Healing Of Foot Ulcers Research Articles

Astragalus Polysaccharides/PVA Nanofiber Membranes Containing Astragaloside IV-Loaded Liposomes and Their Potential Use for Wound Healing.

Delayed wound healing is a common and serious complication in diabetic patients, especially the slow healing of foot ulcers, which seriously affects the quality of life of patients and is also the most important risk factor for lower limb amputation. The multifunctional novel dressing prepared by loading the polymer nanofibers with anti-inflammatory and prohealing plant extracts can promote the wound repair of these ulcers by electrospinning technology. Liposomes are nanoparticles prepared from phospholipids and have been widely used as drug delivery systems. Liposomes can be combined with electrospun nanofibrous webs to facilitate local and sustained delivery of loaded bioactive substances. In this study, liposomes were prepared with astragaloside IV (AS) by employing a modified ethanol injection method and conducting the physical and chemical characterization (e.g., the particle size, polydispersity index, zeta potential, and entrapment efficiency). Astragalus polysaccharides were extracted from Astragalus membranaceus. Subsequently, we prepared the electrospun polyvinyl alcohol (PVA)/astragalus polysaccharide (APS)/astragaloside IV (AS) nanofibers. The morphology of the produced ASL/APS/PVA, APS/PVA, and PVA nanofibers were analyzed by scanning electron microscopy (SEM), and it turns out that the addition of astragalus extract made the fiber diameter smaller and the fibers arranged neatly with no dripping. An induced diabetic rat model was built, and a diabetic ulcer model was built by total cortical resection to assess the prorepair ability of the prepared nanofibers. According to in vivo animal experiments, the nanofibrous membrane loaded with APS and ASL was reported to inhibit the occurrence of wound inflammation, enhance the deposition of collagen fibers (P < 0.05) and the repair of regenerated epithelium (P < 0.05), and effectively strengthen the wound healing of diabetic rats (P < 0.05). In brief, PVA-loaded APS/ASL nanofibrous membranes refer to a prominent wound healing dressing material, which can effectively facilitate the healing of diabetic wounds, and they are demonstrated to be highly promising for application in diabetic wound dressings and tissue engineering.

A Feasibility and Safety Study of a Novel Human Decellularized Dermal Matrix to Accelerate Healing of Neuropathic Diabetic Foot Ulcers in People With Type 1 and Type 2 Diabetes

ObjectivesThe purpose of this study was to determine the feasibility and safety of a novel decellularized dermal matrix (DDM) for the treatment of chronic diabetic foot ulcers (DFUs). MethodsAn interventional, single-arm, prospective study of DDM for DFU treatment was conducted in 2 Canadian centres from July 1, 2016, to May 30, 2017. Individuals ≥18 years of age with an active DFU of ≥2 weeks and ulcer area ≥1 cm2 before debridement and who consented to participate were enrolled in this clinical trial. ResultsA total of 11 patients were enrolled, with 9 patients (82%) having achieved 100% closure between 2 and 8 weeks. The mean and median times to wound closure for these patients were 3.3 and 2.5 weeks, respectively. The mean and median reductions in wound area at 4 weeks posttreatment were 87% and 100%, respectively. The proportion of patients having achieved complete healing at 12 weeks was 82%. All patients received only 1 DDM application to achieve these results. There were no adverse events related to use of the product. No cases of recurrence during a 1-year follow-up after completion of the study were reported for patients who achieved wound closure. ConclusionsThese findings provide evidence that this DDM may be safe and effective for the treatment of chronic, hard-to-heal neuropathic DFUs. Specifically, DDM demonstrated the potential to accelerate healing of DFUs when compared with reported times of 8 to 12 weeks required to achieve closure using the current standard of care.

IDF21-0620 Results of split thickness skin grafts in revascularized diabetic foot ulcers patients

Background: Split thickness skin grafts (STSG) have been shown to improve healing of diabetic foot ulcers (DFU) in non-ischemic patients. There were no previous studies to assess the results of STSG in ischemic revascularized legs. Aim: To assess the results of STSG in patients presenting with DFU and critical limb threatening ischemia (CLTI), who underwent revascularization, in comparison with non-ischemic patients. Method: Retrospective case control study. The data of all consecutive patients who had STSG for DFU at our center between 1st of January 2020 and 31 of December 2020 were reviewed. They were divided into two groups: group A included patients with CTLI who underwent revascularization prior to STSG, and group B included non-ischemic patients who had STSG. DFU were treated along standard lines regarding debridement, off-loading of plantar ulcers, and treatment of infection. DFU in CLTI were treated by revascularization, using endovascular approach mainly. Optimization of the general condition was performed prior to STSG. Negative pressure wound therapy was applied until the wound was covered with healthy granulations, then STSG was performed. All patients were followed for a minimum of 6 months. End points were rate of healing, duration of complete wound healing, major amputation and death. Results: There were 61 patients: Group A: 37 & Group B 24. 78% were male and all were diabetics. No statistical differences were found between both groups regarding the demographic factors and risk factors, and the local wound condition regarding size, location, and wound class according to WIFI classification. Complete wound healing was achieved in 80% in group A versus 92.3% for group B within 6 months (NS). The mean time to complete healing was 31.5 (SD 44.7) days in Group A and 22.2 (SD 21.5) days in group B (NS). One patient had major amputation due to infection and 2 patients died due to unrelated causes, all were in group A. Discussion: STSG was not previous reported following revascularization in patients suffering CLTI and DFU. Although this study showed longer time to achieve complete wound healing in revascularized patients as compared to non-ischemic DFU, the healing rate of the revascularized group (80%) and the mean healing time (31.5 days) were still improved as compared to our own historical data of non-ischemic patients with DFU who did not receive STSG.

Optimization of photo-biomodulation therapy for wound healing of diabetic foot ulcers in vitro and in vivo.

Unclear optical parameters make photo-biomodulation (PBM) difficult to implement in diabetic foot ulcer (DFU) clinically. Here, 12 wavelengths (400-900 nm) were used to conduct PBM to heal DFU wounds in vitro and in vivo. PBM at 10 mW/cm2 and 0.5-4 J/cm2 with all 12 wavelengths promoted proliferation of diabetic wound cells. In a mimic DFU (mDFU) rat model, PBM (425, 630, 730, and 850 nm, and a combination light strategy) promoted mDFU healing. The positive cell proliferation, re-epithelialization, angiogenesis, collagen synthesis, and inflammation were possible mechanisms. The combination strategy had the best effect, which can be applied clinically.

Topical Administration of Lactiplantibacillus plantarum Accelerates the Healing of Chronic Diabetic Foot Ulcers through Modifications of Infection, Angiogenesis, Macrophage Phenotype and Neutrophil Response.

This work aimed to evaluate the adjuvant treatment to surgical debridement using topical applications of Lactiplantibacillus plantarum ATCC 10241 cultures in complicated diabetic foot ulcers as compared to diabetic foot ulcers receiving surgical wound debridement. A randomised controlled trial was performed involving 22 outpatients with complicated diabetic foot ulcers that either received surgical debridement (SuDe, n = 12) or surgical debridement plus topical applications of L. plantarum cultures (SuDe + Lp, n = 10) every week during a 12 week treatment period. Compared to patients receiving SuDe, patients treated with SuDe + Lp exhibited significantly increased fibroplasia and angiogenesis, as determined by Masson’s trichrome staining and the study of CD34 cells, α-smooth muscle actin to semi-quantify vascular area, number of vessels and endothelial cells. In addition, a promotion of the polarisation of macrophages from M1 (CD68) to M2 (CD163) phenotype was observed in SuDe + Lp patients with remarkable differences in the tissue localisation. Bacterial counts were significantly diminished in the SuDe + Lp group compared to the SuDe group. Ex vivo assays, using polymorphonuclears isolated from peripheral blood of patients with diabetes and healthy individuals and challenged with Staphylococcus aureus demonstrated that the addition of L. plantarum supernatants significantly improved the phagocytosis of these cells. L. plantarum-secreted components increased the neutrophils bactericidal activity and regulated the netosis induced by S. aureus. At day 49, the average wound area reduction with SuDe + Lp was 73.5% compared with 45.8% for SuDe (p < 0.05). More patients progressed to closure with SuDe + Lp compared with SuDe treatment, indicating the ability of L. plantarum to accelerate the healing. At day 60, 60% of patients treated with SuDe + Lp achieved 100% of wound area reduction compared with 40% for SuDe. We propose that SuDe + Lp could be an effective adjuvant to surgical debridement when SuDe is not satisfactory for patients with complicated diabetic foot ulcers. The treatment is cheap and easy to apply and the product is easy to obtain.

The Effect of Topical Cow's Milk on the Healing of Diabetic Foot Ulcers: A Randomized Controlled Pilot Clinical Trial.

Diabetic foot ulcer (DFU) is a very serious side effect among the diabetic patients with substantial clinical and economic consequences. The aim of this study was to investigate the efficacy of cows' milk topical ointment, as an available and cost-effective natural product, on accelerating the healing of DFU. In this randomized controlled clinical trial, patients with grade 1 or 2 DFU were randomly divided into two groups of intervention (n = 50) and control (n = 49). For patients of intervention group, cows' milk 20% topical ointment was applied on the ulcer once daily for two weeks, while a type of novel dressing was used for control group with the same frequency and duration. Both groups received usual standard wound care measures. The percentage of change in the ulcer size and the number of cases with complete wound healing (>90% reduction in the ulcer size) were recorded in the both groups. The ulcer size significantly reduced in both groups on the seventh and 14th days of intervention; however, the percentage of reduction was significantly higher in the intervention (milk) group compared to control at both time points (44.64 ± 15.98 vs. 24.95 ± 12.78, P < .001; 67.67 ± 22.15 vs. 42.87 ± 19.74, P < .001). Furthermore, although more patients in the intervention group (n = 4, 8%) showed complete healing of the ulcer compared to control (n = 0), the difference was not statistically significant (P = .117). Cow's milk 20% topical ointment improves and accelerates the healing of diabetic foot ulcers. However, more clinical studies are required to confirm these effects.

Healing of diabetic foot ulcers is independently associated with the use of angiotensin receptor blockers but not with those of diuretics and angiotensin conversion enzyme inhibitors

Aim. Dysregulation of the renin angiotensin system (RAS) has been proven in diabetic animal models, and studies in humans show that diuretic use is associated with lower limb amputation in diabetes. While patients with diabetes are often treated with diuretics and RAS blockers, the association between wound healing and these treatments is still unknown. We aimed to determine whether the use of diuretics and RAS blockers could influence healing of diabetic foot ulcers (DFU).Methods. Two hundred seventy-six patients referred to a specialized diabetes foot care unit for a new foot ulcer were included in this retrospective observational study.Results. Healing rate was significantly higher in patients not treated with diuretics than in those receiving diuretics (75.9 vs. 62.9%, P = 0.026) and in patients treated with angiotensin receptor blockers (ARB) than in those not treated with ARB (79.5 vs 64.4%, P = 0.012). The difference was not significant for angiotensin conversion enzyme inhibitor use. ARB use was independently and positively associated with wound healing in a multivariate adjusted model including several factors affecting wound healing (odds ratio (OR) 2.79 [1.13, 6.86] P = 0.025). Diuretic use was negatively associated with wound healing in univariate analysis (OR 0.54 [0.32, 0.91] P = 0.02) but not in multivariate adjusted analysis (OR 0.53 [0.26, 1.10] P = 0.088).Conclusions. This novel study found that ARB use is independently and positively associated with wound healing in 276 patients with DFU. On the contrary, diuretics were associated with healing rate only at univariate analysis. Further prospective studies are needed to confirm our findings.

Insight on Hyperbaric Oxygen Therapy as an Adjunctive Treatmentin Diabetic Foot Ulcer: A Review

Diabetic foot ulcers (DFU) are a source of major concern for both patients and health care systems. DFU is the most expensive and devastating complication of diabetes mellitus, which affect 15% of diabetic patients during their lifetime. That can lead to infection, gangrene, amputation, and even death if necessary care is not provided. On the other hand, once DFU has developed, there is an increased risk of ulcer progression that may ultimately lead to amputation. Overall, the rate of lower limb amputation in patients with diabetes mellitus is 15 times higher than patients without diabetes. Hyperbaric oxygen therapy (HBOT) can be defined as a mode of medical treatment in which the patient is entirely enclosed in a pressure chamber and breathes 100% oxygen at a pressure greater than 1 atmosphere absolute (ATA). HBOT can be used as an adjunct to standard wound care in the treatment of diabetic patients with foot ulcers. HBOT has been demonstrated to have an antimicrobial effect and to increase oxygenation of hypoxic wound tissues. This enhances neutrophil killing ability, stimulates angiogenesis, and enhances fibroblast activity, collagen synthesis and alter vascular activity. Thus, theoretically, HBOT could improve the healing of ischemic foot ulcers in patients with diabetes. This review focuses on providing an up-to-date summary of the currently available evidence-based data on HBOT in DFU, as well as elaborating its use in the management of diabetic injuries both ischemic and non-ischemic ulcers.

Role of ultrathin skin graft in early healing of diabetic foot ulcers: a randomized controlled trial in comparison with conventional methods.

Diabetic foot ulcers (DFUs) are a global burden on health care systems. Despite the availability of various treatment modalities, many DFUs do not heal. Nonhealing wounds can lead to various complications, which add to significant morbidity in terms of the degree of moisture retained in the dressing, pain, foul order, and restriction of daily activities. A different treatment modality that can promote the wound healing process earlier (and is cost-effective, easy to use, and readily available) may be necessary to consider. The purpose of the current study was to demonstrate the efficacy of ultrathin skin grafting (UTSG) in the early healing of DFUs in terms of cost-effectiveness, reduced total number of hospital visits, and final wound outcome (ie, limb salvage rate). A randomized controlled trial was conducted in which 52 patients were treated with either UTSG (test group) or conventional dressing (control group). Both groups were compared by time to healing, number of hospital visits, cost, and final outcome of the wound. By the end of the 12-week study period, 84.61% of wounds managed with UTSG healed completely, whereas only 53.84% of wounds managed with conventional methods achieved complete healing. The test group achieved a more than 50% wound size reduction within 6 weeks after grafting. There were fewer hospital visits for the test group, indicating this grafting technique was more cost-effective than the control group. As demonstrated in this study, UTSG appears to be beneficial in achieving faster healing of DFUs and improving the final outcome of the wound.

Clinically relevant experimental rodent models of diabetic foot ulcer.

Chronic wounds are a substantial clinical problem in diabetes and nearly 6% of diabetics suffer from foot disease including ulceration, infection, and tissue necrosis. Wound healing in diabetes is impaired and delayed and is augmented by diabetic complications. Wound healing involves complex cellular, molecular, and biochemical processes and animal models are the most suitable prototype to investigate and understand the underlying pathological changes in the process of wound healing. Animal models are also useful in evaluating the safety and efficacy of newer therapeutic agents and improving the clinical approaches for human patients with chronic ulcers. The wound healing strategies get more complicated in the presence of diabetes and its associated complication. Despite the advancement in methods of wound healing, the healing of the chronic diabetic foot ulcer (DFU) remains an important clinical problem resulting in costly and prolonged treatment and poses a risk for major amputation. Saying that it is important to elucidate the newer therapeutic targets and strategies via an in-depth understanding of the complicated cascade of the chronic DFU. A major challenge in translating lab findings to clinics is the lack of an optimal preclinical model capable of properly recapitulating human wounds. Both small and large animal models of wound healing involving rodents, rabbits, and pigs have been discussed. Mouse and rats as small animal models and pig as large animal models have been discussed in association with the diabetic wound but there are advantages and limitations for each model. In this review, we critically reviewed the pros and cons of experimental models of diabetic wound healing with a focus on type II diabetes rodent models.

The Effect of Plantago major Hydroalcoholic Extract on the Healing of Diabetic Foot and Pressure Ulcers: A Randomized Open-Label Controlled Clinical Trial.

Aims: Diabetic foot ulcer (DFU) and pressure ulcer (PU) both are common types of ulcers worldwide. The wound healing effect of Plantago major leaves has been shown in a few animal studies. This study aimed to evaluate the clinical efficacy of P. major hydroalcoholic extract on DFU and PU healing. Methods: In this clinical trial, patients with DFU or PU who met the inclusion criteria were randomly assigned to drug (P. major) or control groups. For patients in the drug group, Plantago extract 10% topical gel was applied on the wound once daily concurrent with dressing and routine wound care for two weeks, while for the control group, an appropriate novel dressing was used along with routine wound care for the same duration. The percentage of wound size reduction at the end of the seventh and 14th days of intervention was recorded and compared between the groups. Results: Fifty and 44 patients in drug and control groups, respectively, completed the interventions. Plantago extract gel significantly resulted in more reduction in the wound size compared to control at the end of the first (64.90 ± 29.75% vs. 33.11 ± 26.55%; P < 0.001) and second week (86.85 ± 24.34% vs. 52.87 ± 32.41%; P < 0.001). Furthermore, the number of patients with complete wound healing in the drug group (n = 32, 64%) was significantly more than the control group (n = 9, 20.45%; OR: 3.129, 95% CI: 1.685-5.809, P < 0.001). Conclusion: The use of 10% topical gel of P. major leaf extract results in the acceleration of DFU and PU healing. Key points: Application of P. major topical gel results in the acceleration of diabetic foot ulcer and pressure ulcer healing. - P. major extract helps reducing the wound's erythema.- P. major leaf extract assists decreasing the wound size.- The number of patients completing wound healing process is higher among whom undergoing P. major dressing.

3D bioprinted scaffolds for diabetic wound-healing applications

The treatment strategy required for the effective healing of diabetic foot ulcer (DFU) is a complex process that is requiring several combined therapeutic approaches. As a result, there is a significant clinical and economic burden associated in treating DFU. Furthermore, these treatments are often unsuccessful, commonly resulting in lower-limb amputation. The use of drug-loaded scaffolds to treat DFU has previously been investigated using electrospinning and fused deposition modelling (FDM) 3D printing techniques; however, the rapidly evolving field of bioprinting is creating new opportunities for innovation within this research area. In this study, 3D-bioprinted scaffolds with different designs have been fabricated for the delivery of an antibiotic (levoflocixin) to DFU. The scaffolds were fully characterised by a variety of techniques (e.g. SEM, DSC/TGA, FTIR, and mechanical characterisation), demonstrating excellent mechanical properties and providing sustained drug release for 4 weeks. This proof of concept study demonstrates the innovative potential of bioprinting technologies in fabrication of antibiotic scaffolds for the treatment of DFU.Graphical abstract

Maggot treatment promotes healing of diabetic foot ulcer wounds possibly by upregulating Treg levels

PurposeThrough the study of regulatory T cells (Tregs), we found a possible way to promote the healing of diabetic foot ulcers (DFUs) with maggot treatment and investigated the associated mechanism. MethodsImmunohistochemistry was used to examinetissues from DFU patients treated with or without maggot debridement therapy (MDT). The expression of the signature Treg molecule Foxp3, interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), and interferon regulatory factor 4 (IRF-4) in patients with DFU treated with or without MDT was tested by real-time PCR (RT-PCR). CD4+ T cells from mouse spleen cells were cocultured in vitro with maggot excretions/secretions (ES), and Foxp3, IL-10, TGF-β, and IRF-4 levels were measured by RT-PCR. ResultsFoxp3 expression was obviously increased in DFU patients treated using MDT but less pronounced in those treated without MDT (P < 0.05). Foxp3, IL-10, TGF-β, and IRF-4 gene expression levels were higher in DFU patients treated with MDT than in those treated without MDT. Moreover, in vitro coculture of mouse spleen cells with ESs produced results consistent with the in vivo results (P < 0.001). ConclusionMDT/ESs can obviously upregulate the Treg level and may affect DFU healing in different ways, suggesting a new direction for the future treatment of DFU.

Improving Diabetic Foot Ulcer Healing with Adjuvant Bitter Melon Leaf Extract (Momordica charantia L.)

BACKGROUND: Diabetes mellitus is a serious disease that affects more than 340 million people and causes approximately 20% of diabetic ulcer cases worldwide. Wound healing is a complex and dynamic process in restoring cellular structures and tissue layers. It consists of four continuous overlapping phases that are precisely programmed AIM: This study aims to examine the adjuvant administration of bitter melon leaf extract to increase the healing of diabetic foot ulcers (DFU). METHODS: This study used a randomized, double-blind, and placebo-controlled trial. A total of 30 DFU patients with a perfusion, extent, depth, infection, and sensation (PEDIS) score of 1–8 who met the criteria were divided into two groups, namely, the treatment group with adjuvant administration of bitter melon leaf extract at a dose of 6 g/day as many as 15 patients and the control group 15 patients with placebo. This intervention was carried out for 4 weeks. DFU cure was measured by PEDIS scores at baseline, weeks 2, 3, and the end of week 4. Data were analyzed using paired t-test and independent t-test. RESULTS: After 4 weeks of treatment, the PEDIS score in the treatment group decreased at week 2 (0.9 ± 1.8), but not significant (p = 0.19), decreased at week 3 (1.9 ± 1.9) and significant (p = 0.01), decreased in week IV (2.3 ± 2.1) and significantly (p = 0.001). The control group experienced a decrease in week 2 (0.3 ± 2.3), but not significant (p = 0.71), decreased in week 3 (1.2 ± 2.5), but not significant (p = 0.18), decreased in week 4 (1.9 ± 2.7) and significantly (p = 0.03), and there was an effect of adjuvant administration of bitter melon leaf extract on the cure of DFU (p = 0.004). CONCLUSION: Adjuvant administration of bitter melon leaf extract has been shown to increase the healing of DFU.

Australian guideline on wound healing interventions to enhance healing of foot ulcers: part of the 2021 Australian evidence-based guidelines for diabetes-related foot disease

BackgroundDiabetes-related foot ulceration (DFU) has a substantial burden on both individuals and healthcare systems both globally and in Australia. There is a pressing need for updated guidelines on wound healing interventions to improve outcomes for people living with DFU. A national expert panel was convened to develop new Australian evidence-based guidelines on wound healing interventions for people with DFU by adapting suitable international guidelines to the Australian context.MethodsThe panel followed National Health and Medical Research Council (NHMRC) procedures to adapt suitable international guidelines by the International Working Group of the Diabetic Foot (IWGDF) to the Australian context. The panel systematically screened, assessed and judged all IWGDF wound healing recommendations using ADAPTE and GRADE frameworks for adapting guidelines to decide which recommendations should be adopted, adapted or excluded in the Australian context. Each recommendation had their wording, quality of evidence, and strength of recommendation re-evaluated, plus rationale, justifications and implementation considerations provided for the Australian context. This guideline underwent public consultation, further revision and approval by ten national peak bodies.ResultsThirteen IWGDF wound healing recommendations were evaluated in this process. After screening, nine recommendations were adopted and four were adapted after full assessment. Two recommendations had their strength of recommendations downgraded, one intervention was not currently approved for use in Australia, one intervention specified the need to obtain informed consent to be acceptable in Australia, and another was reworded to clarify best standard of care. Overall, five wound healing interventions have been recommended as having the evidence-based potential to improve wound healing in specific types of DFU when used in conjunction with other best standards of DFU care, including sucrose-octasulfate impregnated dressing, systemic hyperbaric oxygen therapy, negative pressure wound therapy, placental-derived products, and the autologous combined leucocyte, platelet and fibrin dressing. The six new guidelines and the full protocol can be found at: https://diabetesfeetaustralia.org/new-guidelines/ConclusionsThe IWGDF guideline for wound healing interventions has been adapted to suit the Australian context, and in particular for geographically remote and Aboriginal and Torres Strait Islander people. This new national wound healing guideline, endorsed by ten national peak bodies, also highlights important considerations for implementation, monitoring, and future research priorities in Australia.

Downregulation of hsa-miR-203 in peripheral blood and wound margin tissue by negative pressure wound therapy contributes to wound healing of diabetic foot ulcers.

Negative pressure wound therapy (NPWT) has been widely used in the treatment of chronic wounds, including diabetic foot ulcers (DFU) as the severe manifestation of diabetic foot. Hsa-miR-203 is proven to be correlated with the severity of DFU. To investigate whether NPWT influences hsa-miR-203 levels in persons with DFU, we detected hsa-miR-203 levels in peripheral plasma and wound margin tissue from the following patients: type 2 diabetic (T2D) patients with DFU (DFU group), T2D patients without DFU (NDFU group), patients with chronic skin ulcer and normal glucose tolerance (SUC group), and healthy volunteers with normal glucose tolerance (NC group). All patients in SUC group received NPWT. As contrast, some of patients in DFU group received NPWT (NPWT group) while others chose routine dressing therapy (non-NPWT group). In vitro experiments were also performed to determine influences of negative pressure on cell proliferation and migration of HaCaT cells (human keratinocytes). Results showed that before NPWT, levels of hsa-miR-203 in peripheral plasma (P-miR-203) and wound margin tissue (T-miR-203) of DFU group were obviously increased compared to SUC group while expression of P-miR-203 decreased in NDFU group compared with NC group. After NPWT, levels of P-miR-203 and T-miR-203 in DFU and SUC group were significantly lower than before. Changes of P-miR-203 and T-miR-203 after NPWT were positively correlated with 4-week ulcer healing rate in NPWT and SUC group. In vitro, negative pressure lowered the expression of hsa-miR-203, enhancing cell proliferation and migration in HaCaT cells via up-regulation of p63 protein. Meanwhile, the effects of negative pressure on cells were remarkable reduced by high-glucose intervention. Our study suggests that NPWT promotes DFU healing by reducing the expression of hsa-miR-203 in peripheral blood and wound tissue. The changes of hsa-miR-203 in peripheral blood and wound tissue may be related to the therapeutic effect of NPWT.

Study the Effectiveness of Vacuum Assisted Closure Therapy in the Healing of Chronic Diabetic Foot Ulcer

Aim: To determine the effectiveness of vacuum assisted closure(vac) therapy in the healing of chronic diabetic foot ulcer.&#x0D; Methodology: A prospective study was conducted among the patients who were admitted and treated for diabetic foot ulcer in Saveetha Medical College And Hospital over a period of 6 months from January 2021 to June 2021. There were about 15 patients admitted and treated for the same.&#x0D; Results: An aggregate of 15 patients were remembered for the review. Among them 62% (n=9) were male and 38% (n=6). Age range was from 30 to 70 years with a mean age of 50 ± 9.75 years. The recurrence of VAC dressing change was following 24-48 hours for 75% (n=11) wounds, like clockwork for 15% (n=4) wounds. Larger part of patients (92.5%, n=13) don't need extra debridement over the span of VAC treatment. Normal decrease in injury region noticed was 11.4 ± 4.55 cm2 (territory, 3.4 to 38.6cm2) and the normal season of recuperating noticed was 21.75±10.55 days (range, 14 to 4 days).&#x0D; Conclusion: VAC treatment is exceptionally powerful and helpful in the treatment of diabetic foot disease and ulcers and plays an authoritative part upgrading granulation tissue arrangement, wound size decrease, recuperating of twisted in lesser time.

Autologous Platelet Rich Plasma Promotes the Healing of Non-Ischemic Diabetic Foot Ulcers. A Randomized Controlled Trial

DFU (diabetic foot ulcer) represents a major global health and socioeconomic problem and a leading cause of lower limb amputation. Although many therapies have been tested, none has been proposed as a dominant wound healing treatment. We performed a prospective randomized controlled study in order to assess the role of autologous platelet rich plasma (PRP) for the promotion of non-ischemic DFU healing. After full vascular assessment, a total of 80 patients were randomized in 1:1 ratio to receive either PRP injection in the healing edge and the floor of the targeted DFU (Group A), or have usual standard care with moist dressing with or without collagenase ointment (Group B). We calculated the total surface area (TSA) for the ulcer in both groups (cm2) before, after treatment and every week up to 12 weeks of follow-up. A total of 4 patients (10%) experienced major amputation in group B, while no major amputation was performed in patients of Group A (P< 0.001). A ≥ 50% reduction in TSA occurred earlier in Group A (at 2.5 weeks), compared to Group B (4.5 weeks); P < 0.001. Complete wound healing rate was 95% (n=38) and it was achieved earlier (6th week) for patients of group A, contrary to 77.8% (n=28) of patients (9th week) for Group B (P < 0.001). Superficial wound infection was noted in 10% (n=4) of the cases in the PRP arm, while in group B, 45% (n=18) of cases had a variable degree of infection ranging from superficial to deep wound infection and cellulites (P < 0.001). PRP treatment was cost-effective, with 247.50$ vs. 437.50$ for the total cost of treatment for patients of Group B. PRP is a cost-beneficial novel modality of treatment that can accelerate wound healing and decrease the rate of local infection in DFU, compared to other conventional treatment modalities.

MF-094, a potent and selective USP30 inhibitor, accelerates diabetic wound healing by inhibiting the NLRP3 inflammasome

Diabetes is a prevalent disease worldwide that can result in several complications, including renal failure, blindness, and amputation. Diabetic foot ulcers, which have the characteristics of chronic wounds, are a devastating component of diabetes progression that can lead to lower extremity amputation. In this study, we set out to investigate the mechanisms involved in wound healing of diabetic foot ulcers. The expression of USP30 in skin tissues of patients with diabetic foot ulcers and HSF2 human skin fibroblasts treated with advanced glycation end (AGE) products was detected by qRT-PCR, and CCK-8, cell scratch and ELISA assay were used to detect cell viability, migration and levels of Col I, Col III, MMP-2, MMP-9, IL-1β and IL-18. The interaction between USP30 and NLRP3 was verified by co-immunoprecipitation and ubiquitination assays. The expression of USP30, NLRP3 and caspase-1 p20 was detected by Western blot. USP30 inhibitor MF-094 was used to treat diabetic rat model established by streptozotocin (STZ). We found that USP30, a deubiquitinase, was upregulated in skin tissues of patients with diabetic foot ulcers compared with normal skin tissues. In vitro, we found that treatment of HSF2 human skin fibroblasts with advanced glycation end (AGE) products, known to contribute to diabetic complications, resulted in suppressed viability and migration of HSF2 cells, as well as increased levels of USP30 mRNA and protein. Functionally, downregulation of USP30 via shRNA-mediated knockdown or treatment with the USP30 inhibitor MF-094, restored viability and migration of AGE-treated HSF2 cells. We identified the NLRP3 inflammasome as a critical target of USP30 in AGE-induced functions. Mechanistically, we demonstrate that USP30 activates the NLRP3 inflammasome by deubiquitinating NLRP3. Finally, we show that inhibition of USP30 via MF-094 treatment facilitated wound healing in diabetic rats and resulted in decreased protein levels of NLRP3 and its downstream target caspase-1 p20, thus establishing the physiological importance of the identified USP30-NLRP3 link. Together, our findings suggest a therapeutic potential for USP30 in diabetic foot ulcers.

The effect of Buerger Allen exercise and the provision of oral vitamin C toward the improvement of peripheral tissue perfusion and healing of diabetic foot ulcers

To determine the effect of Buerger Allen exercise (BAE) and oral vitamin C provision toward the improvement of peripheral tissue perfusion and wound healing of diabetic foot ulcer (DFU). The research used quantitative methods with pre and post-experimental designs without control. The respondents in this study were 30 people with DFU in a Public Health Center, Barru, Eastern Indonesia. Our independent variables were Burger Allen exercise (BAE) and oral vitamin C provision. Meanwhile, the dependent variable is peripheral tissue perfusion, which evaluates by the Ankle Brachial Index (ABI) and wound healing using a diabetic foot ulcer assessment score (DFUAS). Participants allocated into three groups (BAE, Ester C, and BAE+Ester C). The ABPI value significantly increase in the BAE group ( p :0.010), and BAE+Ester C ( p :0.013) in day 14. Meanwhile, the DFUAS score also significantly improve at BAE group ( p :0.024), and BAE+Ester C ( p :0.001). BAE combined with oral vitamin C can improve peripheral tissue perfusion and accelerate wound healing of DFU.