Treatment Of Diabetic Ulcers Research Articles

Hypothesis: Platelet-rich plasma accelerate diabetic wound healing via dynamic modulation of multiple signaling pathways

Diabetic wounds are a prevalent complication in patients with diabetes. Incremental platelet-rich plasma (PRP) administration has recently been used as an adjunct therapy for the treatment of diabetic ulcers. However, the exact signaling pathways involved in PRP-induced healing remain unclear. We speculated that PRP could mediate diabetic wound healing by dynamic modulation of signaling pathways including TGF-β/Smad, Wnt/β-catenin, Notch, NF-κB, MAPK, and PI3K/Akt, at different levels. PRP may have different effects (activation or inhibition) on different or even the same signal pathways depending on the stage of the healing process and concentration of growth factors within the PRP preparation. In the early stages of wound healing, some signaling pathways are initiated to reduce wound inflammation and oxidative stress, and promote angiogenesis and collagen regeneration. In the late stages of wound healing and scar formation, PRP may inhibit some signal pathways to prevent excessive fibroblast proliferation and deposition of extracellular matrix proteins such as collagen, thereby controlling excessive tissue proliferation at the wound site and minimizing scars. The various signaling pathways exhibit complex and context-dependent interactions; crosstalk between these pathways can lead to synergistic or antagonistic effects and regulate various cellular responses. This knowledge could be used to develop targeted therapies to optimize healing and reduce the risk of subsequent complications.

Progressive Platelet Rich Fibrin tissue regeneration matrix: Description of a novel, low cost and effective method for the treatment of chronic diabetic ulcers-Pilot study.

Chronic lower limb ulcers (CLLU) are those injuries that persist for more than six weeks despite adequate care. They are relatively common; it is estimated that 10/1,000 people will develop CLLU in their lifetime. Diabetic ulcer, because of its unique pathophysiology (association between neuropathy, microangiopathy, and immune deficiency), is considered one of the most complex and difficult etiologies of CLLU for treatment. This treatment is complex, costly, and sometimes frustrating, as it is often ineffective, which worsens the quality of life of patients and makes its treatment a challenge. To describe a new method for treating diabetic CLLU and the initial results of using a new autologous tissue regeneration matrix. This is a pilot, prospective, an interventional study that used a novel protocol of autologous tissue regeneration matrix for the treatment of diabetic CLLU. Three male cases with a mean age of 54 years were included. A total of six Giant Pro PRF Membrane (GMPro) were used varying their application between one to three sessions during treatment. A total of 11 liquid phase infiltrations were performed varying their application between three and four sessions. The patients were evaluated weekly and a reduction in the wound area and scar retraction was observed during the period studied. The new tissue regeneration matrix described is an effective and low-cost method for the treatment of chronic diabetic ulcers.

Bioinspired Adaptable Indwelling Microneedles for Treatment of Diabetic Ulcers.

Microneedles provide an effective strategy for transdermal drug delivery. Many endeavors have been devoted to developing smart microneedles that can respond to and interact with pathophysiological environments. Here, novel bioinspired adaptable indwelling microneedles with therapeutic exosome encapsulation are presented for diabetic wound healing by a combined fabrication strategy of template replication and 3Dtransfer printing. Such microneedles are composed of mesenchymal stem cell (MSC)-exosomes-encapsulated adjustable poly(vinyl alcohol) (PVA) hydrogel needle tips and detachable 3M medical tape supporting substrate. As the mechanical strength of the PVA hydrogel is ionically responsive due to Hofmeister effects, the hardness of the resultant microneedle tips can be upregulated by sulfate ions to ensure skin penetration and be softened by nitrate ions after tip-substrate detachment to adapt to the surrounding tissue and release exosomes. Because the MSC-exosomes can effectively activate fibroblasts, vascular endothelial cells, and macrophages, the indwelling microneedles are demonstrated with the function of promoting tissue regeneration and diabetic wound healing in full-thickness cutaneous wounds of diabetic rat models. These features indicate that the bioinspired adaptable indwelling microneedles are with practical values and clinical prospects in tissue and wound regeneration.

Healing Diabetic Ulcers with Pure Honey dressing: Literature Review

Poor peripheral circulation in patients with diabetes mellitus causes wounds to be difficult to heal. Therefore, patients with diabetes mellitus with diabetic ulcers require wound care to reduce the risk of amputation. One alternative material that can be used for wound care is the topical application of pure honey. The purpose of the study was to determine the effect of honey dressing on the healing process of diabetic ulcers through a literature review. The databases used include PubMed, ScienceDirect, Google Scholar, and Garuda. Keywords using (((honey) OR honey dressing) AND wound healing) AND diabetic ulcer) OR diabetic foot ulcer. The library sources used are from 2010-2020. The search results obtained 9,507 articles. Furthermore, articles were selected based on inclusion and exclusion criteria, obtained 11 articles. The assessment of articles uses a checklist on the JBI (Joanna Briggs Institute) assessment list. Eleven articles that met the assessment criteria were then analyzed one by one. The results showed that eleven articles showed the effect of giving honey dressing on the healing process of diabetic ulcers. A total of 3 articles showed wound healing based on changes in score, 2 articles based on changes in grade, 5 articles based on changes in wound characteristics, and 2 articles based on healing time. Of the eleven journals analyzed, honey dressing on diabetic ulcers were most effectively used in wound Grade I and II (Wagner Classification) ulcer patients who received drug therapy with a GDS <200 mg/dL and received daily wound care for 1 month. Healthcare professionals may consider using honey dressings for the treatment of diabetic ulcers. In addition to a more affordable price, honey has good benefits for wound healing. Further research is needed on the type of honey that is more effective as an ingredient in wound care.

COMPREHENSION OF OCCUPATIONAL THERAPIST BACKWARD CHEMOTHERAPY TREATMENT OF DIAMETERS EMBARRASSMENT

Definition of the term JM covers a gaggle of metabolic diseases characterized by elevated blood glucose levels. According to the newest 2016 data from the WHO, 422 million adults live with diameters mellitus. Diameters prevalence is increasing rapidly, because physical inactivity and overweight are risk factors who are increasing too. Embarrassment from diametersmellitus can be treated with physical modalities. The aim of our research was to assess the comprehension of occupational therapists for treatment of embarrassment from diameters mellitus with physical medicine. Material and method: We have designed special questionnaire with 30 inquiries to assess, comprehension for treatment of diabetic food, diabetic ulcer, amputation, and diabetic neuropathy. The data was collected electronically by email. The comprehension was assessed with score: 0-25% poor, 26-50% fair, 51-75%good, 76-100 % excellent. Results: Occupational therapist have had a mean score of 40% of the entire comprehension, rock bottom was backward effect of light therapy on diabetic ulcers and treatment of diabetic neuropathy. Discussion: Treatment of diameters with insulin, is standard in medicine. Physical medicine has important role in prevention of diameters, with promotion of physical activity. Embarrassment of diameters decrease quality of life, with many embarrassment affecting circulation, nerves and bones. Researchers are trying to find new ways of non-pharmacological treatment of embarrassment. Conclusion: Our medical staff have had, fair comprehension backward effect of physical modalities in treatment of embarrassment from JM. Future lectures must contain more attention backward this ill health.

In vitro glycation of a tissue-engineered wound healing model to mimic diabetic ulcers.

Diabetic foot ulcers are a major complication of diabetes that occurs following minor trauma. Diabetes-induced hyperglycemia is a leading factor inducing ulcer formation and manifests notably through the accumulation of advanced glycation end-products (AGEs) such as N-carboxymethyl-lysin. AGEs have a negative impact on angiogenesis, innervation, and reepithelialization causing minor wounds to evolve into chronic ulcers which increases the risks of lower limb amputation. However, the impact of AGEs on wound healing is difficult to model (both in vitro on cells, and in vivo in animals) because it involves a long-term toxic effect. We have developed a tissue-engineered wound healing model made of human keratinocytes, fibroblasts, and endothelial cells cultured in a collagen sponge biomaterial. To mimic the deleterious effects induced by glycation on skin wound healing, the model was treated with 300 µM of glyoxal for 15 days to promote AGEs formation. Glyoxal treatment induced carboxymethyl-lysin accumulation and delayed wound closure in the skin mimicking diabetic ulcers. Moreover, this effect was reversed by the addition of aminoguanidine, an inhibitor of AGEs formation. This in vitro diabetic wound healing model could be a great tool for the screening of new molecules to improve the treatment of diabetic ulcers by preventing glycation.

Bioactive ECM-Loaded SIS Generated by the Optimized Decellularization Process Exhibits Skin Wound Healing Ability in Type I Diabetic Rats.

Patients with diabetes have 15-25% chance for developing diabetic ulcers as a severe complication and formidable challenge for clinicians. Conventional treatment for diabetic ulcers is to surgically remove the necrotic skin, clean the wound, and cover it with skin flaps. However, skin flap often has a limited efficacy, and its acquisition requires a second surgery, which may bring additional risk for the patient. Skin tissue engineering has brought a new solution for diabetic ulcers. Herein, we have developed a bioactive patch through a compound culture and the optimized decellularization strategy. The patch was prepared from porcine small intestinal submucosa (SIS) and modified by an extracellular matrix (ECM) derived from urine-derived stem cells (USCs), which have low immunogenicity while retaining cytokines for angiogenesis and tissue regeneration. The protocol included the optimization of the decellularization time and the establishment of the methods. Furthermore, the in vitro mechanism of wound healing ability of the patch was investigated, and its feasibility for skin wound healing was assessed through an antishrinkage full-thickness skin defect model in type I diabetic rats. As shown, the patch displayed comparable effectiveness to the USCs-loaded SIS. Our findings suggested that this optimized decellularization protocol may provide a strategy for cell-loaded scaffolds that require the removal of cellular material while retaining sufficient bioactive components in the ECM for further applications.

Current and future outlook of loaded components in hydrogel composites for the treatment of chronic diabetic ulcers.

Due to recalcitrant microangiopathy and chronic infection, traditional treatments do not easily produce satisfactory results for chronic diabetic ulcers. In recent years, due to the advantages of high biocompatibility and modifiability, an increasing number of hydrogel materials have been applied to the treatment of chronic wounds in diabetic patients. Research on composite hydrogels has received increasing attention since loading different components can greatly increase the ability of composite hydrogels to treat chronic diabetic wounds. This review summarizes and details a variety of newly loaded components currently used in hydrogel composites for the treatment of chronic diabetic ulcers, such as polymer/polysaccharides/organic chemicals, stem cells/exosomes/progenitor cells, chelating agents/metal ions, plant extracts, proteins (cytokines/peptides/enzymes) and nucleoside products, and medicines/drugs, to help researchers understand the characteristics of these components in the treatment of diabetic chronic wounds. This review also discusses a number of components that have not yet been applied but have the potential to be loaded into hydrogels, all of which play roles in the biomedical field and may become important loading components in the future. This review provides a "loading component shelf" for researchers of composite hydrogels and a theoretical basis for the future construction of "all-in-one" hydrogels.

Outcomes of Keller Gap Arthroplasty for Plantar Hallux Interphalangeal Joint Ulcers in Patients With Diabetes Mellitus.

Hallux ulcers are known for their recurrence and associated risk for future amputations. Traditional nonsurgical external offloading methods have poor compliance rates, and the data is sparse on surgical offloading of hallux ulcers. We performed this study to analyze the outcomes of Keller excision gap arthroplasty of the first metatarsophalangeal joint in patients with a neuropathic plantar hallux interphalangeal joint (IPJ) ulcer in patients with diabetes mellitus. A retrospective study of 105 diabetic patients with a plantar hallux IPJ ulcer who underwent a Keller excision gap arthroplasty between December 2014 and June 2020 was done. A total of 122 great toes had been operated upon for hallux IPJ ulcers. We studied the long-term wound healing rates from patient records and then did a prospective survey of the postreview period. All the hallux IPJ ulcers healed well in the immediate postoperative period. Six patients reported a recurrence of the ulcer at the original site during a mean follow-up period of 30 months. For these 6 patients, the mean time to recurrence of ulcer after operation was 2.5 years. At an average of 30 months, we found the Keller gap arthroplasty for treatment of noninfected and nonischemic diabetic foot hallux IPJ ulcers was associated with an ulcer recurrence rate of 5%. Level IV, cohort study.

Beneficial Effects of a Blended Fibroin/Aloe Gel Extract Film on the Biomolecular Mechanism(s) via the MAPK/ERK Pathway Relating to Diabetic Wound Healing.

In diabetic patients, the process of wound healing is usually delayed or impaired. A diabetic environment could be associated with dermal fibroblast dysfunction, reduced angiogenesis, the release of excessive proinflammatory cytokines, and senescence features. Alternative therapeutic treatments using natural products are highly demanded for their high potential of bioactive activity in skin repair. Two natural extracts were combined to develop fibroin/aloe gel wound dressing. Our previous studies revealed that the prepared film enhances the healing rate of diabetic foot ulcers (DFUs). Moreover, we aimed to explore its biological effects and underlying biomolecular mechanisms on normal dermal, diabetic dermal, and diabetic wound fibroblasts. Cell culture experiments showed that the γ-irradiated blended fibroin/aloe gel extract film promotes skin wound healing by enhancing cell proliferation and migration, vascular epidermal growth factor (VEGF) secretion, and cell senescence prevention. Its action was mainly linked to the activation of the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway known to regulate various cellular activities, including proliferation. Therefore, the findings of this study confirm and support our previous data. The blended fibroin/aloe gel extract film displays a biological behavior with favorable properties for delayed wound healing and can be considered as a promising therapeutic approach in the treatment of diabetic nonhealing ulcers.

Graded stiffness offloading insoles better redistribute heel plantar pressure to protect the diabetic neuropathic foot

BackgroundDiabetic heel ulceration is a common, detrimental, and costly complication of diabetes. This study investigates a novel “graded-stiffness” offloading method, which consists of a heel support with increasing levels of stiffness materials to better redistribute plantar pressure for heel ulcer prevention and treatment. Research questionIs the novel “graded-stiffness” solution better able to redistribute heel pressure and reduce focal stress concentration areas of the heel? MethodsTwenty healthy young men walked with four, 3D-printed, insole configurations. The configurations included the “graded-stiffness” insoles with and without an offloading hole under the heel tissue at risk for ulcerations and two conventional offloading supports of flat insoles with no offloading and simple holed offloading insoles. In-shoe plantar pressure was measured using the Pedar-X system. Peak pressure and pressure dose were measured at three heel regions: offloaded region, perimeter of offloaded region, and periphery region. ResultsThe simple offloading configuration reduced pressure at the offloaded region; however, pressure at the perimeter of the offloading region significantly increased. With respect to ANOVA, the “graded-stiffness” offloading configurations were more effective than existing tested solutions in reducing and redistributing heel peak pressure and pressure dose, considering all heel regions. SignificanceThe “graded-stiffness” offloading solution demonstrated a novel flexible and customized solution that can be manufactured on-demand through a precise selection of the graded-stiffness offloading location and material properties to fit the shape and size of the ulcer. This study is a follow-up in-vivo pilot study, in a healthy population group, to our previous computation modeling work that reported the efficiency of the “graded-stiffness” configuration, and which emphasizes its potential for streamlining and optimizing the prevention and treatment of diabetic heel ulcers.

Sympathetic System in Wound Healing: Multistage Control in Normal and Diabetic Skin.

In this review, we discuss sympathetic regulation in normal and diabetic wound healing. Experimental denervation studies have confirmed that sympathetic nerve endings in skin have an important and complex role in wound healing. Vasoconstrictor neurons secrete norepinephrine (NE) and neuropeptide Y (NPY). Both mediators decrease blood flow and interact with inflammatory cells and keratinocytes. NE acts in an ambiguous way depending on receptor type. Beta2-adrenoceptors could be activated near sympathetic endings; they suppress inflammation and re-epithelialization. Alpha1- and alpha2-adrenoceptors induce inflammation and activate keratinocytes. Sudomotor neurons secrete acetylcholine (ACh) and vasoactive intestinal peptide (VIP). Both induce vasodilatation, angiogenesis, inflammation, keratinocytes proliferation and migration. In healthy skin, all effects are important for successful healing. In treatment of diabetic ulcers, mediator balance could be shifted in different ways. Beta2-adrenoceptors blockade and nicotinic ACh receptors activation are the most promising directions in treatment of diabetic ulcers with neuropathy, but they require further research.

Metformin coordinates with mesenchymal cells to promote VEGF-mediated angiogenesis in diabetic wound healing through Akt/mTOR activation

IntroductionCell therapy with mesenchymal stem cells (MSCs) and biomaterials holds great potential for the treatment of diabetic ulceration; however, the underlying mechanism as well as its compatibility with the first-line anti-diabetic drug, metformin (MTF), has not been well elucidated. MethodsMSCs derived from the umbilical cord were labeled with fluorescent proteins, followed by transplantation in a fibrin scaffold (MSCs/FG) onto the STZ-induced diabetic wound in a C57BL6/J mouse model. MTF was administered by oral gavage at a dose of 250 mg/kg/day. The wound healing rate, epithelization, angiogenesis, and underlying mechanism were evaluated in MSCs/FG- and MTF-treated diabetic wounds. Moreover, the dose-dependent effects of MTF and involvement of the Akt/mTOR pathway were analyzed in keratinocyte and fibroblast cultures. ResultsMSCs/FG significantly promoted angiogenesis in diabetic wound healing without signs of differentiation or integration. The recruitment of fibroblasts and keratinocytes by MSCs/FG promotes migration and vascular endothelial growth factor (VEGF) expression in an Akt/mTOR-dependent manner. MTF, which is generally considered a mTOR inhibitor, displayed dose-dependent effects on MSC-unregulated Akt/mTOR and VEGF expression. Oral administration of MTF at an anti-diabetic dosage synergistically acted with MSCs/FG to promote Akt/mTOR activation, VEGF expression, and subsequent angiogenesis in diabetic wounds; however, it reduced the survival of MSCs. ConclusionsOur study identifies that MTF coordinates with mesenchymal cells to promote Akt/mTOR activation and VEGF-mediated angiogenesis during diabetic wound healing. These findings offer new insights into MSCs engraftment in FG scaffolds for diabetic wound healing and provide support for the promotion of MSCs therapy in patients prescribed with MTF.

Preliminary Application of Contrast-Enhanced Ultrasound in the Treatment of Diabetic Ulcers

To investigate the role of contrast-enhanced ultrasound (CEUS) in the treatment of diabetic ulcers. The clinical data of 27 diabetic patients, who underwent CEUS examination of their ulcers in our hospital between April 2021 and July 2022 were collected. Among them, 26 patients suffered from diabetic foot ulcers, 5 of whom underwent amputation during hospitalization, and one patient suffered from hip ulcer. The 27 patients' mean age was (64.08±12.57) years. Fasting blood glucose levels of the patients were 3.36-34.61 mmol/L, with a mean of (10.62±8.77) mmol/L. Their glycosylated hemoglobin levels were 5.80%-10.70%, with an average of 7.96%±1.50%. Philips EPIQ7 ultrasound system with L9-3 linear probe of 3-9 MHz was used. First, the patients' ulcers were examined with conventional ultrasound to observe for abnormal echo. Then, 2.4 mL SonoVue (Bracco, Italy), a contrast agent, was injected intravenously through the elbow to look for effusion/pus, sinus tract, or dead space in the lesion area, and images were acquired. Among the 27 patients, except for 5 with amputation stumps, 22 patients had wound areas ranging from 0.16 cm 2 to 215 cm 2, all being accompanied by sinus tract formation. Ten patients underwent ultrasound examination during their treatment. The positive rate of the results of conventional ultrasound was 50% (5/10) for identifying effusion/pus and pseudoaneurysm in the deep area of ulcers, while the positive rate of CEUS results was 100% (10/10). In addition to the lesions found by conventional ultrasound, CEUS also found large sinus tracts or dead spaces in the deep surface of ulcers in 5 additional patients. Of the 27 patients, 17 underwent ultrasound examination of the healing status of sinus tracts and dead spaces in the deep areas of ulcers before discharge. No sinus tracts in the deep areas of the ulcers were found by conventional ultrasound. However, relatively small dead spaces or sinus tracts in the deep areas of the ulcers were found in 10 patients by CEUS. Conventional ultrasound and CEUS found that 1 patient had a small amount of fluid in the amputation stump. In the remaining 6 patients, no deep sinus tracts in the ulcers were found by either conventional ultrasound or CUES, and the ulcers healed completely. By examining microvascular perfusion in diabetic wounds with CEUS, we can observe the extent of sinus tracts during treatment and whether the sinus tracts have healed or whether there are still dead spaces before patient discharge, which provides support for clinical decision-making concerning the treatment of diabetic ulcers.

A CO-mediated photothermal therapy to kill drug-resistant bacteria and minimize thermal injury for infected diabetic wound healing.

With an increasing proportion of drug-resistant bacteria, photothermal therapy (PTT) is a promising alternative to antibiotic treatment for infected diabetic skin ulcers. However, the inevitable thermal damage to the tissues restricts its clinical practice. Carbon monoxide (CO), as a bioactive gas molecule, can selectively inhibit bacterial growth and promote tissue regeneration, which may be coordinated with PTT for drug-resistant bacteria killing and tissue protection. Herein, a CO-mediated PTT agent (CO@mPDA) was engineered by loading manganese carbonyl groups into mesoporous polydopamine (mPDA) nanoparticles via coordination interactions between the metal center and a catechol group. Compared to the traditional PTT, the CO-mediated PTT increases the inhibition ratio of the drug-resistant bacteria both in vitro and in diabetic wound beds by selectively inhibiting the co-chaperone of the heat shock protein 90 kDa (Hsp90), and lowers the heat resistance of the bacteria rather than the mammalian tissues. Meanwhile, the tissue-protective proteins, such as Hsp90 and vimentin (Vim), are upregulated via the WNT and PI3K-Akt pathways to reduce thermal injury, especially with a laser with a high-power density. The CO-mediated PTT unified the bacterial killing with tissue protection, which offers a promising concept to improve PTT efficiency and minimize the side-effects of PTT when treating infected skin wounds.

Antibacterial Activity of Mangosteen Leaf and Bark Fraction Against Salmonella spp Causes Diabetic Ulcers

Diabetes mellitus is a degenerative disease due to impaired cell function β-pancreas in insulin production causing hyperglycemics accompanied by microvascular complications such as diabetic ulcers. This condition is aggravated by bacterial contamination, one of which is Salmonella spp. The use of natural ingredients that have the potential for the treatment of diabetic ulcers is the mangosteen plant (Garcinia mangostana L.), so the identification of Salmonella spp in diabetic ulcers and testing the antibacterial activity of ethyl acetate and n-hexan leaves and mangosteen stem skins is carried out. The method started from the stage of bacterial identification using selective media, gram staining, biochemical testing, and antibacterial activity tests by diffusion of discs. Results showed that Salmonella spp was positif in SSA-specific media, biochemical tests, red bacteria, rod-shaped. Antibiotic sensitivity tests obtained by ciprofloxacin had the strongest activity of 30.20±1.37mm. The largest antibacterial activity result at a concentration of 100% obtained the ethyl acetate fraction of mangosteen leaves is 17.30±0.5mm compared to the fraction of n-hexane leaves of 8.81±0.32mm, ethyl acetate fraction and n-hexan mangosteen stem skin of 13.28±0.95mm, 7.42±0.45mm

1690. Assessing the safety of TP-102 bacteriophage treatment in the management of diabetic foot infections

Abstract Background Diabetic Foot Ulcers (DFU) are a major complication in patients with diabetes and affect globally 170 million patients. Approximately 28% of patients with infected DFU require amputation. Diabetic foot infections (DFI) caused by persistent or multidrug resistant organisms are a threat to the outcome of therapy. Infections are mostly polymicrobial, and major pathogens include Staphylococcus aureus and Pseudomonas aeruginosa. A promising new approach using phages may potentially be a novel modality to increase treatment success. TP-102 is an innovative bacteriophage cocktail for treatment of DFI, a diabetes related unmet need. Methods TP-102 comprised of 5 different phages, targeting S. aureus, P. aeruginosa and Acinetobacter baumannii. This study is a Phase I/II clinical trial performed in Israel looking at safety and tolerability. TP-102 bacteriophage cocktail was applied topically at a titer of 109 PFU/mL/cm3 of target ulcer. Two cohorts receive multiple doses of TP-102. In non-infected DFU (cohort 1) for 1 week and for 28 days in DFU with infection grade 2 or 3 (PEDIS classification, cohort 2). Treatment groups were TP-102 with standard of care versus placebo and standard of care. Outcomes include microbiologic data on the 3 target bacteria, ulcer healing characteristics, incidence and severity of TP-102-emergent solicited local and systemic adverse events, and their relationship to the treatment, from the first application of TP-102 until the end of study. Results For the evaluation of safety in patients with non-infected ulcers, eight patients were enrolled to the first cohort. Six were treated with TP-102 and 2 with placebo. TP-102-treated patients had no severe adverse events associated with the treatment. In the second cohort a total of 18 patients are currently being treated with TP-102 or placebo for 28 days, three times a week. Recruitment is ongoing and results of the trial will be presented. Conclusion TP-102 appeared to be safe when applied to patients with uninfected diabetic foot ulcers. The treatment is a potential new non-traditional antimicrobial for topical application. The efficacy of TP-102 in the treatment of infected diabetic ulcers is being assessed in an ongoing randomized clinical trial. Disclosures Ran Nir-Paz, MD, BiomX: Advisor/Consultant|Technophage: Advisor/Consultant Clara Leandro, PhD, Technophage: Employee Raquel Barbosa, PhD, Technophage: Employee Helena Dordio, PhD, Technophage S.A.: Employee Miguel Garcia, n/a, IBV Innovation Bioventures Lda: Board Member|IBV Innovation Bioventures Lda: Ownership Interest|LX Bio Pharmaceuticals SA: Board Member|LX Bio Pharmaceuticals SA: Ownership Interest|TechnoPhage, SA: Board Member|TechnoPhage, SA: Author of several patent applications|TechnoPhage, SA: Ownership Interest.

A comparative study showing effect of local insulin injection on wound vascularization seen in color Doppler imaging in patients with diabetic foot ulcer disease before and after therapy

Background: Diabetic foot ulcer disease is one of the most common complications of diabetes, especially in developing nations like India. Management and successful treatment of diabetic ulcers have been under rigorous research and interventions for the past few decades now. This study is an attempt to analyze the effects of a relatively newer treatment modality for diabetic foot ulcers. Aims and Objectives: The primary objective of this study was to determine results after treating patients of diabetic foot ulcers with local insulin injection therapy and compare with the placebo group after 1 week of treatment. Materials and Methods: In this study, 50 patients with diabetic foot ulcer disease were enrolled, of which 25 patients were randomly selected for the intervention group and the rest were kept in a control group. In the intervention group, patients were treated by injecting insulin preparation at the ulcer site whereas in control group, normal saline was used. Wound assessment was done by measuring the ulcer size and by determining the ankle peak systolic velocity (APSV) using color Doppler technique before and after the treatment in both intervention and control groups. Results: Mean ulcer size before the treatment (7.19 cm2) was higher than post-treatment size (3.48 cm2) and the difference was statistically highly significant (P=0.00) while there was no significant difference in ulcer size post-treatment by insulin or non-insulin (normal saline) group (P=0.274). Mean APSV before the treatment (30.75 cm/s) was lower than post-treatment velocity (43.50 cm/s) and the difference was statistically highly significant (P=0.00) while there was no significant difference in APSV post-treatment by insulin or non-insulin (normal saline) group (P=0.061). Conclusion: It meant that insulin and normal saline were equally effective in reducing ulcer size and improving APSV without being superior to one another.

Effect Of The Combination Of Aloe Vera And Palm Sugar On The Improvement Of Diabetic Ulcers In Patients With Type 2 Diabetes Mellitus

Background: Diabetic ulcer treatment with aloe vera and palm sugar is one of the treatment measures to prevent infection in diabetic ulcers. Aloe vera contains auxin, gibber-relin, anthraquinone, and vitamins A, C, and E as an anti-inflammatory, antipyretic, antioxidant, antiseptic, antimicrobial, as well as antiviral. Aloe vera can diffuse properly and can withstand the loss of body fluids from the surface of the skin so that moisture is maintained, while palm sugar contains vitamin C, Riboflavin, vitamin A, and ascorbic acid as antibiotics and improves the tissue work system which can weaken and kill bacteria that cause infections in diabetic ulcers. Purpose: The purpose of this study was to determine the effect of the combination of aloe vera and palm sugar on the improvement of diabetic ulcers in patients with type 2 diabetes mellitus. Method: One group pretest and posttest design research design in one subject group with a total sample of 8 people, sampling technique using consecutive sampling, the research was carried out in August 2022 at the Wanaraja health center, Garut Regency Results: Based on the results of the study, it is known that the highest activity that occurs in Macaca fascicularis at Sangeh Tourism Object is in the behavior of moves (moving) with a percentage of 17%, and Grooming behavior (Looking for lice) by 15%, then for other activities such as rest (rest) by 14 %, mating 8%, feeding 13%, social 14%, agonistic 13%, for behavior with the lowest percentage of sleep (sleep) of 6%. Conclusion: Conclusion of the study, the combination of aloe vera and palm sugar affects the improvement of diabetic ulcers in patients with type 2 diabetes mellitus

A Pilot Study Comparing a Micronized Adipose Tissue Niche versus Standard Wound Care for Treatment of Neuropathic Diabetic Foot Ulcers.

Numerous studies have demonstrated the various properties of micronized adipose tissue (MAT), including angiogenic, anti-inflammatory, and regenerative activities, which can be helpful in wound healing. This exploratory clinical trial aimed to report the efficacy and safety of MAT niche for treating diabetic foot ulcers. Twenty subjects were randomly divided into MAT niche treatment (n = 10) and control groups (n = 10). All patients were followed up weekly for 16 weeks. We evaluated the efficacy of the MAT niche treatment by assessing the (1) reduction in wound area after 4 weeks and (2) percentage of patients who achieved complete wound closure after 16 weeks. All possible adverse events were recorded. The wound area was reduced by 4.3 ± 1.0 cm2 in the treatment group and by 2.0 ± 1.1 cm2 in the control group (p = 0.043). Complete wound healing was achieved after 16 weeks in eight out of 10 patients (80%) in the treatment group and three out of six (50%) in the control group (p = 0.299). No serious adverse events related to MAT niche treatment were observed. Although the present study’s findings do not support the use of this therapy to treat foot ulcers of patients with diabetes owing to the small number of patients included and the absence of statistical significance, the results of this pilot preliminary study are promising in that MAT niche autografts may offer the possibility of a simple and effective treatment for diabetic ulcers. Further follow-up studies with a larger number of patients are required to validate our findings.