Treatment Of Diabetic Foot Ulcers Research Articles

Deep Red Light Driven Hydrogen Evolution by Heterojunction Polymer Dots for Diabetic Wound Healing.

We describe small heterojunction polymer dots (Pdots) with deep-red light catalyzed H2 generation for diabetic skin wound healing. The Pdots with donor/acceptor heterojunctions showed remarkably enhanced photocatalytic activity as compared to the donor or acceptor nanoparticles alone. We encapsulate the Pdots and ascorbic acid into liposomes to form Lipo-Pdots nanoreactors, which selectively scavenge •OH radicals in live cells and tissues under 650 nm light illumination. The antioxidant capacity of the heterojunction Pdots is ~10 times higher than that of the single-component Pdots described previously. Under a total light dose of 360 J/cm2, the Lipo-Pdots nanoreactors effectively scavenged •OH radicals and suppressed the expression of pro-inflammatory cytokines in skin tissues, thereby accelerating the healing of skin wounds in diabetic mice. This study provides a feasible solution for safe and effective treatment of diabetic foot ulcers.

Efficacy and safety of ultrasound-assisted wound debridement in the treatment of diabetic foot ulcers: a systematic review and meta-analysis of 11 randomized controlled trials

ObjectiveResearch data suggests that ultrasound-assisted wound debridement (UAWD) can effectively promote the healing of diabetic foot ulcers (DFU). However, existing research is not consistent with this viewpoint. Therefore, we conducted this study to investigate the effect of UAWD on the healing of diabetic foot ulcers.MethodsFrom the establishment of the database to January 2024, we searched 8 databases to study the effectiveness and safety of UAWD in the treatment of DFU. Two authors independently screened the qualifications of the articles, while two authors extracted relevant data. Statistical analysis was conducted using Review Manager 5.4 and STATA 18.0 software.ResultsA total of 11 randomized controlled studies were included, with 6 countries and 696 participants participating. Our findings showed that UAWD was associated with a significant benefit in healing rate (OR = 2.60, 95% CI: [1.67, 4.03], P < 0.0001, I2 = 25%), wound healing time (MD = -11.94, 95% CI: [-23.65, -0.23], P = 0.05, I2 = 99%), percentage reduction in wound size (MD = 14.2, 95% CI: [10.8, 17.6], P = 0.47, I2 = 32%), effectiveness of treatment (OR = 10.3, 95% CI: [4.68, 22.66], P < 0.00001, I2 = 0%). Moreover, UAWD did not cause any significant adverse reactions. However, there was no obvious difference in wound blood perfusion (MD = 0.25, 95% CI: [-0.01, 0.52], P = 0.06, I2 = 90%), transcutaneous oxygen partial pressure (MD = 14.34, 95% CI: [-10.03, 38.71], P = 0.25, I2 = 98%).ConclusionUAWD can significantly improve wound healing rate, shorten wound healing time, accelerate wound area reduction, and improve clinical treatment effectiveness without significant adverse reactions. Although there is no significant difference in transcutaneous oxygen pressure and wound blood flow perfusion between UAWD and SWC. So we look forward to more scientifically blinded, placebo-controlled, high-quality studies in the future, to enable researchers to obtain more complete and accurate analytical data, in order to improve the scientific and credibility of the evidence.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024501198.

Combining antibiotic-loaded bone cement-based free vastus lateralis muscle-sparing flap with split-thickness skin grafts: A reliable strategy for reconstructing diabetic foot ulcers at non-weight-bearing areas.

Diabetic foot ulcers (DFUs) present significant challenges due to their associated amputation rates, mortality, treatment complexity and excessive costs. Our earlier work introduced a wound surgical integrated treatment (WSIT) for DFUs, yielding promising outcomes. This study focuses on a specific WSIT protocol employing antibiotic-loaded bone cement (ALBC) in the first Stage, and free vastus lateralis muscle-sparing (VLMS) flaps and split-thickness skin grafts (STSGs) in the second stage to repair non-weight-bearing DFUs. From July 2021 to July 2023, seven DFU patients (aged 47-71 years) underwent this treatment. Demographic data, hospital stay and repair surgery times were collected. Histological and immunohistochemical analyses assessed angiogenesis, collagen deposition and inflammation. SF-36 questionnaire measured pre- and postoperative quality of life. Preoperative ultrasound Doppler showed that the peak blood flow velocity of the recipient area artery was significantly >30 cm/s (38.6 ± 6.8 cm/s) in all patients. Muscle flap sizes varied from 8 × 3.5 × 1 to 18 × 6 × 2 cm. The operation time of the repair surgery was 156.9 ± 15.08 minutes, and the hospital stay was 18.9 ± 3.3 days. Histological analysis proved that covering DFUs with ALBC induced membrane formation and increased collagen, neovascularization and M2 macrophages fraction while reducing M1 macrophages one. All grafts survived without amputation during a 7- to 24-month follow-up, during which SF-36 scores significantly improved. A combination of ALBC with free VLMS flaps and STSGs proved to be safe and effective for reconstructing non-weight-bearing DFUs. It rapidly controlled infection, enhanced life quality and foot function, and reduced hospitalization time. We advocate integrating this strategy into DFU treatment plans.

An innovative support pillow for diabetic foot wound care

Background: Treating diabetic foot ulcers (DFU) sometimes takes a long time. During treatment, the patient's feet are usually given a cushion (such as a sleeping pillow or bolster) to make the wound seen. This way, some patients reported that their feet tingled because they were not positioned rightly for an extended period. So far, no unique pillow is available for this function. This pillow would help in treating DFU and should be comfortable for patients. Thus, it is essential to research designing such a product.Purpose: To develop and test a special pillow for treating DFU.Methods: This research adopts Research and Development (R&D). This research is divided into two stages: designing and developing and product testing.Results: This pillow is made of multiplex and foam, covered with Polyester fabric. It is 75mm in length and 45mm in width. It is equipped with a foot care area and waste storage tank. The test results showed that the score for comfort for the patients was 92%, while the score from the nurse was 88%.Conclusion:The pillow product helps the nurse conduct the DFU treatment and is comfortable for the patients. 

Homogenized and Lyophilized Amniotic Membrane Dressings for the Treatment of Diabetic Foot Ulcers in Ambulatory Patients.

Diabetic foot ulcers (DFUs) constitute a complication that occurs in 19% to 34% of patients with diabetes mellitus (DM). The aim of this study is to describe median days to healing, average velocity of wound closure, and percentage of wound surface closed at 3, 6, and 12 weeks through the use of homogenized and lyophilized amniotic membrane (hAMpe) dressings for the treatment of DFUs in ambulatory patients. An observational, descriptive, longitudinal study was performed. Patients presenting with granulation-based DFU, after proper debridement, were included from August 19, 2021, until July 14, 2023. hAMpe dressings placed every 3 days were used for the treatment of these ulcers. Sixteen patients were included with a mean age of 52.38 (8.07) years. The analyzed lesions were postsurgical ulcers in 15 of the 16 included patients. Median ulcer size was 19.5 cm2 (6.12-36). The median ABI was 1.10 (1-1.14). The median days to healing was 96 (71-170). The median percentage closure of the wound at 3 weeks was 41% (28.9%-55.3%), at 6 weeks it was 68.2% (48.6%-74.2%), and at 12 weeks it was 100% (81%-100%). The average velocity closure was 1.04% per day (95% CI 0.71%-1.31%). It was higher during the closure of the first 50% of the ulcer, 2.12% per day (95% CI 0.16%-4.09%), and decreased from 50% to 25% of the ulcer size to 0.67% per day (95% CI 0.23%-1.10%) and from 25% to closure to 0.47% per day (95% CI 0.14%-0.80%), P < .001. These results are difficult to compare to other studies given the higher surface area of the ulcers included in our sample. The development of hAMpe dressings enables patients to apply them without requiring assistance from health care teams and was not associated with any recognized complications. Level IV, case series.

Exploring the efficacy of photodynamic antimicrobial chemotherapy on diabetic foot ulcers in rats.

We investigate the efficacy of photodynamic antimicrobial chemotherapy (PACT) and its combination with an antibiotic in the treatment of diabetic foot ulcers (DFUs) in rats using a novel cationic amino acid porphyrin-based photosensitizer. The research findings demonstrate that the combination of novel cationic photosensitizer-mediated PACT and an antibiotic exhibits significant therapeutic efficacy in treating deep ulcers in a rat model of DFUs. Moreover, the PACT + Antibiotic group displays enhanced angiogenesis, improved tissue maturation, and superior wound healing effect. Micro-computed tomography examination showed that the periosteal reaction was most obvious in the PACT + Antibiotic group. The cortical bone volume ratio (BV/TV), the bone mineral density, and trabecular thickness were significantly higher in the PACT + Antibiotic group than in the model group (p < 0.05). The combination of PACT and antibiotic plays a sensitizing therapeutic role, which provides a new idea for the clinical treatment of DFUs.

Foam dressing and micropower vacuum dressing promote diabetic foot ulcer wound healing by activating the PI3K/AKT/mTOR pathway in rats.

Foam dressing (FD) and micropower vacuum dressing (MVD) have been applied in the treatment of diabetic foot ulcer (DFU). However, research about the mode of action on the efficacy of the two dressings is extremely rare. This study proposed to explore the mechanism involved in diabetic wound healing under FD or MVD treatment. Macroscopical study was performed to evaluate the effectiveness of FD and MVD on wound healing in a rat model of DFU. Morphological analysis in the wound skin tissue was conducted by hematoxylin and eosin staining. Meanwhile, inflammatory cytokines in serum were measured by enzyme linked immunosorbent assay. The protein expression of phosphatidylinositol 3 kinase, protein kinase B and mammalian target of rapamycin (PI3K/AKT/mTOR) and their phosphorylation levels were determined by western blotting. We found that wound healing in rats with DFU was enhanced with the application of FD and MVD. The therapeutic efficacy of FD was superior to MVD. Compared with diabetic foot group, the concentrations of inflammatory cytokines, tumor necrosis factor alpha, interleukin-1β and interleukin-6, were significantly down-regulated. Besides, the phosphorylation levels of PI3K, AKT and mTOR were up-regulated under FD or MVD treatment. We demonstrated that the treatment of FD and MVD effectively promoted the wound skin healing through activating the PI3K/AKT/mTOR pathway. Our research may provide a new idea for exploring the mode of action of dressing application in healing of DFU.

PROS1 is a crucial gene in the macrophage efferocytosis of diabetic foot ulcers: a concerted analytical approach through the prisms of computer analysis.

Diabetic foot ulcers (DFUs) pose a serious long-term threat because of elevated mortality and disability risks. Research on its biomarkers is still, however, very limited. In this paper, we have effectively identified biomarkers linked with macrophage excretion in diabetic foot ulcers through the application of bioinformatics and machine learning methodologies. These findings were subsequently validated using external datasets and animal experiments. Such discoveries are anticipated to offer novel insights and approaches for the early diagnosis and treatment of DFU. In this work, we used the Gene Expression Omnibus (GEO) database's datasets GSE68183 and GSE80178 as the training dataset to build a gene model using machine learning methods. After that, we used the training and validation sets to validate the model (GSE134431). On the model genes, we performed enrichment analysis using both gene set variant analysis (GSVA) and gene set enrichment analysis (GSEA). Additionally, the model genes were subjected to immunological association and immune function analyses. In this study, PROS1 was identified as a potential key target associated with macrophage efflux in DFU by machine learning and bioinformatics approaches. Subsequently, the key biomarker status of PROS1 in DFU was also confirmed by external datasets. In addition, PROS1 also plays a key role in macrophage exudation in DFU. This gene may be associated with macrophage M1, CD4 memory T cells, naïve B cells, and macrophage M2, and affects IL-17, Rap1, hedgehog, and JAK-STAT signaling pathways. PROS1 was identified and validated as a biomarker for DFU. This finding has the potential to provide a target for macrophage clearance of DFU.

Using 3D Bioprinted Autologous Minimally Manipulated Homologous Adipose Tissue for Limb Salvage in Treating Diabetic Foot Ulcer

AbstractReconstructive surgeons face challenges when considering limb salvage methods for the treatment of diabetic foot ulcers (DFUs). In this article, we present our experience with autologous fat grafting as a viable alternative in cases where flap reconstruction is difficult. We encountered a 78-year-old female patient with a nonhealing DFU who had multiple comorbidities, including renal failure and severe peripheral arterial disease. During the initial multidisciplinary meeting, due to extensive necrosis and osteomyelitis, amputation was recommended. However, the patient expressed a strong preference for a salvage procedure and refused amputation. After careful consideration, we opted to reconstruct the patient's foot using three-dimensional bioprinted autologous minimally manipulated homologous adipose tissue. The AMHAT was engrafted well without complications such as autolysis, graft failure, or infection. After the operation, the large defect with partial bone exposure was covered with healthy granulation tissue. The size of the wound decreased to less than half its original size after 6 weeks of surgery, and it decreased to less than 25% after 12 weeks of surgery. The AMHAT may be an appealing treatment option for diabetic foot patients who are unsuitable for flap reconstruction due to comorbidities.

A Case of a Patient with Combined Diabetic Peripheral Neuropathy and Peripheral Vasculopathy Who Achieved Healing After Combined Multidisciplinary Outpatient Treatment of the Diabetic Foot

Diabetic foot ulcer is one of the serious complications of diabetes, which is a chronic wound caused by a combination of factors such as limb ischemia, infection, lower limb neuropathy, etc. Its treatment and wound management pose significant challenges to all healthcare professionals. Currently, treatment for diabetic foot ulcers often focuses on surgical interventions such as skin grafting and amputation, significantly impacting patients’ quality of life. A 61-year-old female patient presented to the clinic due to a swollen skin breakdown on the right inner ankle. She was diagnosed with diabetes at the age of 53 and developed her first diabetic foot ulcer at the age of 60. Laboratory results from this visit revealed a glycosylated hemoglobin level of 9.7%, a glycosylated albumin level of 26.8% and a fasting blood glucose level of 16.1 mmol/L. Ultrasonography of the lower limb arteries showed localized intimal-medial thickening with multiple sclerotic plaque formation on both lower limbs. For this patient, the multidisciplinary joint outpatient clinic for the diabetic foot was given systemic treatments such as blood glucose control, nerve nourishment, circulation improvement, lipid regulation and plaque fixation, while the diabetic foot care specialist gave an individualized wound treatment plan of cleansing, debridement and dressing coverage by evaluating the wound’s pH, infection grading and exudate traits, among other indicators. After 2 months of comprehensive treatment, the patient’s blood glucose control was stable and the ulcer healed. This case of recurrent ulcer rehabilitation provides new ideas for diabetic foot ulcer wound treatment and individualized wound treatment based on diabetic foot care led by experts holds promise as another effective means for healing diabetic foot ulcers.

Role of Vacuum Assisted Closure Therapy Compared to Standard Moist Wound Dressing in the Treatment of Diabetic Foot Ulcers.

Role of Vacuum Assisted Closure Therapy Compared to Standard Moist Wound Dressing in the Treatment of Diabetic Foot Ulcers.

A Novel Potential Treatment for Diabetic Foot Ulcers and Non-Healing Ulcers - Case Series.

Appropriate care and treatment of a wound is the need of the hour whether it is an infected or a non-infected wound. If wound healing is delayed for some reason, it leads to serious complications and further increases the hospital stay and cost of treatment. Herein, we describe a novel antimicrobial wound dressing formulation (VG111), with an objective to generate the preliminary data showing the distinct advantages in various types of wounds. This case series involved the treatment of acute cases of wounds or chronic wounds that did not respond well to conventional wound healing treatments with VG111 in patients with different etiologies. Thirteen cases of patients that included patients with diabetes, pressure ulcers, burns, trauma, and others treated with VG111 showed rapid wound healing in all the cases even obviating the need for a graft when complete skin regeneration occurred. This was illustrated by clearing of the wound infections, reduction/disappearance of the exudate, appearance of intense granulation, epithelialization, and anti-biofilm activity followed by complete wound closure. This VG111 precludes the need for systemic antimicrobial agents in localized infections and therefore, this single agent is an attempt to address the limitations and the drawbacks of the available products. Despite patients belonging to the old age group and having comorbidities like diabetes, still VG111 showed effective rapid wound healing, and that too without any scar formation in hardto- heal, infected, and non-infected wounds.

Thermo-responsive microneedles patch for transdermal drug delivery via squeezing in diabetic foot ulcers

Microneedles (MNs) patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide. While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches, it can create toxic chemical residues or require the help of additional devices. Herein, a thermo-responsive microneedles patch (TMN) with high biocompatibility without additional equipment is proposed. The TMN consisted of a bilayer microneedles composed of sodium alginate (SA)-g-poly(N-isopropylacrylamide) layer (SA-g-PNIPAM) loaded with sucrose octasulfate sodium salt (SOS) and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride (TH) and SOS. PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes, and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation. The results showed that the drug release of TMN was significantly faster, with a drug release rate of more than 80% in the 10th h, and the antibacterial rate of TMN could reach 800%. In addition, TMN had good biocompatibility and good healing effects in vivo, which may be helpful for the design of multifunctional dressings in the future.

Potassium permanganate in treatment of diabetic foot ulcer: A randomized clinical trial.

Diabetic foot ulcers (DFU) are a severe complication in diabetes patients, often resulting in significant morbidity and mortality due to non-healing. This study investigated the effectiveness of 5% topical potassium permanganate on these ulcers. A clinical trial was conducted on 23 patients with Wagner grade I and II DFU. Patients in the control group received standard treatment, while those in the intervention group also received 5% potassium permanganate topically. Data were recorded at 0, 7, 14, and 21 days for analysis. Among 23 patients studied, 7 (30.4%) were male and 16 (43.7%) female, with an average age of 59 ± 4 years. Both groups showed a statistically significant decrease in wound size and infection over time (p < 0.001). The intervention group, however, had a more substantial reduction in wound size and infection rate (p < 0.05). Potassium permanganate, when applied topically, is both well-tolerated and effective in enhancing wound healing and reducing infection in DFU, suggesting its potential as a complementary treatment.

Multi-target mechanism of polyherbal extract to treat diabetic foot ulcer based on network pharmacology and molecular docking

Introduction: Diabetic foot ulcer (DFU) potentially leads to loss of function, infections, hospitalization, lower-extremity amputation, and even death. The potential therapeutic efficacy of a polyherbal candidate named TIP-Heal was identified for treating DFU. TIP-Heal, which stands for Tinospora crispa, Isotoma longiflora, and Piper betle L var nigra, consists of extracts from these three herbs in a ratio of 2:1:1. The Indonesian population commonly uses these herbs due to their wound-healing properties. It is our interest to analyse the mechanism of the polyherbal extract using network pharmacology and molecular docking. Methods: This study uses network pharmacology and molecular docking methods to analyze the multi-target mechanism of active compounds in TIP-Heal extract for DFU treatment. The proteins targeted by the bioactive chemical present in TIP-Heal and DFU were identified within a particular dataset with the keyword "homo sapiens." The identified target proteins were assessed using gene ontology (GO) analysis, the Kyoto Encyclopaedia of Gene and Genomes (KEGG) pathways, protein-protein interactions (PPIs), and molecular docking. Results: The critical proteins obtained were AKT serine/threonine kinase 1 (AKT1), caspase-3 (CASP3), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and matrix metalloproteinase-9 (MMP-9). Several compounds, namely PubChem (Compound Identifier=CID: 5319898), 3-epiursolic acid, palmitic acid, and alpha-linolenic acid showed great potential as viable candidates to facilitate the healing process of DFU. Conclusion: The findings of this study indicate that the TIP-Heal extract has the potential to be used as a natural herbal treatment for DFUs with the involvement of AKT1, CASP3, EFGR, and SRC proteins.

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Diagnosis, Treatment, Prevention, and Rehabilitation of Diabetic Foot Ulcers and Infections: Turkish Consensus Report, 2024

Diagnosis, Treatment, Prevention, and Rehabilitation of Diabetic Foot Ulcers and Infections: Turkish Consensus Report, 2024

Analysing patient factors and treatment impact on diabetic foot ulcers in South Africa

In the South African public healthcare sector, 28% of diabetic patients present to primary healthcare clinics with diabetic foot ulcers (DFUs), often presenting in advanced stages of ulcer severity. In this study, we aimed to categorise factors predisposing individuals to developing a DFU and to identify the potential shortcomings in existing treatment plans in the South African healthcare system. In addition, the use of preventative measures in the management of DFUs was examined as well as the influence of past treatment practices. A total minimum sample size of 50 DFUs was required for this study. Participants who were selected for this study had their past records reviewed in order to determine the likelihood of previous DFU infections, as well as to determine the occurrence of co-morbidities. The treatment protocol implemented was recorded. Twelve-month patient records were used to identify the infection frequency and past treatment protocols. A total of 48.9% of patients reported that they did not make use of any preventative measures. The most frequent concurrent medical conditions were hypertension, dyslipidaemia, and peripheral neuropathy. Polypharmacy was prevalent, with 55% of the population prescribed five or more medications. Potential medication interactions were examined and a total of 210 interactions were documented. An analysis of past and current treatment practices revealed that 52.1% of the treatment protocols did not comply with local treatment guidelines. This study highlights the urgent need for updated DFU treatment protocols in relation to the overall management of DFUs, taking into account existing international guidelines.

[National expert consensus on the diagnosis and surgical treatment of diabetic foot ulcers complicated with lower extremity vasculopathy (2024 version)].

Diabetic foot ulcers complicated with lower extremity vasculopathy possess the characteristics of high incidence, slow healing, and poor prognosis, which may eventually lead to amputation or even life-threatening if not treated properly. The treatment of complicated lower extremity vasculopathy is vital to improve the healing process of diabetic foot ulcers, which has gradually received attention in clinical practice. Recently, a number of clinical trials on diabetic foot ulcers complicated with lower extremity vasculopathy were reported. In order to further standardize the clinical diagnosis and treatment of diabetic foot ulcers complicated with lower extremity vasculopathy, an expert group headed by Burns and Trauma Branch of Chinese Geriatrics Society, Chinese Burn Association, and Wound Repair Professional Committee of Chinese Medical Doctor Association deliberated and compiled the National expert consensus on the diagnosis and surgical treatment of diabetic foot ulcers complicated with lower extremity vasculopathy (2024 version) together. This consensus is based on evidences from the literature, covers the disease characteristics, evidence-based evidence of clinical diagnosis and treatment, as well as the application of new technologies and new treatment approaches of diabetic foot ulcers complicated with lower extremity vasculopathy. The goal of this consensus is to provide clear guidance to practitioners on the best approaches for screening, diagnosing, and treating diabetic foot ulcers complicated with lower extremity vasculopathy in individuals, hoping to provide a normative clinical practice basis for medical staff engaged in the treatment of diabetic foot wounds.

Evaluating a promising methylcellulose hydrogel for enhanced diabetic foot ulcer therapy through comprehensive preclinical studies

The present research focuses on formulating and evaluating hydrogels modified with crosslinking agents using methylcellulose to treat diabetic foot ulcers (DFU). Methylcellulose hydrogels are prepared and characterized for their crosslinking capacity through FTIR and degradation studies. The optimized hydrogel is further assessed for viscosity, gel strength, contact angle, in-vitro biodegradation, water-vapor transmission rate, anti-bacterial activity, and in-vivo efficacy. The results demonstrate that the developed hydrogel exhibits promising properties for DFU treatment, including increased wound healing percentage, improved ulcer morphology, reduced levels of proinflammatory cytokines, and enhanced tissue characteristics. These findings suggest that the novel hydrogel composition could serve as a viable alternative to existing dressings for DFU management.