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Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm 2 ), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm 2 ), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice. The treatment of infected diabetic wounds faces obstacles of bacterial infection, hypoxia, hyperexpression of reactive oxygen species, and inflammation. Here, the authors address these issues by developing a programmed treatment strategy that utilizes live Haematococcus to promote healing of diabetic wounds in a comprehensive manner.

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus -infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1 −/− mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs. Therapies for treating bacterial infection and increasing wound healing are needed. Here the authors report a liposozyme that combines reactive oxygen species generation and scavenging for antibacterial action and modulation of redox and immune homeostasis, increasing wound healing.

There are many factors involved in wound healing, and the healing process is not static. The therapeutic effect of modern wound dressings in the clinical management of wounds is documented. However, there are few reports regarding the reasonable selection of dressings for certain types of wounds in the clinic. In this article, we retrospect the history of wound dressing development and the classification of modern wound dressings. In addition, the pros and cons of mainstream modern wound dressings for the healing of different wounds, such as diabetic foot ulcers, pressure ulcers, burns and scalds, and chronic leg ulcers, as well as the physiological mechanisms involved in wound healing are summarized. This article provides a clinical guideline for selecting suitable wound dressings according to the types of wounds.

Diabetic foot problems are widespread globally, resulting in substantial medical, economic, and social challenges for patients and their families. Among diabetic complications, foot ulceration is the most frequent outcome and is more probable to be of neuropathic origin. To date, a plethora of studies has focused on diabetic foot and ulcer prevention. However, limited studies have investigated the biomechanics of diabetic foot post ulceration. In this work, extensive biomechanical modelling of diabetic foot ulcers was attempted. A full-scale foot model was developed using measurements from a human subject, and ulcers of differing sizes and depths were modelled at different plantar sites numerically. Also, the foot model was computationally modified to study the effect of flat foot conditions on the same diabetic ulcers. Standing condition was simulated, and the induced stresses were investigated at the plantar region. The maximum stresses were observed to be similar for all ulcer sizes and depths at the lateral midfoot region of the normal foot. However, the maximum stresses were reported in the lateral heel region for the flat foot, which varied significantly with size and depth. Such results present important information on the foot condition post ulceration and may help identify possibilities of further ulceration in the diabetic foot. These novel findings are anticipated to be indispensable for the development of suitable interventions (e.g., custom orthotics) for diabetic foot ulcer management.

Delayed wound healing can cause significant issues for immobile and ageing individuals as well as those living with co-morbid conditions such as diabetes, cardiovascular disease, and cancer. These delays increase a patient’s risk for infection and, in severe cases, can result in the formation of chronic, non-healing ulcers (e.g., diabetic foot ulcers, surgical site infections, pressure ulcers and venous leg ulcers). Chronic wounds are very difficult and expensive to treat and there is an urgent need to develop more effective therapeutics that restore healing processes. Sustained innate immune activation and inflammation are common features observed across most chronic wound types. However, the factors driving this activation remain incompletely understood. Emerging evidence suggests that the composition and structure of the wound microbiome may play a central role in driving this dysregulated activation but the cellular and molecular mechanisms underlying these processes require further investigation. In this review, we will discuss the current literature on: 1) how bacterial populations and biofilms contribute to chronic wound formation, 2) the role of bacteria and biofilms in driving dysfunctional innate immune responses in chronic wounds, and 3) therapeutics currently available (or underdevelopment) that target bacteria-innate immune interactions to improve healing. We will also discuss potential issues in studying the complexity of immune-biofilm interactions in chronic wounds and explore future areas of investigation for the field.

Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines. However, many patients experience minimal benefits from certain medical treatments because of poor compliance, short retention times in the oral cavity, and inadequate drug efficacy. Herein, we present a novel hydrogel patch (SCE2) composed of a biopolymer matrix (featuring ultraviolet-triggered adhesion properties) loaded with cuttlefish ink nanoparticles (possessing pro-healing functions). Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light. SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species. These properties contribute to the elimination of bacteria and the management of the oxidation process, thus accelerating the healing phase's progression from inflammation to proliferation. In studies involving diabetic rats with oral ulcers, the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area, facilitating rapid re-epithelialization, and fostering angiogenesis. In conclusion, this light-sensitive hydrogel patch offers a promising path to expedited wound healing, potentially transforming treatment strategies for clinical oral ulcers. We present a hydrogel patch (SCE2) endowed with strong adhesive properties and immunomodulatory functions, designed for the treatment of oral ulcers in diabetes. [Display omitted] •A hydrogel patch (SCE2) is engineered for treating oral ulcers in individuals with diabetes.•SCE2 is produced through the incorporation of cuttlefish ink nanoparticles within a biopolymer matrix.•SCE2 demonstrates potent capabilities in photothermal antibacterial and ROS scavenging.•SCE2 aids in the recovery of oral ulcers by diminishing inflammation and enhancing angiogenesis.

The healing process of diabetic foot ulcers (DFU) is associated with the risk of life-threatening complications. The aim of the study was to establish the most important risk factors which have an impact on the healing process. The retrospective analysis was conducted on patients with diagnosed T2DM and newly diagnosed DFU. The observation lasted 12 months and the primary outcome was complete healing of the wounds, the secondary outcome was defined as a need for vascular intervention of the lower extremity (VI) or the occurrence of a new wound (NW). The data examined with a chi2 test analysis of the odds ratio in the SAS 9.4 program. 64 patients cases (13 women and 51 men) with mean weight (101.48kgs (±22.4)), age (60.59 years old (±9.14)) were analyzed. The mean baseline area of the patient's wounds was 7.75cm2 (±16.46). The primary outcome was achieved by 42.19% (n=27). The NW occurred among 39.06% (n=25), and 21.88% (n=14) needed VI. The patients with the area of all wounds bigger than 5cm2 have a higher risk of having unhealed wounds (OR=7.58, p<0.05). Additionally, diagnosed anemia or cigarette smoking on the first visit was associated with a higher risk of NW (OR=9.5, p<0.05 and OR=3.8, p<0.05). None of the analyzed factors had an impact on the risk of VI. The simple characterization of wounds and patients can be useful in estimating of risk of having an unhealed wound or the occurrence of a new wound 12 months after the first visit.

Therapeutic footwear becomes the first treatment line in the prevention of diabetic foot ulcer and future complications of diabetes. Previous studies and the International Working Group on the Diabetic Foot have described therapeutic footwear as a protective factor to reduce the risk of re-ulceration. In this study, we aimed to analyze the efficacy of a rigid rocker sole to reduce the recurrence rate of plantar ulcers in patients with diabetic foot. Between June 2016 and December 2017, we conducted a randomized controlled trial in a specialized diabetic foot unit. Fifty-one patients with diabetic neuropathy who had a recently healed plantar ulcer were randomized consecutively into the following two groups: therapeutic footwear with semi-rigid sole (control) or therapeutic footwear with a rigid rocker sole (experimental). All patients included in the study were followed up for 6 months (one visit each 30 ± 2 days) or until the development of a recurrence event. Primary outcome measure was recurrence of ulcers in the plantar aspect of the foot. A total of 51 patients were randomized to the control and experimental groups. The median follow-up time was 26 [IQR-4.4-26.1] weeks for both groups. On an intention-to-treat basis, 16 (64%) and 6 (23%) patients in the control and experimental groups had ulcer recurrence, respectively. Among the group with >60% adherence to therapeutic footwear, multivariate analysis showed that the rigid rocker sole improved ulcer recurrence-free survival time in diabetes patients with polyneuropathy and DFU history (P = 0.019; 95% confidence interval, 0.086-0.807; hazard ratio, 0.263). We recommend the use of therapeutic footwear with a rigid rocker sole in patients with diabetes with polyneuropathy and history of diabetic foot ulcer to reduce the risk of plantar ulcer recurrence. ClinicalTrials.gov NCT02995863.

Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes, presenting as open sores or wounds on the sole. They result from impaired blood circulation and neuropathy associated with diabetes, increasing the risk of severe infections and even amputations if untreated. Early detection, effective wound care, and diabetes management are crucial to prevent and treat DFUs. Artificial intelligence (AI), particularly through deep learning, has revolutionized DFU diagnosis and treatment. This work introduces the DFU_XAI framework to enhance the interpretability of deep learning models for DFU labeling and localization, ensuring clinical relevance. The framework evaluates six advanced models—Xception, DenseNet121, ResNet50, InceptionV3, MobileNetV2, and Siamese Neural Network (SNN)—using interpretability techniques like SHAP, LIME, and Grad-CAM. Among these, the SNN model excelled with 98.76% accuracy, 99.3% precision, 97.7% recall, 98.5% F1-score, and 98.6% AUC. Grad-CAM heat maps effectively identified ulcer locations, aiding clinicians with precise and visually interpretable insights. The DFU_XAI framework integrates explainability into AI-driven healthcare, enhancing trust and usability in clinical settings. This approach addresses challenges of transparency in AI for DFU management, offering reliable and efficient solutions to this critical healthcare issue. Traditional DFU methods are labor-intensive and costly, highlighting the transformative potential of AI-driven systems.

Diabetic foot ulcers impose significant financial burdens and diminished quality of life. Effective management relies on patients' self-care, yet often overlooked by patients as neuropathic feet are painless. In Malaysia, primary care facilities focus on prevention by promoting proper foot self-care. However, the lack of a standardised assessment tool hampers nationwide evaluation. This paper outlines the methodology for developing and validating an instrument tailored to the Malaysian context to assess diabetic foot self-care practices. A structured methodological process will be employed to guide the instrument's development and subsequent validation. The instrument aims to encompass comprehensible questions with a simple scoring and interpretation mechanism to foster its daily use. The study will consist of two phases. Phase 1 focuses on the development of the Malaysian instrument. This phase encompasses a literature review, item development tailored to the Malaysian context, content validity through expert panel evaluations, translations, pre-tests and a follow-up stakeholder engagement to ensure the instrument meets their requirements. Incorporating perspectives from experts and comprehensibility by local patients ensures the instrument's relevance to the local context. Phase 2 involves instrument validation through a cross-sectional study. This phase entails a pilot test and field test of the instrument among diabetic patients for validation. Cut-off ranges and their interpretations will also be established in this phase. The study sites encompass a mix of urban and rural public health clinics across Peninsular as well as East Malaysia. By developing a standard validated instrument to assess diabetic foot self-care practices, services provision gaps can be identified, and targeted interventions to improve these gaps in practices can be implemented. Individually tailored diabetes foot care education is crucial in preventing foot ulcers. This instrument can also facilitate the monitoring of improvements in patients' foot self-care practices longitudinally.