Search Results (350)

Background/Objectives: RAPID^TM Biodynamic Haematogel is a platelet-based gel for wound healing in diabetic foot ulcers. This study aimed to identify the processing parameters that impact on the quality of this autologous point-of-care manufactured product. Methods: An innovative design of experiments (DOE) approach utilizing a split-plot factorial design and linear mixed-effects models enabled the evaluation of six processing parameters on time to gel and the exudation of gel releasate. Results: Across all manufacturing conditions, time to gel was 181.3 ± 179.2 s (n = 28) and the total mass of releasate exuded in 2 h was 5.6 ± 2.1 g (n = 28). Two processing parameters (temperature 15–30 °C and pre-mixing of ascorbic acid and L-PRP) had a significant impact on releasate exudation and/or time to gel. The other processing parameters (time-to-thrombin use, mixing time, WBC content and filtering of the thrombin) had little effect. The amount of releasate exuded was affected by the interaction of the temperature and time-to-thrombin use. Time to gel was affected by the mixing time and by pre-mixing the ascorbic acid and L-PRP in conjunction with temperature. Conclusions: This study illustrates an optimization of DOE methodology to inform pharmaceutical product development and identify factors that influence variability in the RAPID Biodynamic Haematogel product. Full article

Background: Diabetic foot syndrome is a common complication of diabetes mellitus, and its incidence is increasing due to increasing rates of overweight and an aging population. Negative pressure wound therapy has been shown to improve wound healing. This study aimed to analyze the efficacy of this therapy compared with conventional treatments in patients with diabetic foot ulcers. Methods: A systematic search was conducted in the following databases: PubMed, SCOPUS, CINAHL, and the Cochrane Library, and the methodological quality was assessed using the Rob2 scale. This meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: A total of 11 clinical trials involving 1117 subjects. The primary outcome was efficacy, which was measured by the complete healing rate, wound size, time to granulation tissue formation, adverse effects, amputations, hospital stay, and cost. This study demonstrated that this therapy improves healing (OR= −10.39, 95% CI [−14.22, −6.57]) and reduces wound size (OR = −4.11, 95% CI [−7.83, −0.39]) while potentially lowering overall costs. Conclusions: Limitations include heterogeneity and different variables measured in studies. Additionally, there were differences among the trials due to the lack of blinding. Although no significant differences were found in amputations or infections, this therapy reduces pain and decreases the use of antibiotics and analgesics. Its use requires individual and expert assessment to maximize its benefits. Full article

Diabetic foot ulcers (DFUs) are complex to heal and can lead to amputations and high healthcare costs. To address this, a promising alternative is the creation of electrospun fiber scaffolds for wound dressings. This study fabricated these scaffolds using a blend of natural polymers—chitosan (CTS), polyvinyl alcohol (PVA), and hyaluronic acid (HA)—along with antibacterial silver (Ag) and zinc oxide (ZnO) nanoparticles. The researchers conducted comprehensive analyses, including physicochemical, morphological, and biological assessments. The Ag structures showed potential as microbicidal agent, while the ZnO nanoparticles demonstrated photoactivity and the ability to generate reactive oxygen species (ROS) for antibacterial action. The resulting PVA-CTS-HA-Ag-ZnO scaffolds were found to be both hemocompatible and non-hemolytic, meaning they are safe for use with blood. The cytotoxicity evaluation using the ISO 10993-5 standard showed that the incorporation of CTS and HA decreased cytotoxicity of pure PVA, obtaining non-cytotoxic scaffolds (viability > 70%). Electrospun scaffolds composed with Ag-ZnO NPs in 50-50 and 70-30 ratios also maintained this biocompatibility, while the 30-70 ratio (Ag-ZnO) showed a cytotoxic effect, suggesting a ZnO concentration-dependent effect. These findings confirm that these materials are suitable for supporting skin cell regeneration, having a high potential for use as interactive dressings for treating chronic wounds. Full article

Introduction: Chronic wounds are a growing healthcare challenge, with infections being major complications that delay healing. Biofilms are structured microbial communities encased in extracellular polymeric substances. Biofilms confer antimicrobial resistance, promote inflammation, and protect pathogens from host defenses. These mechanisms make eradication difficult with standard therapies. Methods: A focused literature review was conducted using PubMed (2010–2025) to examine the role of biofilms in chronic wounds, diabetic foot ulcers (DFUs), and burn injuries, as well as conventional and emerging treatment strategies. Studies are included if they addressed microbial composition, host–microbe interactions, or therapeutic outcomes in clinical or translational models. Discussion: Biofilms are implicated in up to 60% of chronic wounds and more than half of burn wounds. In DFUs, both bacterial and fungal biofilms contribute to chronicity and impaired healing. Conventional treatments such as debridement and antiseptics reduce surface biofilm burden but rarely achieve full eradication. Emerging approaches include quorum sensing inhibitors, bacteriophage therapy, matrix-degrading enzymes, electroceutical dressings, antifungal strategies, and nanotechnology. They show promise when integrated with standard wound care. Conclusions: Biofilms are central to the pathogenesis of chronic wounds, DFUs, and burns. Integrating mechanism-based antibiofilm therapies with standard care represents a key research priority to improve healing outcomes. Full article

Background: Diabetic foot ulcers (DFUs) carry high risks of infection, amputation, and mortality. We systematically reviewed randomized controlled trials (RCTs) of negative-pressure wound therapy (NPWT), including single-use systems, for clinically uninfected DFUs (with sensitivity analyses for mixed/infected cohorts). Methods: We searched PubMed and Scopus (1 January 2004–30 June 2024). Dual reviewers performed screening and extraction; risk of bias was assessed with Cochrane Risk of Bias 2 (RoB 2) and certainty of evidence with GRADE. When ≥2 trials reported comparable outcomes, we used random-effects meta-analysis. The DiaFu cohort reported in two publications was counted once across analyses. Results: Eleven RCT publications (n = 1699; 10 unique cohorts) met criteria; eight trials (n = 1456) informed the primary endpoint. Trials largely excluded severe ischemia; findings therefore apply mainly to neuropathic or mixed-etiology DFUs with adequate perfusion. NPWT increased complete healing at 12–16 weeks (risk ratio [RR] 1.46, 95% CI 1.21–1.76; I² = 48%) and shortened time to healing (mean difference –18 days, 95% CI −28 to −8). Effects were similar for conventional and single-use NPWT. Outcomes did not vary systematically within commonly used pressure ranges (approximately −80 to −125 mmHg). Only two RCTs reported direct cost data (exploratory). Moderate heterogeneity (Higgins’ I² 48–68%) reflected variation in ulcer severity, device type/settings, dressing-change frequency, and off-loading protocols. Conclusions: NPWT probably improves short-term healing of clinically uninfected DFUs compared with standard care and may reduce minor amputations, without increasing adverse events. Certainty is moderate for healing and low for most secondary outcomes. Benefits appear consistent across device classes and may support earlier discharge and community-based care. Evidence gaps include ischemia-dominated ulcers, long-term outcomes (recurrence and limb preservation), adherence mechanisms, and contemporary cost-effectiveness. Full article

Diabetic foot ulcers (DFUs) and other chronic wounds are major global health challenges, often complicated by infections and delayed healing due to excessive collagen accumulation. Microbial collagenases offer an enzymatic alternative to surgical debridement by selectively degrading collagen and potentially limiting microbial colonization. In this study, an isolated and characterized thermostable collagenase from Streptomyces scabies from rhizospheric soil in Al-Lith thermal springs, Saudi Arabia, is investigated. Identification was confirmed via 16S rRNA sequencing, and enzyme production was optimized on gelatin agar. Partial purification was achieved through ammonium sulfate precipitation and dialysis, and molecular weight (~25 kDa) was determined by Sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Activity was assessed under varying temperatures, pH, substrates, and metal ions, while antibacterial potential was tested against Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The collagenase exhibited optimal activity at 80 °C and pH 9, stability under thermophilic and alkaline conditions, activation by Fe²⁺, and notable antibacterial effects at higher concentrations. These results demonstrate that S. scabies collagenase exhibits selective antibacterial activity in vitro, suggesting its potential as an enzymatic tool for further evaluation in diabetic foot debridement and infection control. Full article

Background: Irrigation is a key strategy in reducing bioburden, disrupting biofilms, and supporting wound healing. While saline is the standard for its safety and availability, antiseptic and antibiotic solutions are often used in clinical scenarios that require infection control. However, the rise in antibiotic stewardship and concerns regarding cytotoxicity are reshaping current practices. This review identifies recent trends, current controversies, and persistent gaps in knowledge that warrant further investigation and regulatory attention. Methods: A literature review identified irrigation solutions commonly used in plastic surgery; labeling and concentrations were obtained from Devices@FDA, Drugs@FDA, and DailyMed, and PubMed, Cochrane Central, and Embase were searched (January 2022–July 2025) for human studies on acute wounds, chronic wounds, and implant-based breast surgery. Results: In acute wounds, saline and potable tap water effectively prevent infection. In chronic wounds, such as diabetic foot ulcers and pressure injuries, antiseptic agents, including hypochlorous acid, sodium hypochlorite, polyhexanide, and citrate-based solutions, have shown promise in improving healing and reducing infection. In implant-based breast reconstruction and augmentation, data on antiseptics, such as chlorhexidine, and changes in FDA guidance for povidone–iodine and bacitracin have prompted a reevaluation of intraoperative irrigation practices. Conclusion: Despite widespread use, many antiseptics remain off-label, and high-quality clinical studies comparing efficacy and safety are lacking. Full article

Chronic wounds (such as diabetic foot ulcers and pressure ulcers) affect millions of patients worldwide. These non-healing wounds pose major clinical challenges due to persistent inflammation, high infection risk, and impaired tissue regeneration, and incur a substantial healthcare burden, with global wound care costs reaching tens of billions of dollars annually. This unmet need has spurred the development of intelligent wound dressings—advanced bioengineered systems that go beyond conventional passive wound coverings by actively monitoring the wound microenvironment and responding dynamically to promote tissue repair. This review comprehensively examines a broad range of smart wound dressing technologies, including pH-sensitive, temperature-responsive, moisture-responsive, pressure-sensing, electroactive, biosensor-integrated, shape-memory, and controlled drug-releasing systems. We also discuss critical challenges in translating these innovations to clinical practice, such as ensuring biocompatibility and long-term stability in the harsh wound environment, manufacturing scalability and cost-effectiveness, patient comfort and adherence, and navigating regulatory hurdles. By emphasizing recent bioengineering advances and clinical potential, we underscore that intelligent wound dressings represent a paradigm shift in chronic wound management—enabling continuous, personalized therapy with the potential to significantly improve healing outcomes, reduce complications, and improve patient quality of life. Full article

Diabetic foot ulcers drive non-traumatic lower-limb amputation; limb salvage surgery is often pursued to preserve function and survival. Predictors of adverse outcomes remain incompletely defined, and evidence for multidisciplinary team (MDT) care is heterogeneous. We aimed to clarify risk factors for major amputation and death after diabetic limb salvage and evaluate MDT impact. We systematically reviewed 49 studies (2020–2025) reporting major amputation or mortality after limb salvage in diabetes (PROSPERO CRD420251044859). Risk factors spanned demographic, clinical, and surgical domains (e.g., older age, male sex, renal/cardiovascular disease, ischemia, osteomyelitis, advanced ulcer classification). MDT models generally showed lower amputation rates and improved wound healing, with occasional survival benefits; heterogeneity precluded meta-analysis. As a real-world comparator, the Mid Essex Diabetes Amputation Reduction Plan (MEDARP) treated 72 high-risk patients using a “toe and flow” MDT. Major amputation occurred in 6.9% and mortality in 12.5%, both at or below published ranges, with gains in patient-reported outcomes. Findings support MDT-based strategies, but conclusions should be interpreted cautiously given the predominantly observational evidence, and highlight the need for standardized outcome definitions and reporting. Full article

Objective: This study aimed to systematically investigate the potential antibacterial mechanisms of ethacridine in the treatment of diabetic foot ulcers (DFUs) by integrating network pharmacology, molecular docking, and molecular dynamics simulation approaches. Methods: The potential targets of ethacridine were predicted using the SwissTargetPrediction and PharmMapper databases and subsequently converted to gene symbols via the UniProt database. DFU-related and antibacterial-related targets were retrieved from the GeneCards and OMIM databases. The overlapping targets among ethacridine, DFU, and antibacterial-related genes were identified as candidate therapeutic targets. A “drug–disease–target” network was constructed using Cytoscape, while protein–protein interaction (PPI) networks were built through the STRING database. GO and KEGG enrichment analyses were performed using R software. Molecular docking was conducted to evaluate the binding affinities between core compounds and hub targets. Furthermore, molecular dynamics (MD) simulation was applied to assess the binding stability of the top-ranked compound–target complex. Finally, RT-qPCR was conducted on wound edge tissue samples from DFU patients treated with ethacridine to experimentally validate the mRNA expression of predicted hub genes. Results: A total of 302 potential ethacridine-related targets, 4264 DFU-related targets, and 1942 antibacterial-related targets were identified. Intersection analysis revealed 105 common targets potentially involved in the antibacterial effects of ethacridine against DFU. PPI network analysis highlighted 10 hub targets, including AKT1, EGFR, SRC, HSP90AA1, and MMP9. GO enrichment indicated significant involvement in responses to reactive oxygen species, regulation of inflammatory responses, responses to lipopolysaccharide, and bacterial molecular patterns. KEGG pathway analysis identified 157 relevant pathways, including the lipid and atherosclerosis, TNF signaling, IL-17 signaling, and the AGE–RAGE signaling pathways in diabetic complications. Molecular docking demonstrated favorable binding affinities (all < −5.0 kcal/mol) between ethacridine and the hub targets, with the strongest binding observed between MMP9 and ethacridine (−9.8 kcal/mol). These docking results suggest possible interaction tendencies that may contribute indirectly to Ethacridine’s network-level regulatory effects, rather than direct binding to all targets in vivo. Molecular dynamics simulation further confirmed the stable interaction between MMP9 and ethacridine. RT-qPCR validation in clinical DFU tissue samples demonstrated expression trends of key genes consistent with in silico predictions. These results reflect transcriptional regulation consistent with pathway modulation predicted by the network analysis, rather than direct protein–ligand binding across all targets. Conclusion: Ethacridine may exert antibacterial effects against bacterial biofilms in DFU through multi-target and multi-pathway mechanisms. These findings highlight ethacridine’s translational potential as a safe, readily available, and mechanistically validated topical agent for the clinical management of biofilm-associated diabetic foot infections. Full article

Background: Diabetes-related foot diseases represent a global health problem because of the associated complications, the risk of amputation, and the economic burden on health systems. Negative pressure wound therapy (NPWT) is a technique that uses sub-atmospheric pressure to help promote wound healing by reducing the inflammatory exudate while keeping the wound moist, inhibiting bacterial growth, and promoting the formation of granulation tissue. Objective: This study aimed to assess the effectiveness of NPWT in preventing major amputation in diabetic patients with complicated foot or lower limb infections and to contextualize the results through a review of the existing literature. Materials and methods: We conducted a retrospective study at the First Surgical Department of “Dr. I. Cantacuzino” Clinical Hospital in Bucharest, Romania, over a 15-year period, including 30 consecutive adult patients with diabetes and soft tissue foot or lower limb infections treated with NPWT. Patients with non-diabetic ulcers, incomplete medical data, or aged under 18 were excluded. All patients underwent initial surgical debridement, minor amputation, or drainage procedures, followed by the application of NPWT using a standard protocol. Dressings were changed every 2–4 days for a total of 7–10 days. Antibiotic therapy was adapted according to the culture results. The primary outcome was limb preservation, defined as avoidance of major amputation. Secondary outcomes included in-hospital mortality and wound status at discharge. Results: NPWT was associated with a favorable outcome in 24 patients (80%), defined by wound granulation or healing without the need for major amputation. Five patients (16.6%) underwent major amputation because of failure of the primary lesion treatment, and one patient died. No statistically significant association was observed between the outcomes and standard classification scores (WIFI, IWGDF, and TPI). A comprehensive literature review helped to integrate these findings into the existing pool of knowledge. Conclusions: NPWT may support limb preservation in selected diabetic foot cases. While the retrospective design and the small sample size of the study limit generalizability, these results reinforce the need for further controlled studies to evaluate NPWT in real-life clinical settings. The correct use of NPWT combined with etiological treatment may offer a maximum chance to avoid major amputation in patients with diabetes-related foot diseases. Full article

Diabetic foot infections (DFIs) are a significant complication in patients with diabetes, often leading to severe clinical complications including amputation and increased mortality rates. The effective management of these infections is complicated by the rise in antibiotic resistance among the microbial populations involved. In this paper, we undertake a systematic review and meta-analysis to explore the bacterial profiles, as well as their antibiotic resistance patterns in DFIs, encompassing studies published between 2014 and 2024. A total of 28 studies were selected from several databases, including PubMed, Google Scholar, EBSCOhost, and ScienceDirect, published from 2014 to 2024, specifically focusing on diabetic foot infections and antibiotic resistance. Diabetic foot infections arise from a combination of factors, including peripheral neuropathy, poor circulation, and immune system impairment, making diabetic patients prone to unnoticed injuries, impaired wound healing, and a higher risk of infections. The severity of DFIs often depends on the size and depth of the ulcers, with larger, deeper ulcers posing additional risks of infection and complications, such as osteomyelitis and sepsis. Our study synthesizes information on the total isolates of microbes, their resistance to one or more groups of antibiotics, and resistance panel results across multiple antibiotics, including amoxicillin/clavulanate, trimethoprim/sulfamethoxazole, ciprofloxacin, and others. We meticulously catalog the resistance of key bacterial strains—Escherichia coli, Enterobacter spp., Proteus spp., Pseudomonas spp., Staphylococcus aureus, and others—highlighting patterns of resistance to single and multiple antibiotic groups. This systematic review also analyzes the correlations of various comorbidities reported by the diabetic foot infection patient populations in the included studies with multiple antibiotic resistance patterns. Subsequently, this analytical review study addresses the rising prevalence of antibiotic-resistant pathogens and underscores the need for antibiotic stewardship programs to promote judicious use of antibiotics, reduce the spread of resistant strains, and enhance therapeutic outcomes. In addition, the review discusses the implications of resistance to empirical antibiotic treatments, underscoring the necessity for tailored antibiotic therapy based on culture and sensitivity results to optimize treatment outcomes. Full article

Diabetic wounds, especially diabetic foot ulcers, pose a major global clinical challenge due to their slow healing and high infection susceptibility. Their typical pathological features include impaired angiogenesis, chronic hypoxia, persistent inflammation, oxidative stress, bacterial colonization, and neuropathy. Traditional treatment methods have limited efficacy, creating an urgent need for innovative therapeutic strategies. In recent years, biomaterials have emerged as a research focus in diabetic wound treatment, owing to their biocompatibility, versatility, and tissue regeneration potential. This article comprehensively reviews the pathological mechanisms of diabetic wounds. It also summarizes the application progress of biomaterials in diabetic wound healing. Over the past decade, researchers have explored the properties, mechanisms of action, and roles of various natural and synthetic biomaterials. These biomaterials include DNA nanomaterials, peptide hydrogels, cells, exosomes, and cytokines. These biomaterials play significant role in promoting angiogenesis, regulating inflammation, inhibiting bacteria, and enhancing cell proliferation and migration. Full article

Introduction: This study will explore the effectiveness of current extracorporeal shockwave therapies in ulcer healing in diabetic foot disease compared to the standard of care. Methods: The systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. The electronic databases WoS, EMBASE, MEDLINE Complete, CINAHL Complete, Academic Search Ultimate, AMED-The Allied and Complementary Medicine Database, Scopus and PubMed searched for the outcome rate of complete ulcer healing. The risk of bias assessment was conducted using the tool recommended by the Cochrane Collaboration (Robvis Tool). Statistical analysis included the individual and combined result of the studies, heterogeneity test, the effect size, sensitivity analysis, and publication bias tests. Results: Eight randomized controlled trials (RCTs) with a total of 672 patients were included in this study. This meta-analysis showed a higher rate of complete ulcer healing in groups receiving extracorporeal shockwave therapies (OR = 2.747 [1.965, 3.841], p < 0.01, I² =0.02) compared to control groups. Conclusions: In conclusion, the results of this meta-analysis show that extracorporeal shockwave therapies, when used as an adjunctive treatment, demonstrate significantly higher ulcer healing rates compared to standard of care. Extracorporeal shockwave therapies should be taken into account as a valuable adjunct to standard care for diabetic foot ulcer treatment. Full article

Background: Diabetes mellitus is a heterogeneous chronic disease with an increasing global prevalence. In Romania, 11.6% of the population is affected, yet only 6.46% receive treatment. Among diabetic patients, 15–25% develop skin lesions that may progress to ulceration and necrosis, significantly impairing quality of life and increasing the risk of complications. Methods: We conducted a prospective study including 28 patients (14 in the control group and 14 in the intervention group) with type I or II diabetes and chronic ulcers of the calf or foot (>4 cm²). The control group received standard therapy with debridement, dressings, antibiotics when indicated, and local and systemic ozone therapy. The intervention group was treated with an Integrative Therapeutic Protocol combining ozone therapy, pulsed electromagnetic field therapy (PEMF), colon hydrotherapy with probiotic supplementation, and an anti-inflammatory alkaline diet. Wound healing (reduction in ulcer surface area) was the primary endpoint; secondary endpoints included changes in glycemia and inflammatory biomarkers. Results: After 8 weeks, the intervention group achieved 86.2% re-epithelialization versus 58.2% in controls (p < 0.01). Significant improvements were also observed in blood glucose level (−38%), HbA1c (−25%), CRP (−26%), and fibrinogen (−28%) relative to baseline, with differences versus controls reaching statistical significance. Conclusions: The Integrative Therapeutic Protocol accelerated wound healing and improved glycemic and inflammatory profiles compared with ozone therapy alone. Although an alkaline diet was recommended, adherence and its specific contribution were not objectively monitored; therefore, this component should be interpreted with caution. Full article