Wound Healing In Diabetic Ulcers Research Articles

Drug Interactions in Diabetic Ulcer Patients in an Indonesian Private Hospital

Diabetic ulcers can progress into tissue death, or gangrene, which create a risk for amputation. Measures for preventing other complications and accelerating wound healing in diabetic ulcers include blood sugar level control, diet adjustment, wound care, antidiabetic drug administration, and comorbid therapy. This leads to the use of various drugs that can potentially trigger drug interactions. This study aimed to identify possible drug interactions in the therapeutic management of diabetic ulcer patients treated in Husada Utama Hospital Surabaya, Indonesia, from January 2020–June 2022. This was a descriptive observational study using retrospective data from medical records. Results showed that 103 types of drugs were administered to 48 research samples with 41 of them experienced drug interactions (n=263 cases). Based on the severity of drug interactions, 31 cases were categorized as major cases (11.79%), with drug-class antibiotic-antiemetic interactions as the most frequent interactions. This study proves that it is essential for doctors and pharmacists.

RECOMBINANT HUMAN EPIDERMAL GROWTH FACTOR IN TREATING DIABETIC FOOT ULCERS-A RANDOMISED CONTROLLED TRIAL

Background: Diabetic foot ulcers are among the most common complications in patients with poor glycemic control. Diabetic foot ulcers are the result of poor glycemic control, underlying neuropathy, peripheral vascular disease, or poor foot care. Diabetic foot ulcers are a debilitating complication of diabetes mellitus that leads to increased overall morbidity in patients. When the recombinant human epidermal growth factor (rhEGF) is used as the topical application it stimulates epithelial proliferation, differentiation, and migration. As a result of this, there is an acceleration of epithelial regeneration and wound healing of diabetic ulcers. The Aim and Objective: aim is to study the efcacy of recombinant human epidermal growth factor by comparing the time taken for healing, cost-effectiveness, patient compliance, and duration of hospital stay after topical application of epidermal growth factor over a control group treated with conventional dressings of saline and hydrogen peroxide, which acts as the control group. This study is a randomized controlled trial conducted in the Methods: Department of General Surgery, Kanyakumari Government Medical College, from September 2022 to February 2023. A total of 60 patients were divided into two groups: 30 patients in the interventional group treated with rhEGF and 30 patients in the control group receiving conventional dressings with saline and hydrogen peroxide were monitored, and the wound healing time, patient compliance, cost effectiveness, and duration of hospital stay were studied. A total of Results: 60 patients of which 38 (63.3%) were males and 22(36.6%) were female patients. The wound healing was better in the group treated with rhEGF and the duration of hospital stay was signicantly shorter. Patient compliance was found to be similar in both groups & conventional wound dressing was found to be cost effective as rhEGF topical application is a costly affair. This study suggests that recombinant human Conclusion: epidermal growth factor helps in the acceleration of epithelial regeneration and wound healing in diabetic ulcers. Patients who were treated with recombinant human epidermal growth factor had a signicant reduction in wound healing time and decreased duration of hospital stay.

Exploring Metformin as the Potential Oral Antidiabetic of Choice for Type II Diabetes Mellitus with Wound Comorbid: A Case-based Literature Review

Diabetes is a metabolic disease characterized by hyperglycemia caused by a disruption in insulin secretion, insulin function, or both. An individual with diabetes have a greater likelihood to develop chronic non-healing wounds, and if untreated, various chronic complications are associated with psychiatric stress and depression. In diabetic wounds, the inflammatory phase becomes persistent and excessive with impaired cell proliferation and greater risk of infection. Several studies have shown that metformin has potential effect for diabetic wound healing. Here, we reported a case of diabetic wound in East Jangkat, a rural area in Indonesia, with premorbid type 2 diabetes mellitus and obesity class II with a deeper discussion about the potential effect of metformin for wound healing in diabetic ulcers.

Effects of Intensive Glycemic Control on Serum Exosome miR-126-3p and miR-125b-1-3p Levels and Wound Healing in Patients with Diabetic Ulcers.

Intensive glycemic control and exosomal miRNAs have both been reported to improve wound repair in diabetic ulcers. In this study, we aimed to investigate the effects of intensive glycemic control on serum exosome microRNA-126-3p (miR-126-3p), microRNA-125b-1-3p (miR-125b-1-3p), and wound healing in patients with diabetic ulcers. Herein, 45 diabetic patients with an ulcer, aged 35-75 years old, were randomly assigned to the intensive glycemic control group (n = 21) and the conventional glycemic control group (n = 24). Serum exosomes were extracted in the laboratory and assessed by Western blotting, transmission electron microscopy, and nanoparticle tracking analysis. The expression of miR-126-3p and miR-125b-1-3p was validated using quantitative real-time polymerase chain reaction. The wound healing of each diabetic ulcer patient was measured and imaged; additionally, clinical and follow-up data were collected. Finally, the clinical and laboratory data were combined for statistical analysis. Intensive glycemic control was significantly more conducive to wound healing and infection control than conventional glycemic control (P < 0.05). Serum exosomal miR-126-3p was negatively correlated with fasting plasma glucose levels (r = 0.34, P < 0.05) and positively associated with the wound healing rate (r = 0.45, P < 0.01). The level of miR-126-3p in the intensive glycemic control group was significantly higher than that in the conventional glycemic control group (P < 0.01). Serum exosomal miR-125b-1-3p was not correlated with blood glucose levels (r = 0.03, P > 0.05) and was positively associated with the wound healing rate (r = 0.33, P < 0.05). No significant difference was observed in the level of miR-125b-1-3p between the intensive and conventional glycemic control groups. Regarding the prognosis of diabetic ulcers, the intensive glycemic control group was better than the conventional group (Z = -2.02, P < 0.05). Serum exosome (miR-125b-1-3p and miR-126-3p) levels are correlated with wound healing in diabetic ulcers. Intensive glycemic control increases the serum exosomal miR-126-3p level, which might be one of the mechanisms that promotes wound healing in diabetic ulcers.

ASSOCIATION OF GLYCOSYLLATED HEMOGLOBIN (HbA1C) LEVELS TO THE SEVERITY OF DIABETIC FOOT ULCER IN TYPE 2 DIABETES MELLITUS PATIENTS IN RSUP. H. ADAM MALIK MEDAN

Abstrak&#x0D; Introduction: Diabetic ulcers with neuropathy require amputation or time to fully heal. The worse blood sugar control, it will worsen the condition of complications such as diabetic ulcers, diabetic neuropathy, and other complications. Wound healing in diabetic ulcers is influenced by controlled HbA1c levels.&#x0D; Methods: This study is an observational analytic study with a retrospective design used in this study with secondary data. This study is analytical because it aims to obtain the correlation of HbA1c with the severity of diabetic ulcers in patients with diabetes mellitus at H. Adam Malik Hospital.&#x0D; Results: The average age of the patients was 62 with the majority of respondents being male. The dominance of respondents came with Grade IV as many as 17 people, with uncontrolled HbA1c levels as many as 39 people. Using Spearman Corelation test, the value of r = 0.735, 0.736, and 0.785, respecttively for the corelation between HbA1c, Hb and ESR levels with the severity of diabetic foot ulcers ,with a value (p = 0.0001).&#x0D; Conclusion: We found a strong correlation and a significant relationship between HbA1c, Hb, and ESR levels with the severity of diabetic foot ulcers.

MiR-146a promotes M2 macrophage polarization and accelerates diabetic wound healing by inhibiting the TLR4/NF-κB axis.

We tried to unveil the clinical significance of miR-146a as a biomarker in M2 macrophage polarization in diabetic wound healing. Initially, we found reduced miR-146a in macrophages of diabetic patients. Next, dual-luciferase assay verified that toll-like receptor 4 (TLR4) was a target gene of miR-146 and was negatively regulated by miR-146. Moreover, after ectopic expression and depletion experiments of miR-146 and/or TLR4, lipopolysaccharide-induced inflammatory response of macrophages was detected. The results revealed that overexpression of miR-146a promoted the M2 macrophage polarization by suppressing the TLR4/nuclear factor-kappaB (NF-κB) axis, so as to enhance wound healing in diabetic ulcers. Further, mouse models with diabetic ulcers were established to investigate the effects of miR-146a on diabetic wound healing in vivo, which revealed that miR-146a promoted wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis. In conclusion, we demonstrate that miR-146a can induce M2 macrophage polarization to enhance wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis.

Oxidative Stress and Lipid Peroxidation: Prospective Associations Between Ferroptosis and Delayed Wound Healing in Diabetic Ulcers.

Diabetic ulcers are one of the major complications of diabetes, and patients usually suffer from amputation and death due to delayed ulcer wound healing. Persistent inflammation and oxidative stress at the wound site are the main manifestations of delayed wound healing in diabetic ulcers. In addition, chronic hyperglycemia in patients can lead to circulatory accumulation of lipid peroxidation products and impaired iron metabolism pathways leading to the presence of multiple free irons in plasma. Ferroptosis, a newly discovered form of cell death, is characterized by intracellular iron overload and accumulation of iron-dependent lipid peroxides. These indicate that ferroptosis is one of the potential mechanisms of delayed wound healing in diabetic ulcers and will hopefully be a novel therapeutic target for delayed wound healing in diabetic patients. This review explored the pathogenesis of diabetic ulcer wound healing, reveals that oxidative stress and lipid peroxidation are common pathological mechanisms of ferroptosis and delayed wound healing in diabetic ulcers. Based on strong evidence, it is speculated that ferroptosis and diabetic ulcers are closely related, and have value of in-depth research. We attempted to clarify prospective associations between ferroptosis and diabetic ulcers in terms of GPX4, iron overload, ferroptosis inhibitors, AGEs, and HO-1, to provide new ideas for exploring the clinical treatment of diabetic ulcers.

Comparative study on Photobiomodulation between 630 nm and 810 nm LED in diabetic wound healing both in vitro and in vivo

Photobiomodulation (PBM) promoting wound healing has been demonstrated by many studies. Currently, 630 nm and 810 nm light-emitting diodes (LEDs), as light sources, are frequently used in the treatment of diabetic foot ulcers (DFUs) in clinics. However, the dose–effect relationship of LED-mediated PBM is not fully understood. Furthermore, among the 630[Formula: see text]nm and 810[Formula: see text]nm LEDs, which one gets a better effect on accelerating the wound healing of diabetic ulcers is not clear. The aim of this study is to evaluate and compare the effects of 630[Formula: see text]nm and 810[Formula: see text]nm LED-mediated PBM in wound healing both in vitro and in vivo. Our results showed that both 630[Formula: see text]nm and 810[Formula: see text]nm LED irradiation significantly promoted the proliferation of mouse fibroblast cells (L929) at different light irradiances (1, 5, and 10[Formula: see text]mW/cm[Formula: see text]. The cell proliferation rate increased with the extension of irradiation time (100, 200, and 500[Formula: see text]s), but it decreased when the irradiation time was over 500[Formula: see text]s. Both 630[Formula: see text]nm and 810[Formula: see text]nm LED irradiation (5[Formula: see text]mW/cm[Formula: see text] significantly improved the migration capability of L929 cells. No difference between 630[Formula: see text]nm and 810[Formula: see text]nm LED-mediated PBM in promoting cell proliferation and migration was detected. In vivo results presented that both 630[Formula: see text]nm and 810[Formula: see text]nm LED irradiation promoted the wound healing and the expression of the vascular endothelial growth factor (VEGF) and transforming growth factor (TGF) in the wounded skin of type 2 diabetic mice. Overall, these results suggested that LED-mediated PBM promotes wound healing of diabetic mice through promoting fibroblast cell proliferation, migration, and the expression of growth factors in the wounded skin. LEDs (630[Formula: see text]nm and 810[Formula: see text]nm) have a similar outcome in promoting wound healing of type 2 diabetic mice.

Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes

Extracellular vesicles (EVs) derived from mesenchymal stem cells isolated from both bone marrow (BMSCs) and adipose tissue (ADSCs) show potential therapeutic effects. These vesicles often show a similar beneficial effect on tissue regeneration, but in some contexts, they exert different biological properties. To date, a comparison of their molecular cargo that could explain the different biological effect is not available. Here, we demonstrated that ADSC-EVs, and not BMSC-EVs, promote wound healing on a murine model of diabetic wounds. Besides a general similarity, the bioinformatic analysis of their protein and miRNA cargo highlighted important differences between these two types of EVs. Molecules present exclusively in ADSC-EVs were highly correlated to angiogenesis, whereas those expressed in BMSC-EVs were preferentially involved in cellular proliferation. Finally, in vitro analysis confirmed that both ADSC and BMSC-EVs exploited beneficial effect on cells involved in skin wound healing such as fibroblasts, keratinocytes and endothelial cells, but through different cellular processes. Consistent with the bioinformatic analyses, BMSC-EVs were shown to mainly promote proliferation, whereas ADSC-EVs demonstrated a major effect on angiogenesis. Taken together, these results provide deeper comparative information on the cargo of ADSC-EVs and BMSC-EVs and the impact on regenerative processes essential for diabetic wound healing.

Sprayed copper peroxide nanodots for accelerating wound healing in a multidrug-resistant bacteria infected diabetic ulcer.

Vascular dysfunction and bacterial infection are key factors for the non-healing of diabetic ulcers. Growth factors and antibiotics seem to effectively target both issues. However, the short half-life and high cost of growth factors and the antibiotics resistance of bacteria greatly limit their further widespread applications. Novel strategies or agents with both angiogenic and antibacterial activities are urgently desirable. Copper peroxide (CuO2) nanodots were reported to be decomposed into Cu2+ and H2O2 under mild acid conditions (pH 5.5). Considering that both decomposed products are acknowledged antibacterial agents (Cu2+, H2O2) and angiogenesis activator (Cu2+), we believe that CuO2 nanodots are suitable for diabetic ulcer treatment because the pathological environment of infected chronic wounds is mildly acidic with pH 5.5-5.6. As expected, in vitro experiments showed that CuO2 nanodots possessed excellent bactericidal properties against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and even methicillin-resistant Staphylococcus aureus (MRSA). CuO2 nanodots induced the high expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs), subsequently promoting the cell migration and tube formation for angiogenesis. In particular, CuO2 nanodots exhibited good dispersibility and sprayable behavior in water. In vivo experiments demonstrated that the spayed CuO2 nanodots in the wound area could effectively combat MRSA, reduce inflammation, promote angiogenesis, and consequently accelerate wound healing. Moreover, the sprayed CuO2 nanodots in the wound sites caused negligible system toxicity. This study provides proof-of-principle evidence for applying the sprayed CuO2 nanodots for infected diabetic ulcer treatment.

Measurement of peripheral arterial tonometry in patients with diabetic foot ulcers during courses of hyperbaric oxygen treatment.

Treatment of diabetic foot ulcers is complex and often protracted. Hyperbaric oxygen treatment (HBOT) improves wound healing in diabetic ulcers and serves as an important adjunct to regular diabetic wound care. Endothelial dysfunction plays a central role in diabetes-related vascular complications and may be evaluated by a non-invasive technique called peripheral arterial tonometry which measures a reactive hyperaemia index (RHI). We hypothesized that endothelial function measured by peripheral arterial tonometry is impaired in diabetic foot ulcer patients and that HBOT might improve endothelial function. Endothelial function was prospectively assessed by peripheral arterial tonometry in 22 subjects with diabetic foot ulcers and 17 subjects without diabetes during courses of HBOT. Endothelial function was evaluated before first (baseline) and 30th treatments, and at 90-day follow-up. Serum insulin growth factor-I (IGF-I) concentrations were determined by immunoassay. Results were compared to 23 healthy subjects. No baseline differences were found in endothelial function between subjects with diabetes, HBOT patients without-diabetes and healthy control subjects (RHI; 1.26, 1.61 and 1.81, respectively). No significant changes in RHI were found in patients with (P = 0.17) or without (P = 0.30) diabetes during courses of HBOT. At 90-day follow-up IGF-I was significantly reduced in the subjects with diabetes (P = 0.001) and unchanged in the group without diabetes (P = 0.99). We found no significant differences in RHI between subjects with diabetic foot ulcers and patients without diabetes, nor improvement in endothelial function assessed by peripheral arterial tonometry during courses of HBOT.

ACTIVE SMOKING IS ASSOCIATED WITH DECREASED RATES OF WOUND HEALING AFTER ENDOVASCULAR TREATMENT OF CRITICAL LIMB ISCHEMIA

Previous studies have shown that smoking cessation is associated with improved wound healing in diabetic ulcers, but there are few data for the association between active smoking and wound healing in critical limb ischemia (CLI). CLI patients who underwent endovascular interventions were included.

An excellent nanofibrous matrix based on gum tragacanth-poly (Ɛ-caprolactone)-poly (vinyl alcohol) for application in diabetic wound healing

In this research, the scaffolds from gum tragacanth (GT), poly (Ɛ-caprolactone) (PCL) and poly (vinyl alcohol) (PVA), were fabricated by electrospinning method for use in the healing of diabetic ulcers. At first, three different compositions from PCL-GT-PVA with blend ratios of (2:1:0.5), (2:1:0.8) and (2:1:1.5) were fabricated and the formulation 2:1:0.8 was selected as proper one. Then, the effect of changing GT concentration on the morphology of nanofibers was checked. For this, two different compositions from PCL-GT- PVA (2:1.5:0.8) and (2:2.2:0.8) were electrospun and their morphology was compared with PCL-GT (2:2.2) structure. The results showed that the ratio of (2:2.2:0.8) with more GT in its structure and the mean diameter of 130 ± 19 nm was appropriate one. Since the PCL-GT (2:2.2) formulation was not capable of forming proper fibers, the PCL-GT (2:1) composition was prepared and used for better comparison of PCL-GT-PVA and PCL-GT specimens in subsequent tests. PCL-GT-PVA nanofibers exhibited tensile strength and young modulus about 2.7 and 56 MPa, respectively. Mesenchymal stem cells on the scaffolds demonstrated attachment and proliferation of cells. Histological analyses of substrates containing stem cells into rats with diabetic ulcers exhibited tissue repair and regeneration including re-epithelization and collagen formation after 15 days. We conclude that the fabricated nanofibers with excellent mechanical and biological characteristics are promising scaffolds in wound healing of diabetic ulcers.

A Novel Gold Calreticulin Nanocomposite Based on Chitosan for Wound Healing in a Diabetic Mice Model.

The development of new nanomaterials to promote wound healing is rising, because of their topical administration and easy functionalization with molecules that can improve and accelerate the process of healing. A nanocomposite of gold nanoparticles (AuNPs) functionalized with calreticulin was synthetized and evaluated. The ability of the nanocomposite to promote proliferation and migration was determined in vitro, and in vivo wound healing was evaluated using a mice model of diabetes established with streptozotocin (STZ). In vitro, the nanocomposite not affect the cell viability and the expression of proliferating cell nuclear antigen (PCNA). Moreover, the nanocomposite promotes the clonogenicity of keratinocytes, endothelial cells, and fibroblasts, and accelerates fibroblast migration. In vivo, mice treated with the nanocomposite presented significantly faster wound healing. The histological evaluation showed re-epithelization and the formation of granular tissue, as well as an increase of collagen deposition. Therefore, these results confirm the utility of AuNPs–calreticulin nanocomposites as potential treatment for wound healing of diabetic ulcers.

A Comparative Study of the Effects of Nigella sativa Oil Gel and Aloe Vera Gel on Wound Healing in Diabetic Rats.

Clinicians and wound care nurses in Indonesia usually use Nigella sativa oil (NSO) gel and aloe vera (AV) gel to treat diabetic ulcers. However, there are no studies directly comparing the effects of NSO and AV gels on wound healing, so it is unknown which of these 2 plants is better at promoting wound healing in diabetic ulcers. If the comparative efficacy between these 2 gels was known, it would be important evidence favoring the clinical use of one or the other product in Indonesia. The aim of this study was to investigate and compare the effectiveness of NSO and AV gels on wound healing in a rat model of diabetic ulcers. This experimental study involved 3 groups: NSO gel, AV gel, and controls. Our study showed that from day 5 onward, necrotic tissue and inflammation decreased in the AV gel group compared with the other groups. The wound areas on days 6 (P = .020) and 7 (P = .021) were significantly smaller in the AV gel group than in the NSO gel group. Reepithelialization was also better in the AV gel group than in the other groups. This is the first study to compare the effects of AV and NSO gels on wound healing in diabetic ulcers. Our study indicates that the AV gel is better than the NSO gel. Therefore, it is recommended that clinicians and wound care nurses use AV gel instead of NSO gel for the topical treatment of diabetic ulcers.

A Comparative Study of the Effects of Vibration and Electrical Stimulation Therapies on the Acceleration of Wound Healing in Diabetic Ulcers

Introduction: Diabetic ulcers accompanied by ischemia is difficult to treat. Such ulcers require therapy that can improve the blood flow. Previous studies have revealed that two therapies could improve blood flow and accelerate the healing of diabetic ulcers; vibration and electrical stimulation (ES). However, it is unknown which of these two therapies is best at accelerating wound healing in diabetic ulcers. The purpose of this study was to compare both therapies in relation to accelerating the wound healing of diabetic ulcers.Methods: This study was an experimental study involving diabetic rats. The rats were divided into two groups: vibration and ES. Vibration and ES were applied for 10 minutes per day for 7 days. Wound size, inflammation, intensity of fibroblast infiltration, area of necrosis and degree of re-epithelialisation were compared. The difference in wound size was analysed using an independent t-test, while the histological data were analysed using a Mann-Whitney U-test.Results: On day 5 onwards, there was a thin slough in the ES group which was not present in the vibration group. Day 4 onwards and the wound size was significantly smaller in the vibration group than in the ES group. The intensity of inflammation was significantly less, and the degree of fibroblast infiltration was significantly higher in the vibration group compared with the ES group. Re-epithelialisation was more advanced in the vibration group than the ES group.Conclusion: Our study revealed that wound healing in diabetic ulcers following vibration was better than after ES. We suggest that nurses should use vibration rather than ES in clinical settings.

Diabetic foot ulcers—comparison of performance of ankle-brachial index and transcutaneous partial oxygen pressure in predicting outcome

Diabetic foot ulcer (DFU) is the commonest condition for hospital admission and usually the starting point of most diabetic related lower limb amputations. Considering the significant role played by vascularity in the outcome of ulcer healing, we undertook this study to find out the comparative utility of commonly used vascular assessment methods. This study was a single center prospective non-randomized observational study, conducted for a period of 6 months, in diabetic patients presenting with foot ulcers of Wagner Grade II and III. The aim of our study was to compare the performances of ankle-brachial index (ABI) and transcutaneous partial pressure of oxygen (tcPO2) measurement in predicting wound healing in diabetic ulcers and to define the optimal cut-off value for Indian patients. Five hundred sixty-four patients were included in this study, with the mean age of 58 years. Eighty-seven patients (15%) had peripheral arterial occlusive disease. Four hundred seventy ulcers (83%) healed with the mean healing days of 42.6 days. Age, duration of diabetes, serum creatinine level, and presence of infection were the factors with negative impact in wound healing. In our study, ABI value of 0.6 was found to have 100% sensitivity and 70% specificity, and tcPO2 value of 22.5 was found to have 75% sensitivity and 100% specificity in predicting wound healing. Both ABI and tcPO2 are complementary, but tcPO2 is a better predictor for amputation while ABI is a better predictor for ulcer healing. While assessing the ischemic status of foot ulcer, the cut-off values should be higher in diabetics than non-diabetics.

Effect of Diabetes Condition on Topical Treatment of Binahong Leaf Fraction in Wound Healing Process

Diabetes mellitus (DM) is a metabolic disease which is becoming the first number of health problem in Indonesia, based on the results of the Basic Health Research of Ministry of Health in 2013. One of the diabetes complications affected by high levels of blood glucose is diabetic ulcers wich 85% the number of cases was overed by amputation as the result of improper handling. Herbal treatments could be an alternative treatment of diabetic ulcers, one of them is binahong plant. The results of previous studies have shown the ability of ethanolic extract of binahong leaf in accelerating wound healing in diabetic rats. This study would be a continued study to test five kinds of binahong leaf fractions (FDB) with gradual solvent polarity in accelerating wound healing in diabetic ulcer. Wound healing parameters observed were percentage of wound healing from the wound diameter contraction. The test begins with ethanolic extract of binahong leaf fractionation to produce fractions of hexane (FHDB), chloroform (FKDB), ethyl acetate (FEADB), and ethanol (FEDB). Water fraction (FADB) was obtained from ethanolic leaf extract residues of binahong leaf extraction. Each fraction activity was tested topically twice daily on dorsal of test animals that created wounds using a punch biopsy 5 mm diameters. Grouping of test animals were divided into 13 groups with normal control group (non diabetes), negative control (diabetes + topical application of biocream®), positive control (diabetes + topical application of madecassol), and 10 diabetes groups with topical application of 5 kinds of binahong leaf fractions with each fractions consist of a concentrations of 5% and 10% with biocream® as a vehicle. Diabetic parameters measured include blood glucose levels (KGD) and weight lost percentage (PB%) in day 1 and 10 during a 10-day treatment. The results showed the influence of KGD in the condition of diabetes on wound healing rats diabetic ulcers which topically treated with binahong leaf fractions. FADB 10% has significant differences potention in wound healing process in diabetic rats macroscopically that accelerates wound contraction compared with negative and positive control groups (p&lt;0,05).

Effect of systemic insulin treatment on diabetic wound healing.

This study investigates if different diabetic treatment regimens affect diabetic foot ulcer healing. From January 2013 to December 2014, 107 diabetic foot ulcers in 85 patients were followed until wound healing, amputation or development of a nonhealing ulcer at the last follow-up visit. Demographic data, diabetic treatment regimens, presence of peripheral vascular disease, wound characteristics, and outcome were collected. Nonhealing wound was defined as major or minor amputation or those who did not have complete healing until the last observation. Median age was 60.0 years (range: 31.1-90.1 years) and 58 cases (68.2%) were males. Twenty-four cases reached a complete healing (healing rate: 22.4%). The median follow-up period in subjects with classified as having chronic wounds was 6.0 months (range: 0.7-21.8 months). Insulin treatment was a part of diabetes management in 52 (61.2%) cases. Insulin therapy significantly increased the wound healing rate (30.3% [20/66 ulcers] vs. 9.8% [4/41 ulcers]) (p = 0.013). In multivariate random-effect logistic regression model, adjusting for age, gender, smoking status, type of diabetes, hypertension, chronic kidney disease, peripheral arterial disease, oral hypoglycemic use, wound infection, involved side, presence of Charcot's deformity, gangrene, osteomyelitis on x-ray, and serum hemoglobin A1C levels, insulin treatment was associated with a higher chance of complete healing (beta ± SE: 15.2 ± 6.1, p = 0.013). Systemic insulin treatment can improve wound healing in diabetic ulcers after adjusting for multiple confounding covariates.

Clustering siRNA conjugates for MMP-responsive therapeutics in chronic wounds of diabetic animals.

The MMP-responsive breakdown of siRNA clusters was translated to site-specific gene transfection and enhanced wound healing in diabetic ulcers. MMP-2 siRNA was chemically tethered to the end of multi-armed PEG via MMP-cleavable linkers (4PEG-siRNA) and subsequently clustered into submicron particles complexed with LPEI. 4PEG-siRNA was more tightly complexed with LPEI and the associated cluster showed higher resistance against RNase attack, in comparison to naked siRNA. Because the size of the clusters increased depending on the increase in charge ratio of LPEI to siRNA, cellular uptake of the 4PEG-siRNA/LPEI cluster was significantly attenuated due to the huge size of the cluster. However, upon MMP treatment, the cluster dissociated into smaller particles and was efficiently endocytosed by cells. An in vivo fluorescence resonance energy transfer (FRET) study also revealed that the clusters were effectively dissociated in MMP-rich environments of dorsal wounds in diabetic animals. In addition, diabetic ulcers treated with the clusters showed a faster wound closure rate and the recovered tissue expressed a larger amount of cytokeratin along with a lower expression level of MMP-2 compared to the other groups.