Search Results (218)

Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study aimed to evaluate the impact of HBOT on systemic biomarkers, local microvasculature, and clinical outcomes in patients with DFUs. Methods: In this non-randomized prospective study, 20 patients with ischemic DFUs were followed over a 36-month period. Fourteen received HBOT in addition to standard care, while six received standard care alone. Clinical outcomes—including DFU resolution, recurrence, lower extremity amputation (LEA), and mortality—were assessed alongside systemic inflammatory and angiogenic biomarkers and wound characteristics at baseline and at 3, 6, 12, and 36 months. CD31 immunostaining was performed on available tissue samples. Results: The two groups were comparable at baseline (mean age 62 ± 12 years; diabetes duration 18 ± 9 years). At 3 months, the HBOT group showed significant reductions in erythrocyte sedimentation rate and DFU size (p < 0.05), with downward trends observed in C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and an increase in stromal-derived factor-1 alpha (SDF1-α). No significant changes were observed in the control group. CD31+ microvessel density appeared to increase in HBOT-treated DFU tissue after one month, although the sample size was limited. Patients receiving HBOT had lower rates of LEA and mortality, improved wound healing, and sustained outcomes over three years. DFU recurrence rates were similar between groups. Conclusions: HBOT was associated with improved wound healing and favorable biomarker profiles in patients with treatment-resistant ischemic DFUs. While these findings are encouraging, the small sample size and non-randomized design limit their generalizability, highlighting the need for larger, controlled studies. Full article

Objective: To develop and validate a ResNet-50-based deep learning model for automatic detection of osteomyelitis (DFO) in plain radiographs of patients with diabetic foot ulcers (DFUs). Research Design and Methods: This retrospective study included 168 patients with type one or type two diabetes and clinical suspicion of DFO confirmed via a surgical bone biopsy. An experienced clinician and a pretrained ResNet-50 model independently interpreted the radiographs. The model was developed using Python-based frameworks with ChatGPT assistance for coding. The diagnostic performance was assessed against the histopathological findings, calculating sensitivity, specificity, the positive predictive value (PPV), the negative predictive value (NPV), and the likelihood ratios. Agreement between the AI model and the clinician was evaluated using Cohen’s kappa coefficient. Results: The AI model demonstrated high sensitivity (92.8%) and PPV (0.97), but low-level specificity (4.4%). The clinician showed 90.2% sensitivity and 37.8% specificity. The Cohen’s kappa coefficient between the AI model and the clinician was −0.105 (p = 0.117), indicating weak agreement. Both the methods tended to classify many cases as DFO-positive, with 81.5% agreement in the positive cases. Conclusions: This study demonstrates the potential of IA to support the radiographic diagnosis of DFO using a ResNet-50-based deep learning model. AI-assisted radiographic interpretation could enhance early DFO detection, particularly in high-prevalence settings. However, further validation is necessary to improve its specificity and assess its utility in primary care. Full article

Diabetic foot ulcers (DFUs) are a serious complication of diabetes, associated with high recurrence and amputation rates. Adherence to offloading devices is critical for wound healing but remains inadequately monitored in real-world settings. This study evaluates the SmartBoot edge-computing system—a wearable, real-time remote monitoring solution integrating an inertial measurement unit (Sensoria Core) and smartwatch—for its validity in quantifying cadence and step count as digital biomarkers of frailty, and for detecting adherence. Twelve healthy adults wore two types of removable offloading boots (Össur and Foot Defender) during walking tasks at varied speeds; system outputs were validated against a gold-standard wearable and compared with staff-recorded adherence logs. Additionally, user experience was assessed using the Technology Acceptance Model (TAM) in healthy participants (n = 12) and patients with DFU (n = 81). The SmartBoot demonstrated high accuracy in cadence and step count across conditions (bias < 5.5%), with an adherence detection accuracy of 96% (Össur) and 97% (Foot Defender). TAM results indicated strong user acceptance and perceived ease of use across both cohorts. These findings support the SmartBoot system’s potential as a valid, scalable solution for real-time remote monitoring of adherence and mobility in DFU management. Further clinical validation in ongoing studies involving DFU patients is underway. Full article

Background/Objectives: We evaluated the diabetic foot ulcer (DFU) microbiome in clinical situations identified as risk factors for a worse outcome and explored the roles of the most abundant microorganisms. Methods: A prospective multicenter cohort of diabetic patients with DFU were followed up for 6 months. We obtained a DFU tissue biopsy for microbiome analysis at the baseline visit. Genomic DNA was extracted (QIAamp DNA Mini Kit, Qiagen, Hilden, Germany) and quantified (QuantiFluor dsDNA System, Promega, Madison, WI, USA), with analysis of bacterial communities focusing on relative abundances (RA) and on alpha and beta diversity. Results: Overall, 59 DFUs were analyzed. DFUs of long duration (≥4 weeks) presented a higher RA of Gammaproteobacteria compared with ulcers of short duration (p = 0.02). Non-infected DFUs had a higher proportion of Actinobacteriota phyla than infected DFUs and, particularly, a higher RA of Corynebacterium genera (means ± SD: 0.063 ± 0.14 vs. 0.028 ± 0.13, respectively; p = 0.03). Regarding the pathogenic role of Staphylococcus aureus, DFUs with low S. aureus bacterial loads (<10⁶ CFU/mL) compared with those with high loads (≥10⁶ CFU/mL) showed a higher Corynebacterium RA (0.045 ± 0.08 vs. 0.003 ± 0.01, respectively; p = 0.01). Conclusions: In clinical situations associated with poor DFU outcomes, we observed a predominance of Gammaproteobacteria in the microbiome of long-duration ulcers and a higher RA of Corynebacterium in non-infected DFUs. An inverse relationship between the predominance of Corynebacterium and the S. aureus bacterial load in DFUs was also noted, which may suggest these commensals have a modulatory role. Further studies should explore the clinical utility of microbiome analysis for DFUs. Full article

Diabetic foot ulcers (DFUs), which affect approximately 15% of individuals with diabetes mellitus (DM), result from complex molecular disturbances involving chronic hyperglycemia, immune dysfunction, and infection. At the molecular level, chronic hyperglycemia promotes the formation of advanced glycation end products (AGEs), activates the AGE-RAGE-NF-κB axis, increases oxidative stress, and impairs macrophage polarization from the pro-inflammatory M1 to the reparative M2 phenotype, collectively disrupting normal wound healing processes. The local wound environment is further worsened by antibiotic-resistant polymicrobial infections, which sustain inflammatory signaling and promote extracellular matrix degradation. The rising threat of antimicrobial resistance complicates infection management even further. Recent studies emphasize that optimal glycemic control using antihyperglycemic agents such as metformin, Glucagon-like Peptide 1 receptor agonists (GLP-1 receptor agonists), and Dipeptidyl Peptidase 4 enzyme inhibitors (DPP-4 inhibitors) improves overall metabolic balance. These agents also influence angiogenesis, inflammation, and tissue regeneration through pathways including AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and vascular endothelial growth factor (VEGF) signaling. Evidence indicates that maintaining glycemic stability through continuous glucose monitoring (CGM) and adherence to antihyperglycemic treatment enhances antibiotic effectiveness by improving immune cell function and reducing bacterial virulence. This review consolidates current molecular evidence on the combined effects of glycemic and antibiotic therapies in DFUs. It advocates for an integrated approach that addresses both metabolic and microbial factors to restore wound homeostasis and minimize the risk of severe outcomes such as amputation. Full article

Diabetic foot ulcers (DFUs) represent a critical global health issue, necessitating the development of advanced smart, flexible, and wearable sensors for continuous monitoring that are reimbursable within foot orthotics. This study presents the design and characterization of a pressure sensor implemented into a shoe insole to monitor diabetic wound pressures, emphasizing the need for a high sensitivity, durability under cyclic mechanical loading, and a rapid response time. This investigation focuses on the electrical and mechanical properties of carbon nanotube (CNT) composites utilizing Ecoflex and polydimethylsiloxane (PDMS). Morphological characterization was conducted using Transmission Electron Microscopy (TEM), Laser Confocal Microscopy, and Scanning Electron Microscopy (SEM). The electrical and mechanical properties of the CNT/Ecoflex- and the CNT/PDMS-based sensor composites were then investigated. CNT/Ecoflex was then further evaluated due to its lower variability performance between cycles at the same pressure, as well as its consistently higher capacitance values across all trials in comparison to CNT/PDMS. The CNT/Ecoflex composite sensor showed a high sensitivity (2.38 to 3.40 kPa⁻¹) over a pressure sensing range of 0 to 68.95 kPa. The sensor’s stability was further assessed under applied pressures simulating human weight. A custom insole prototype, incorporating 12 CNT/Ecoflex elastomeric matrix-based sensors (as an example) distributed across the metatarsal heads, midfoot, and heel regions, was developed and characterized. Capacitance measurements, ranging from 0.25 pF to 60 pF, were obtained across N = 3 feasibility trials, demonstrating the sensor’s response to varying pressure conditions linked to different body weights. These results highlight the potential of this flexible insole prototype for precise and real-time plantar surface monitoring, offering an approachable avenue for a challenging diabetic orthotics application. Full article

Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes and are characterized by impaired wound healing and a high amputation risk. Exosomes—which are nanovesicles carrying proteins, RNAs, and lipids—mediate intercellular communication in wound microenvironments, yet their biomarker potential in DFUs remains underexplored. Methods: We analyzed transcriptomic data from GSE134431 (13 DFU vs. 8 controls) as a training set and validated findings in GSE80178 (6 DFU vs. 3 controls). A sum of 7901 differentially expressed genes (DEGs) of DFUs were detected and intersected with 125 literature-curated exosome-related genes (ERGs) to yield 51 candidates. This was followed by GO/KEGG analyses and a PPI network construction. Support vector machine–recursive feature elimination (SVM-RFE) and the Boruta random forest algorithm distilled five biomarkers (DIS3L, EXOSC7, SDC1, STX11, SYT17). Expression trends were confirmed in both datasets. Analyses included nomogram construction, functional and correlation analyses, immune infiltration, GSEA, gene co-expression and regulatory network construction, drug prediction, molecular docking, and RT-qPCR validation in clinical samples. Results: A nomogram combining these markers achieved an acceptable calibration (Hosmer–Lemeshow p = 0.0718, MAE = 0.044). Immune cell infiltration (CIBERSORT) revealed associations between biomarker levels and NK cell and neutrophil subsets. Gene set enrichment analysis (GSEA) implicated IL-17 signaling, proteasome function, and microbial infection pathways. A GeneMANIA network highlighted RNA processing and vesicle trafficking. Transcription factor and miRNA predictions uncovered regulatory circuits, and DGIdb-driven drug repurposing followed by molecular docking identified Indatuximab ravtansine and heparin as high-affinity SDC1 binders. Finally, RT-qPCR validation in clinical DFU tissues (n = 5) recapitulated the bioinformatic expression patterns. Conclusions: We present five exosome-associated genes as novel DFU biomarkers with diagnostic potential and mechanistic links to immune modulation and vesicular transport. These findings lay the groundwork for exosome-based diagnostics and therapeutic targeting in DFU management. Full article

Background/Objectives: Advanced wound healing biologics for diabetic foot ulcer (DFU) are typically withheld from persons who are at high risk for amputation. However, a prospective, single-center cohort study evaluated the use of an advanced biologic, dehydrated amniotic (DAMA) tissue as early treatment for DFUs in patients with a high risk for amputation, demonstrating benefit for a small sample. This is the report of the five-year follow-up of those high-risk participants. Methods: This chart review provides a 5-year follow-up of 18 of 20 participants in the original study. The data were collected by medical record review. Specific data points included mortality, re-ulceration and additional ulceration, amputation (minor and major), end-stage renal disease with dialysis dependence, hospitalization, and limb-threatening ischemia. Results: The 5-year mortality rate from the time of wound healing was 50% (9/18 deceased). Four of the eighteen participants (22.2%) underwent major amputation within 5 years of study completion. Two had amputations of the study limb and two had amputations of the contralateral limb. Fifty percent (2/4) of those who had amputations died within 5 years after the major amputation. Over fifty percent (55.5% or 10 out of 18) of the participants experienced the re-ulceration of the original study ulcer and 94% (17 out of 18) developed a new site ulceration. A total of 25% of the hospitalizations over the 5 years were related to DFU (infection, osteomyelitis, and sepsis). Conclusions: This small-sample 5-year follow-up shows that early treatment with dehydrated amniotic (DAMA) tissue in patients with diabetic foot ulcers of moderate-to-high amputation risk results in similar outcomes as noted in the current research on patients with low risk for amputation. In fact, this paper may suggest that advanced biologics can safely be used for early treatment in moderate-to-high amputation risk without increasing mortality and amputation over 5 years. Full article

Objective: This study aims to elucidate the potential mechanisms by which Fespixon cream promotes diabetic foot ulcer (DFU) healing using network pharmacology, molecular docking, and RT-qPCR validation in clinical tissue samples. Methods: Active components of Fespixon cream were screened from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and relevant literature, and their corresponding targets were standardized using the Universal Protein Resource (UniProt) database. Diabetic foot ulcer (DFU)-related targets were retrieved and filtered from the GeneCards database and the Online Mendelian Inheritance in Man (OMIM) database. The intersection of drug and disease targets was identified, and a protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The interaction network was visualized using Cytoscape version 3.7.2 software. The potential mechanisms of the shared targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using R software packages, and results were visualized through Bioinformatics online tools. Molecular docking was performed to validate the binding between key active compounds of Fespixon cream and core DFU targets using AutoDock Vina version 1.1.2 and PyMOL software. Furthermore, RT-qPCR analysis was performed on wound edge tissue samples from DFU patients treated with Fespixon cream to experimentally verify the mRNA expression levels of predicted hub genes. Results: Network pharmacology analysis identified eight active compounds in Fespixon cream, along with 153 potential therapeutic targets related to diabetic foot ulcer (DFU). Among these, 21 were determined as core targets, with the top five ranked by degree value being RAC-αserine/threonine-protein kinase (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Interleukin-6 (IL6), and Mitogen-activated protein kinase 1 (MAPK1). GO enrichment analysis indicated that the targets of Fespixon cream were primarily involved in various biological processes related to cellular stress responses. KEGG pathway enrichment revealed that these targets were significantly enriched in pathways associated with diabetic complications, atherosclerosis, inflammation, and cancer. Molecular docking confirmed stable binding interactions between the five major active compounds—quercetin, apigenin, rosmarinic acid, salvigenin, and cirsimaritin—and the five core targets (AKT1, TP53, TNF, IL6, MAPK1). Among them, quercetin exhibited the strongest binding affinity with AKT1. RT-qPCR validation in clinical DFU tissue samples demonstrated consistent expression trends with computational predictions: AKT1 was significantly upregulated, while TP53, TNF, IL6, and MAPK1 were markedly downregulated in the Fespixon-treated group compared to controls (p < 0.001), supporting the proposed multi-target therapeutic mechanism. Conclusions: Our study reveals the potential mechanisms by which Fespixon cream exerts therapeutic effects on DFUs. The efficacy of Fespixon cream in treating DFUs is attributed to the synergistic actions of its bioactive components through multiple targets and multiple signaling pathways. Full article

Diabetic foot ulcers (DFUs) constitute a severe and debilitating complication of diabetes, imposing a substantial global health burden due to their intricate pathophysiology and impaired wound healing processes. Vitamin D deficiency is highly prevalent among diabetic populations, and accumulating evidence indicates its potential involvement in the pathogenesis and prognosis of DFUs. This review comprehensively explores the diverse roles of vitamin D in DFUs, encompassing its molecular mechanisms such as immunomodulation, promotion of angiogenesis, neuroprotection, and induction of antimicrobial peptides, as well as the metabolic characteristics associated with various vitamin D forms and compromised vitamin D receptor (VDR) signaling pathways. Although robust observational studies have established an association between vitamin D deficiency and adverse outcomes in DFUs, the clinical validation of supplementation efficacy through randomized controlled trials (RCTs) remains constrained by limitations such as small sample sizes, heterogeneity in study protocols, and insufficient long-term follow-up. This highlights the critical need for large-scale, high-quality studies to ascertain optimal treatment regimens and to cater to individualized patient requirements, particularly for individuals with obesity or those with renal impairments. Innovative strategies, such as the topical administration of vitamin D through intelligent delivery systems leveraging advanced biomaterials like nanofibers and hydrogels, exhibit substantial preclinical potential in enhancing stability, achieving targeted controlled release, and augmenting local biological effects, including the induction of antimicrobial peptides. Nevertheless, significant challenges persist in conclusively establishing clinical efficacy, comprehensively elucidating the underlying mechanisms, ensuring the safe translation of novel delivery systems, and developing personalized therapeutic strategies. The future success of these interventions hinges on meticulous research and interdisciplinary collaboration to seamlessly integrate validated vitamin D-based interventions into a comprehensive multidisciplinary management framework for DFUs, thereby holding promise for improving the clinical outcomes of this debilitating condition. Full article

Background: Diabetic foot ulcers (DFUs) affect 25% of diabetes patients, with high risks of amputation (70%), recurrence (65% within 3–5 years), and mortality (50–70% at 5-years). Current treatments are limited by persistent inflammation, oxidative stress, and cost barriers. This study evaluates a bioactive dressing combining a natural latex-based (NLB) biomembrane (Hevea brasiliensis) with curcumin-loaded liposomes, exhibiting angiogenic and antimicrobial properties, and red LED (light-emitting diode) phototherapy (635–640 nm) to address these challenges. Methods: A pilot clinical trial randomized 15 DFU participants into three groups: Control (CG, n = 5, standard care); Experimental Group 1 (EG1, n = 5, NLB + LED, daily treatment); and Experimental Group 2 (EG2, n = 5, NLB-curcumin liposomes + LED, daily treatment). Outcomes included wound closure, inflammatory/oxidative markers, and therapy feasibility. Assessments at D0, D22, and D45 included hematological/biochemical profiling, reactive oxygen species (ROS), and wound area measures. Results: On day 45, GE2 showed an average ulcer contraction of 89.8%, while CG showed 32.8%, and GE1 showed 9.7%. Systemic ROS and biomarkers (C-reactive protein, leukocytes) showed no significant changes (p > 0.05), though transient inflammatory spikes occurred. The combined therapy (EG2) accelerated healing without direct biomarker correlations. Conclusions: These findings highlight the potential of this combined therapy as an accessible, cost-effective DFU treatment, warranting larger studies to optimize home-based protocols and elucidate mechanisms. Full article

Diabetic foot ulcers (DFU) represent a major complication of diabetes mellitus, affecting millions of patients worldwide and leading to high morbidity and amputation risks. The impaired healing process in DFU is driven by vascular insufficiency, neuropathy, chronic inflammation, and infections. Conventional treatments, including blood sugar control, wound debridement, and standard dressings, have shown limited efficacy in achieving complete healing. Recent advancements have introduced novel therapeutic approaches such as stem cell therapy, exosome-based treatments, and bioengineered scaffolds to accelerate wound healing and tissue regeneration. Mesenchymal stem cells (MSCs), particularly adipose-derived stem cells (ASCs), exhibit anti-inflammatory, pro-angiogenic, and immunomodulatory properties, enhancing wound repair. Additionally, exosomes derived from ASCs have demonstrated the ability to promote fibroblast proliferation, regulate inflammation, and stimulate angiogenesis. The integration of bioengineered scaffolds, including hydrogels, hyaluronic acid (HA), or micro-fragmented adipose tissue (MFAT), offers improved drug delivery mechanisms and a controlled healing environment. These scaffolds have been successfully utilized to deliver stem cells, growth factors, antioxidants, anti-glycation end products, anti-inflammatory and anti-diabetic drugs, or antimicrobial agents, further improving DFU outcomes. This review highlights the potential of combining novel 3D scaffolds with anti-diabetic drugs to enhance DFU treatment, reduce amputation rates, and improve patients’ quality of life. While promising, further clinical research is required to validate these emerging therapies and optimize their clinical application. Full article

Treatment for deep diabetic foot ulcers (DFUs) and infections (DFIs) includes debridement of any dead/infected non-viable tissue, systemic antibiotics, and surgical drainage to avoid exudate stasis. Surgical drainage can cause extended incisions leading to long scars which expose these sites to ulcer recurrence and inadequate rehabilitation. In order to treat the negative impact of stasis on wound healing, we have designed an easy, minimally invasive surgical drainage technique which allows adequate ulcer cleansing by daily irrigation of any drained tract. A probe is passed along the ulcer’s infected recesses until the end and pushed against the skin, which is incised and pierced. A small 6 Fr-size silastic tube is then anchored to the probe and pulled backwards. The two ends of the tube are tied together to construct an ulcer-piercing drainage (UPD) ring. The UPD ring is designed to keep any tract open for irrigation with a syringe through both sides of the skin opening. The UPD procedure is easy and safe. The constructed blocked ring of tubing the system avoids the possibility for drainage displacement or accidental removal and can be easily utilized by any home caregiver. The UPD and irrigation are useful to provide any recess cleansing, reduce critical and negative ulcer bioburden and bacterial load, and it could avoid unnecessary and untimely extended surgical incisions leading to long uncomfortable scars, inadequate rehabilitation, relapses, or distal amputations. Full article

Photocatalysis and photodynamic therapy have been increasingly used in the management of diabetic foot ulcers (DFUs), and their integration into increasingly innovative treatment protocols enables effective infection control. Advanced techniques such as antibacterial photodynamic therapy (aPDT), liposomal photocatalytic carriers, nanoparticles, and nanomotors—used alone, in combination, or with the addition of antibiotics, lysozyme, or phage enzymes—offer promising solutions for wound treatment. These approaches are particularly effective even in the presence of comorbidities such as angiopathies, neuropathies, and immune system disorders, which are common among diabetic patients. Notably, the use of combination therapies holds great potential for addressing challenges within diabetic foot ulcers, including hypoxia, poor circulation, high glucose levels, increased oxidative stress, and rapid biofilm formation—factors that significantly hinder wound healing in diabetic patients. The integration of modern therapeutic strategies is essential for effective clinical practice, starting with halting infection progression, ensuring its effective eradication, and promoting proper tissue regeneration, especially considering that, according to the WHO, 830 million people worldwide suffer from diabetes. Full article

Background: Diabetic foot ulcers (DFUs) remain a major complication of diabetes, characterized by impaired wound healing, high infection risk, and an increased likelihood of limb amputation. Platelet-rich plasma (PRP) has emerged as a promising adjunctive therapy due to its regenerative properties, promoting angiogenesis, modulating inflammation, and accelerating tissue repair. Methods: This literature review explores the current evidence regarding the use of PRP in the management of DFUs. It was conducted using the PubMed database to evaluate the efficacy of PRP in DFUs. The search was restricted to studies published in the last 10 years, including randomized controlled trials, meta-analyses, and systematic reviews. The inclusion criteria focused on studies assessing PRP as a standalone treatment or in combination with other wound care strategies, evaluating key clinical outcomes such as wound healing rates, infection control, tissue regeneration, and amputation prevention. Results: A total of 35 studies met the inclusion criteria, including 11 meta-analyses, 15 review articles, and 9 clinical trials. PRP demonstrated potential benefits in accelerating wound healing, reducing inflammation, and promoting granulation tissue formation. Additionally, PRP combined with negative-pressure wound therapy (NPWT) showed superior outcomes in reducing amputation rates. However, findings varied based on patient characteristics, PRP preparation techniques, and treatment protocols. Conclusions: PRP represents a valuable adjunct in DFU management, contributing to improved healing outcomes and reduced complications. However, the lack of standardized protocols and variability in clinical results highlight the need for further large-scale, multicenter studies to establish its definitive role in diabetic wound care. Full article