability is synthesized to construct a hybrid hydrogel with synergistic therapeutic effects for the treatment of infected DFUs. It is found that the as‐synthesized hybrid hydrogel can up‐regulate angiogenesis‐related gene (HIF‐1, VEGF, and bFGFR/bFGF) expression and targeted disruption of bacterial cell membranes, which finally promotes the healing of infected DFU (wound healing rate: 92%) within 10 days. This hydrogel, thus, holds great promise in developing new strategies to significantly enhance the treatment of DFU and other bacterial‐infected pathological diagnoses.

Gene therapy for diabetic foot ulcers: Interim analysis of a randomised, placebo-controlled phase 3 study of VM202 (ENGENSIS), a plasmid DNA expressing two isoforms of human hepatocyte growth factor.

To evaluate the status of a 7-month phase 3 study conducted to test the effect of intramuscular injections of VM202 (ENGENSIS), a plasmid DNA encoding human hepatocyte growth factor, into the calf muscles of chronic nonhealing diabetic foot ulcers with concomitant peripheral artery disease. The phase 3 study, originally aimed to recruit 300 subjects, was discontinued because of slow patient recruitment. An unprespecified interim analysis was performed for the 44 subjects enrolled to assess the status and determine the future direction. Statistical analyses were carried out for the Intent-to-Treat (ITT) population and separately for subjects with neuroischemic ulcers, using a t-test and Fisher's exact test. A logistic regression analysis was also conducted. VM202 was safe and potentially should have benefits. In the ITT population (N = 44), there was a positive trend toward closure in the VM202 group from 3 to 6 months but with no statistical significance. Levels of ulcer volume or area were found to be highly skewed between the placebo and VM202 groups. Forty subjects, excluding four outliers in both arms, showed significant wound-closing effects at month 6 (P = .0457). In 23 patients with neuroischemic ulcers, the percentage of subjects reaching complete ulcer closure was significantly higher in the VM202 group at months 3, 4, and 5 (P = .0391, .0391, and .0361). When two outliers were excluded, a significant difference was evident in months 3, 4, 5, and 6 (P = .03 for all points). A potentially clinically meaningful 0.15 increase in Ankle-Brachial Index was observed in the VM202 group at day 210 in the ITT population (P = .0776). Intramuscular injections of VM202 plasmid DNA to calf muscle may have promise in the treatment of chronic neuroischemic diabetic foot ulcers (DFUs). Given the safety profile and potential healing effects, continuing a larger DFU study is warranted with modifications of the current protocol and expansion of enrolling sites.

Extracorporeal shockwave therapy for diabetic foot ulcers: a feasibility study

The purpose of this study was to assess the feasibility of delivering extracorporeal shockwave therapy (ESWT) to patients with diabetic foot ulcers (DFUs). It also aimed to explore any potential clinical effect of ESWT on wound healing and investigate whether ESWT offers any patient-reported benefits. In this single-centre, mixed methods feasibility study, patients with a DFU who met the eligibility criteria underwent ESWT three times over a seven-day period. Primary outcome was feasibility of delivering the intervention. Secondary outcomes included wound size, number of DFUs healed at 12 weeks and quality of life (QoL). Semi-structured interviews explored participants' experience of undergoing ESWT. Of 106 patients screened, 24 (22.6%) were recruited. Following recruitment, two patients were withdrawn from the study with 22 patients included in the final analysis. The mean attendance at clinic was 90.9% and 65.1% for follow-up. The mean score for acceptability and tolerability was 9.86±0.48 (95% confidence interval (CI): 9.62-10.01) and 9.15±2.57 (95% CI: 7.87-10.42), respectively. There were no serious adverse events or side-effects. Of the DFUs, 45.5% healed during follow-up and QoL scores improved until eight weeks. Key themes identified from the qualitative interviews were: desire for fast healing; improved QoL; flexibility of new treatments; and accessibility of transport. This study has shown that it is possible to recruit and retain patents into a single-arm study of ESWT for DFUs. This study supports development of a large randomised control trial to determine the clinical and cost-effectiveness of ESWT for DFU healing.