Diabetic foot ulcers (DFU) represent one of the most common side effects of diabetes, significantly impacting patients' quality of life and imposing considerable financial burdens on families and society at large. Despite advancements in therapies targeting lower limb revascularization and various medications and dressings, outcomes for patients with severe lesions remain limited. A recent breakthrough in DFU treatment stems from the development of mesenchymal stem cells (MSCs). MSCs have shown promising results in treating various diseases and skin wounds due to their ability for multidirectional differentiation and immunomodulation. Recent studies highlight that MSCs primarily repair tissue through their paracrine activities, with exosomes playing a crucial role as the main biologically active components. These exosomes transport proteins, mRNA, DNA, and other substances, facilitating DFU treatment through immunomodulation, antioxidant effects, angiogenesis promotion, endothelial cell migration and proliferation, and collagen remodeling. Mesenchymal stem cell-derived exosomes (MSC-Exo) not only deliver comparable therapeutic effects to MSCs but also mitigate adverse reactions like immune rejection associated with MSCs transplantation. This article provides an overview of DFU pathophysiology and explores the mechanisms and research progress of MSC-Exo in DFU therapy.

Low-extremity ischemic disease is a common complication in diabetic patients, leading to reduced quality of life and potential amputation. This study investigated the therapeutic effect of spinal cord stimulation (SCS) on patients with diabetic foot disease and a rat model of diabetic foot injury. SCS was applied to patients with diabetic foot disease, with clinical assessments performed before and after therapy. Blood levels of NGF, BDNF, and NT-3 were determined by ELISA. A rat model of diabetic foot injury was established to validate NT-3's role in SCS therapy. SCS therapy improved the condition of patients with diabetic ischemic foot disease and promoted wound healing in the rat model. NT-3 levels significantly increased after SCS therapy in both patients and rats. Recombinant NT-3 administration improved wound healing and re-vascularization in the rat model, while NT-3 neutralization abrogated SCS's therapeutic effect. SCS improves the condition of patients with diabetic ischemic foot disease by inducing NT-3 production. Both SCS and NT-3 supplementation show therapeutic potential for ameliorating diabetic foot disease.

To develop a concise screening tool for diabetic foot risk assessment in patients with diabetes, and rigorously evaluate its reliability and validity.

390 adults diagnosed with diabetes were selected for a study in Changsha, China. The study was conducted in two phases. In the first phase, initial items were developed by amalgamating existing diabetic foot risk screening tools and group discussions. Additionally, diabetic foot experts established content validity during this phase. In the second phase, the validity and reliability of the developed items were evaluated through various methods such as item analysis, exploratory factor analysis, confirmatory factor analysis, Cronbach's alpha coefficient, retest reliability, inter-rater reliability, ROC curve and AUC.

The Brief Diabetic Foot Risk Screening Scale consists of 6 dimensions and 19 items. An exploratory factor analysis was conducted on the scale, revealing six principal factors that accounted for 74.139 % of the total variance. The I-CVI was greater than 0.8, indicating good content validity, while the S-CVI was 0.737. Confirmatory factor analysis showed that the model fit well. The scale's Cronbach's α coefficient was 0.770, indicating good internal consistency, and its test-retest reliability was 0.958. The AUC suggests that the Brief Diabetic Foot Risk Screening Scale is an effective measure for identifying diabetic foot.

The Scale is a reliable and valid tool for assessing foot risk.

Background/Objectives: Diabetic foot ulcers (DFUs) are a common and severe complication of diabetic patients, with significant global prevalence and associated health burdens, including high recurrence rates, lower-limb amputations, and substantial associated economic costs. This study aimed to understand the user needs of healthcare professionals treating diabetic foot ulcers for newly developed material technologies. Methods: An open-ended questionnaire was used to identify user needs, identify the limitations of current treatments, and determine the specific requirements for ideal treatment. This information was used to develop a list of key considerations for creating innovative material technologies to improve diabetic wound treatment results. Results: Most respondents indicated that they followed published treatment guidelines for DFUs but noted that treatment often required a case-specific approach. Antibiotics and surgical debridement were commonly used for infection control. The participants showed a strong preference for wound dressings with lasting antibacterial properties. Respondents identified ideal properties for new products, including ease of use, enhanced antibacterial properties, affordability, and targeted biological activity. The respondents also highlighted the importance of a holistic approach to DFU management, integrating product development with comprehensive care strategies and patient education. Conclusions: This study highlights the complexity of DFU care, emphasizing that no single product can address all treatment needs. Future materials could focus on combination therapies and specific use cases. Additionally, understanding global variations in treatment practices and educating users on the proper application of newly developed material technologies is crucial for improving the management of DFUs and patient outcomes.

The number of patients with diabetes mellitus (DM) has been progressively increasing worldwide over the past decades, and many international organizations consider DM as a public health emergency of the 21st century.Critical limb ischemia (CLI) is the most severe stage of peripheral arterial disease (PAD) in DM and is characterized by a high risk of limb loss without revascularization. Traditional treatment tactics include open and endovascular revascularization surgical techniques. However, in patients not eligible for revascularization and in cases where performed surgical treatment performed has been ineffective, there are almost no therapeutic alternatives, often leading to amputations and death. As of today, one of the newest non-surgical treatment options is cell therapy. Among different cells, mesenchymal stromal cells (MSCs) are potentially one of the most prospective for use in this patient population.This article provides an overview of clinical trials using cell therapy in patients with CLI.To analyze publications, electronic databases PubMed, SCOPUS, ClinicalTrials, and ScienceDirect were searched to identify published data from clinical trials, research studies, and review articles on cell therapy for critical lower extremity ischemia. After the search, 489 results were received.As a result of systematic selection, 22 clinical trials were analyzed.According to the analyzed literature data, the use of cell products in this category of patients is effective and safe. Cell therapy can stimulate the formation of new vessels and enhances collateral circulation; it is also reported improved distal perfusion, increased pain-free walking distance, decreased amputation rates, and increased survival rates.Nevertheless, further study of the potential use of this category of drugs is needed.

The diabetic foot interacts with anatomical, vascular, and neurological factors that challenge clinical practice. This study aimed to compile the primary scientific evidence based on a review of the main guidelines, in addition to articles published on the Embase, Lilacs, and PubMed platforms. The European Society of Cardiology system was used to develop recommendation classes and levels of evidence. The themes were divided into six chapters (Chapter 1 - Prevention of foot ulcers in people with diabetes; Chapter 2 - Pressure relief from foot ulcers in people with diabetes; Chapter 3 -Classifications of diabetic foot ulcers; Chapter 4 - Foot and peripheral artery disease; Chapter 5 - Infection and the diabetic foot; Chapter 6 - Charcot's neuroarthropathy). This version of the Diabetic Foot Guidelines presents essential recommendations for the prevention, diagnosis, treatment, and follow-up of patients with diabetic foot, offering an objective guide for medical practice.

The onset of diabetes mellitus (DM), a metabolic disorder characterized by high blood glucose levels and disrupted glucose metabolism, results in 20% of people with diabetes suffering from diabetes-related wounds worldwide. A minor wound, such as a cut or abrasion, can lead to infections and complications in diabetic patients. We must understand the mechanism/s contributing to this delayed wound healing to develop effective prevention strategies. The potential benefits of bioactive phytochemicals for diabetic wound healing have been reported in numerous studies.

A bioactive compound may have multiple actions, including antioxidants, antiinflammatory, antimicrobial, and angiogenesis. Compounds derived from these plants have shown promising results in wound healing, inflammation reduction, collagen synthesis, and neovascularization improvement.

Consequently, this review provides an update to our understanding of how phytoconstituents promote wound healing in diabetics. A thorough literature review was conducted on diabetes, wound healing, and phytoconstituents for this study. Only English publications until June 2023 were included in the search, which used multiple search engines and the main keywords. Summing up, phytochemical-based interventions might improve the quality of life for diabetics by improving wound healing.

However, to fully understand the efficacy and safety of these phytochemicals in managing diabetic wounds, more research and clinical trials are needed.

Over the past years, the development of innovative smart wound dressings is revolutionizing wound care management and research. Specifically, in the treatment of diabetic foot wounds, three-dimensional (3D) bioprinted patches may enable personalized medicine therapies. In the present work, a methacrylated hyaluronic acid (MeHA) bioink is employed to manufacture 3D printed patches to deliver small extracellular vesicles (sEVs) obtained from human mesenchymal stem cells (MSC-sEVs). The production of sEVs is maximized culturing MSCs in bioreactor. A series of in vitro analyses are carried out to demonstrate the influence of MSC-sEVs on functions of dermal fibroblasts and endothelial cells, which are the primary functional cells in skin repair process. Results demonstrate that both cell populations are able to internalize MSC-sEVs and that the exposure to sEVs stimulates proliferation and migration. In vivo experiments in a well-established diabetic mouse model of pressure ulcer confirm the regenerative properties of MSC-sEVs. The MeHA patch enhances the effectiveness of sEVs by enabling controlled release of MSC-sEVs over 7 days, which improve wound epithelialization, angiogenesis and innervation. The overall findings highlight that MSC-sEVs loading in 3D printed biomaterials represents a powerful technique, which can improve the translational potential of parental stem cell in terms of regulatory and economic impact.

Despite clear evidence of inadequate angiogenesis in ischemic diabetic foot syndrome (DFS) pathogenesis, angiogenic factor level changes in patients with ischemic DFS remain inconsistent. This study aimed to assess circulating angiogenic factors concerning ischemic DFS advancement and describe their relationships with patients' clinical characteristics, microvascular parameters, and diabetic control. The study included 41 patients with ischemic DFS (67.3 (8.84) years; 82.9% males). Angiogenic processes were assessed by identifying circulating concentrations of five pro- and two anti-angiogenic factors. We found that penetrating ulcers were related to a significantly higher FGF-2 level (8.86 (5.29) vs. 5.23 (4.17) pg/mL, p = 0.02). Moreover, plasma FGF-2 showed a significant correlation with the SINBAD score (r = 0.32, p = 0.04), platelet count (r = 0.43, p < 0.01), white cell count (r = 0.42, p < 0.01), and age (r = -0.35, p = 0.03). We did not observe any significant linear relationship between the studied biomarkers and microcirculatory parameters, nor for glycemic control. In a univariate analysis using logistic regression, an increase in plasma FGF-2 was tied to greater odds of high-grade ulcers (OR 1.16; 95% CI 1.02-1.38, p = 0.043). This suggests that circulating FGF-2 may serve as a potential biomarker for predicting DFU advancement and progression. It is necessary to conduct further studies with follow-up observations to confirm this hypothesis.

digital variance angiography (DVA) provides higher image quality than digital subtraction angiography (DSA). This study investigates whether the quality reserve of DVA allows for radiation dose reduction during lower limb angiography (LLA), and compares the performance of two DVA algorithms.

this prospective block-randomized controlled study enrolled 114 peripheral arterial disease patients undergoing LLA into normal dose (ND, 1.2 µGy/frame, n = 57) or low-dose (LD, 0.36 µGy/frame, n = 57) groups. DSA images were generated in both groups, DVA1 and DVA2 images were generated in the LD group. Total and DSA-related radiation dose area product (DAP) were analyzed. Image quality was assessed on a 5-grade Likert scale by six readers.

the total and DSA-related DAP were reduced by 38% and 61% in the LD group. The overall visual evaluation scores (median (IQR)) of LD-DSA (3.50 (1.17)) were significantly lower than the ND-DSA scores (3.83 (1.00), p < 0.001). There was no difference between ND-DSA and LD-DVA1 (3.83 (1.17)), but the LD-DVA2 scores were significantly higher (4.00 (0.83), p < 0.01). The difference between LD-DVA2 and LD-DVA1 was also significant (p < 0.001).

DVA significantly reduced the total and DSA-related radiation dose in LLA, without affecting the image quality. LD-DVA2 images outperformed LD-DVA1, therefore DVA2 might be especially beneficial in lower limb interventions.

Diabetic foot ulcer (DFU) is considered the most catastrophic complication of diabetes mellitus (DM), leading to repeated hospitalizations, infection, gangrene, and finally amputation of the limb. In patients suffering from diabetes mellitus, the wound-healing process is impaired due to various factors such as endothelial dysfunction and synthesis of advanced glycation end-products, hence, conventional therapeutic interventions might not be effective. With increasing therapeutic applications of mesenchymal stem cells (MSCs) in recent years, their potential as a method for improving the wound-healing process has gained remarkable attention. In this field, mesenchymal stem cells exert their beneficial effects through immunomodulation, differentiation into the essential cells at the site of ulcers, and promoting angiogenesis, among others. In this article, we review cellular and molecular pathways through which mesenchymal stem cell therapy reinforces the healing process in non-healing Diabetic foot ulcers.

Diabetic foot complications represent a substantial health burden and are the foremost cause of hospitalization in patients with diabetes. Diabetes mellitus (DM) is known to cause several other problems. Diabetes is rapidly becoming the leading cause of illness and death worldwide. Diabetic foot ulcers (DFU) are one of the most painful complications of diabetes. These complications cause problems in blood vessels, nerves, and other organs throughout the body. DFU pathophysiology is attributed to a triad of neuropathies, trauma with secondary infection, and arterial occlusive disease. This review aims to identify the types of wounds that diabetics can develop. Owing to the complexity of their disease pathology, diabetics are susceptible to a variety of wounds, such as diabetic ulcers due to trauma (DUDT); neuropathic, ischemic, neuroischemic, arterial, venous, and mixed wounds; and diabetic bullae, furuncles, cellulitis, and carbuncles. Therefore, it is essential for healthcare providers to recognize the specific classification of a diabetic wound based on its distinctive attributes to provide appropriate wound care and therapeutic interventions. In the context of individuals with diabetes, it is of paramount significance to precisely identify the types of wounds during the initial evaluation to provide appropriate care and treatment, thereby enhancing the probability of favorable outcomes.