Search Results (874)

Background: There is a positive relationship between mitochondrial damage in the cell and uptake in technetium Tc 99m monomer methoxy isobutyl isonitrile (^99mTc-MIBI) scintigraphy. Severe mitochondrial dysfunction with cell death occurs in patients with diabetic foot ulcers (DFUs). To decide on the level of amputation, ^99mTc-MIBI scintigraphy should be considered. Methods: Prospectively, 24 patients with DFUs were included in the study. Based on treatment that started with the hospitalization, patients were divided into two groups: those whose DFUs healed and did not need surgical intervention (healed group) and those whose DFUs did not regress despite surgical and medical treatment and who required further surgical intervention (reoperation group). Before surgery, ^99mTc-MIBI scintigraphy was performed. The ^99mTc-MIBI uptake rates of the injured foot relative to the healthy foot were recorded. Deep-tissue culture was taken at surgery. Erythrocyte sedimentation rate, white blood cell count, and C-reactive protein (CRP) and albumin levels were measured. Results: The ^99mTc-MIBI uptake rates of patients with poor prognosis were higher at all times than those of patients who did not require revision surgery. A significant difference was found between these values in the 10 and 30 s rates. The mean ± SD CRP level was 86.04 ± 21.87 mg/dL in the healed group and 144.43 ± 27.54 mg/dL in the reoperation group (p = 0.040). There was a positive correlation between ulcerated foot and healthy foot ^99mTc-MIBI involvement rates at 10 and 30 s and CRP values, and a negative correlation between albumin values. Conclusions: There was a significant relationship between ^99mTc-MIBI involvement rates and poor prognosis and reamputation. The correlation between CRP and albumin levels, which are among the predictive values, and ^99mTc-MIBI uptake confirmed this relationship in DFUs, which are difficult to manage and treat. Full article

The Therapeutic Shoe Benefit (TSB) allows Medicare insurance beneficiaries to reduce their diabetic foot ulcer risk by providing offloading shoes. Anecdotal evidence suggests that the process is cumbersome and that not all providers are aware of this benefit. This study evaluated TSB awareness across multiple healthcare disciplines and documented barriers to utilization. An online study surveyed healthcare providers practicing in the United States to determine familiarity with TSB and barriers to prescribing therapeutic shoes. The project was IRB-reviewed and received exempt status. The survey was sent to a wide variety of healthcare practitioners including: podiatrists, primary care providers, physical therapists, orthotist/prosthetists, specialty providers, and diabetes educators. This was done through targeted emails from professional organizations, word-of-mouth messaging through private practice groups, and marketing on LinkedIn. The survey was administered via Qualtrics with embedded branching logic used to gather data from the TSB’s three classifications of healthcare specialists: certifying physicians, prescribing practitioners, and suppliers. A total of 580 valid completions of the survey were analyzed. Irrespective of the TSB, podiatric physicians and medical professionals providing direct patient care recommend supportive shoes for patients with diabetes 98.2% (336/342) of the time. When asked about knowledge of the TSB, 522 or 90% of respondents indicated awareness of this Medicare benefit. Knowledge by specialty was hard to differentiate due to low responses by some specialties; however, prescribing podiatrists and prosthetic providers both responded with a familiarity rate above 92%. Common obstacles to providers prescribing shoes were: complexity of documentation (67.8%), challenges communicating with other providers (55.0%), and financial reasons/labor-to-reimbursement ratio (38.4%). TSB has the potential to reduce amputations and wound care costs. However, therapeutic shoes are underutilized with less than 20% of potential beneficiaries accessing this benefit. This research strengthens the argument that streamlining the process may increase access to therapeutic shoes. Full article

Background: Diabetic foot ulcers (DFUs) are difficult to heal because hyperglycemia-associated pathological exudation, excessive oxidative stress, chronic inflammation, and impaired cellular regeneration jointly maintain a nonhealing wound microenvironment. This study aimed to develop and evaluate a composite hydrogel containing Periplaneta americana (PA) extract and calamine as a Zn²⁺ source for dynamic modulation of the diabetic wound microenvironment and promotion of tissue repair. Methods: A PA composite hydrogel was prepared and assessed in vitro for reactive oxygen species (ROS)-scavenging activity and effects on fibroblast migration. Therapeutic efficacy was further evaluated in a streptozotocin (STZ)-induced diabetic full-thickness wound model in rats. Wound closure, histological remodeling, oxidative stress markers, inflammatory mediators, growth factors, angiogenesis, and AGEs-RAGE/NF-κB pathway-related changes were analyzed. Results: The composite hydrogel reduced excessive intracellular ROS and enhanced fibroblast migration in vitro compared with pathological-condition controls. In diabetic rats, topical treatment accelerated macroscopic wound closure and promoted more mature histological repair. Mechanistic analyses showed attenuation of the AGEs-RAGE/NF-κB signaling axis, accompanied by restoration of superoxide dismutase activity, reduction of malondialdehyde levels, and suppression of TNF-α-associated inflammatory responses. The improved wound microenvironment was associated with increased expression of platelet-derived growth factor and basic fibroblast growth factor, enhanced cellular proliferation, and increased neovascularization within the wound tissue. Conclusions: The PA composite hydrogel improved diabetic wound healing by concurrently alleviating oxidative and inflammatory barriers and enhancing regenerative signaling. These findings suggest that microenvironment-modulating PA composite hydrogel systems may represent a promising therapeutic strategy for refractory diabetic wounds. Full article

Background: Growth factor therapy often fails in diabetic foot ulcers (DFUs). The reason remains unclear. Standard differential expression analysis may miss functionally critical genes with modest expression changes. Methods: We performed a secondary computational analysis of a longitudinal DFU transcriptomic dataset (Dryad; 17 patients, 117 serial biopsy samples, 12-week follow-up). Co-expression networks were built separately for healed (n = 37) and non-healed (n = 80) samples. Virtual gene knockout (VGK) was used to rank genes by topological impact on network cohesion. Single-cell analysis (GSE165816) assessed the association between endogenous KIF13A expression and keratinocyte migration-related signatures. A conceptual Hill-equation simulation was used to illustrate the transport-signaling threshold relationship. Drug repurposing used DSigDB enrichment. An independent bulk DFU cohort (GSE134431) was used for external validation. Results: KIF13A showed no differential expression (log₂FC = 0.173, p = 0.263) yet ranked first by VGK topological impact. In keratinocytes, high KIF13A expression correlated with greater migration scores versus zero-detection cells (p = 0.0058). A clear threshold effect emerged: below the 30th expression percentile, EGF, PDGF, and FGF pathway activation scores remained near baseline. In a structural-equation model, transport activity negatively predicted inflammation (standardized β = −0.92, p < 0.001). HIF1A showed the strongest positive correlation with KIF13A in keratinocytes (Spearman ρ = 0.26, p < 0.001), and FOS showed a negative correlation in the single-cell analysis (ρ = −0.16, p < 0.001) and in the bulk longitudinal cohort (ρ = −0.32, p < 0.001, n = 117). Recurrent AKR1B1-related drug signatures nominated the aldose-reductase pathway, and epalrestat was therefore prioritized as a hypothesis-generating candidate compound rather than a direct top-ranked enrichment hit. External validation confirmed consistent upregulation of KIF13A (Fold-Change = 1.58, adj. p = 0.0075), EPN1, and CLIP1 in DFU tissue. Despite population-level upregulation, a subset of cells fell below the functional signaling threshold. Conclusions: These computational findings suggest that KIF13A-associated vesicle transport impairment may represent a candidate systems-level bottleneck for growth-factor responsiveness in DFUs, a network-level pattern not captured by standard differential-expression analysis. Epalrestat, an AKR1B1 inhibitor prioritized through recurrent AKR1B1-related drug signatures, is presented as a candidate compound for further evaluation. As the present analysis is observational and computational, the findings should be interpreted as hypothesis-generating; experimental perturbation studies and prospective clinical validation are required. Full article

Aims: The purpose of this study was to clarify the prevalence of diabetic foot lesions and their association with lower-limb amputations and/or foot ulcers. Materials and Methods: In this cross-sectional study, 968 patients with diabetes were surveyed. Diabetic foot lesions were defined according to the broad national criteria, which encompass both mild abnormalities and more advanced conditions. Based on this definition, foot lesions were assessed using a questionnaire comprising the following 10 items: a history of lower-limb amputations, a history of treatment of foot lesions, numbness/loss of sensation/pain, skin discolorations, skin symptoms, nail abnormalities, foot ulcers/gangrene, foot deformities, foot infection, and intermittent claudication. Logistic regression analysis was used to examine risk factors for foot lesions. Area under the curve (AUC) of the number of foot lesions for lower-limb amputations or foot ulcers/gangrene was calculated using the receiver operating characteristic curve (ROC) analysis. Results: Approximately two-thirds of the patients had at least one type of diabetic foot lesion. Logistic regression analysis revealed that women, past or current smoking, a history of cardiovascular disease, and nephropathy were associated with the risk of diabetic foot lesions. According to the ROC analysis, the optimal cut-off point of number of diabetic foot lesions was three for identifying patients with a history of lower-limb amputation and/or the presence of foot ulcers or gangrene (AUC 0.80 (95% CI, 0.70–0.91), p < 0.01). Conclusions: Diabetic foot lesions are common in patients with diabetes and the prevalence of diabetic foot lesions was higher in patients with a history of lower-limb amputations and/or the presence of foot ulcers or gangrene. Early detection and care of diabetic foot lesions are necessary to prevent lower-limb amputations and foot ulcers. Full article

Background: Smart offloading technologies enable the real-time, objective monitoring of adherence in patients with diabetic foot ulcers (DFUs). Although remote tracking may reinforce adherence and improve wound healing, effectiveness depends on sustained device use, particularly as devices are often removed during rest periods. Real-time, behavior-contingent feedback informed by sensor data, including AI-supported messaging capable of detecting nonadherence, may enhance reinforcement. However, the feasibility and behavioral impact of such strategies remain unclear. Methods: We conducted a prospective feasibility case series nested within a larger DFU cohort of 210 participants, enrolling eight adults with active DFUs. Participants used a sensor-integrated offloading device paired with a smartwatch (SmartBoot) and a mobile application (CORA) that delivered notifications to their smartphones. Notifications were either schedule-based or context-aware, using real-time SmartBoot data to generate personalized messages. The primary outcome was a sensor-detected transition from nonadherent to adherent offloading within 60 min. Results: A total of 130 notifications were delivered, with 125 included in the behavioral response analysis. Context-aware notifications demonstrated higher transition rates than schedule-based notifications. Adaptive Reinforcement yielded the highest response rate (77.4%, 24/31), followed by Clinical Course Correction (71.4%, 20/28), whereas Safety and Technical Assurance (40.7%, 11/27) and Motivational Coaching (30.8%, 12/39) showed lower response rates. Conclusions: Real-time, context-aware feedback is feasible and associated with improved short-term adherence, supporting evaluation in larger trials. Full article

Background: Diabetic Foot Ulcers (DFU) are a common complication of diabetes, often leading to infections, amputations and even death if left untreated. Effective management of the Diabetic Foot (DF) requires timely detection and frequent monitoring. Current DF assessment methods, by healthcare professionals, are largely based on visual inspection of feet, together with touch, temperature, and vibration sensitivity, and pedal pulse. Methods: The paper describes a machine-learning approach for the assessment of DF from feet images, combining pre-trained convolutional neural networks (CNN) with Generative AI for dataset annotation. Specifically, the GPT-4o-mini model was used to assign risk labels (Low, Medium or High Risk) to individual foot images, following a structured designed prompt for this task. The labeled dataset was used to train and evaluate two pre-trained CNN architectures, namely, ResNet50 and VGG16. Output predictions are obtained by aggregating the prediction for each of the images of a patient. Results: The results obtained show that both ResNet50 and VGG16 achieved good overall performance, with ResNet50 showing superior results. The High Risk class achieved the highest performance. The Low and Medium Risk classes also showed good performance but were prone to confusion due to the similar features of the images belonging to those classes. Conclusions: The technical contribution of the paper is a Streamlit App, available online for public use, showcases the work. The primary scientific contribution is the demonstration of how Generative AI can be used to train common CNN and automate a highly relevant healthcare process. Full article

Background: Diabetic neuropathy is one of the most common chronic complications of diabetes mellitus and could lead to foot ulcerations, lower-limb amputations, increased mortality and reduced quality of life. This study examines the level of GPIHBP1 to assess its diagnostic and prognostic values across the metabolic continuum. Methods: This is an observational monocentric study, including 160 patients with type 2 diabetes mellitus, obesity without carbohydrate metabolism disorders and healthy controls. Clinical data and laboratory results were collected, and serum levels of GPIHBP1 were measured using an ELISA. The presence of DPN for the diabetes group was assessed using corneal confocal microscopy and NDS. The statistical analyses included t-tests, Pearson’s correlation analysis, and ROC analysis to explore associations and the predictive values of the biomarker. Results: The GPIHBP1 levels increased progressively, with the lowest levels observed in the control group, higher levels in patients with obesity, and the highest levels in those with diabetes mellitus. Higher GPIHBP1 levels were observed in patients with peripheral diabetic neuropathy compared to those without. GPIHBP1 demonstrated moderate discriminative performance for the presence of diabetes, diabetic neuropathy and nephropathy. GPIHBP1 levels were also associated with renal function parameters and markers of vascular involvement. After adjustment for confounders, including estimated glomerular filtration rate (eGFR), the association between GPIHBP1 and diabetic neuropathy remained statistically significant although attenuated. Higher levels were observed in patients with coronary artery disease, and a positive correlation was established with mean IMT and sudomotor dysfunction score. Conclusions: Circulating GPIHBP1 levels are associated with diabetes mellitus and its micro- and macrovascular complications, particularly diabetic neuropathy. Its measurement could enhance early diagnosis and personalized management of T2DM, and, while these findings support a potential role of GPIHBP1 as a biomarker of metabolic and vascular dysfunction, its clinical utility requires confirmation in longitudinal studies. Full article

Background: Effective communication with patients is vital for improving health outcomes in chronic disease management. In this study, we investigated WoundScribeAI’s Scribe AI, also known as Ambient Technology, and its patient education and engagement app, Pingoo.AI. It employed a multi-agent AI model that leveraged Large Language Models (LLMs) and NotebookLM to enhance patient communication in clinical settings. Methods: The system comprised specialized agents that transcribed healthcare provider–patient conversations through ambient dictation. This transcription generated medical notes that followed the Subjective, Objective, Assessment, and Plan (SOAP) format—a structured document used by healthcare providers to record and communicate information about patient encounters. Simultaneously, comprehensive visit summaries were also created. In the next step, these visit summaries were used to produce conversational and educational content by leveraging NotebookLM, an AI model introduced by Google that can generate podcast-style conversations from provided information. Integrating these agents allows clinicians to deliver engaging, empathetic, and actionable information to patients. Medical experts conducted a two-phase evaluation of the system’s performance based on multiple criteria, with a particular focus on diabetes education and diabetic foot care. The first phase used pre-recorded training videos, while the second phase involved simulated consultations by clinicians using the system. To validate the AI-generated educational content, we used several established frameworks in health communication that closely align with our enhancement goals. Results: The results showed that the AI model generated accurate clinical documentation and met the criteria for accurate SOAP Notes, visit summaries, and engaging educational content for patients. Given that hallucination is a significant concern related to large language models, especially in critical fields like healthcare, we meticulously analyzed the generated outputs to identify any signs of hallucinated information. Three outcomes successfully passed the validation criteria, including accuracy, completeness, comprehensiveness, absence of potential harm, and no hallucination. Additionally, the Conversational Education content was confirmed against established patient education frameworks and met criteria such as the use of metaphors, empathetic tone, and appropriate language, providing additional detail to help manage the condition. Conclusions: By providing specific instructions and prompts to NotebookLM to transform visit summaries into educational conversations, we significantly enhanced the comprehensiveness and engagement of the content for patients. In contrast to a traditional summary of the clinical visit, the podcast-style conversation enriched the content with background information, encouraging language, an empathetic tone, and helpful metaphors. Our analysis confirmed that the system did not exhibit any hallucinations, highlighting the effectiveness of our approach in mitigating this risk. These findings support the use of multi-agent AI models, combined with ambient dictation and tools like NotebookLM, to improve patient communication that surpasses traditional paper-based brochures, which are often impersonal, minimal, and do not always adhere to recommended factors for health literacy. Full article

The antimicrobial resistance crisis necessitates innovative systems for delivering oxidising agents. This study reports the development of a Carbopol^® 940 hydrogel functionalised with plasma-activated water (PAW) for the stabilisation and controlled release of reactive oxygen species (ROS). PAW was synthesised using a dielectric barrier discharge (DBD) reactor with continuous flow of water. The hydrogel’s architecture was characterised via SEM and FTIR, revealing a self-organised nanoporous structure (~1433 nm) that acts as a chemical reservoir. This architecture resulted in 100% retention of O₃ and H₂O₂ for 90 min, significantly extending the biological activity window compared with liquid PAW, and maintaining therapeutic concentrations (3 ppm of H₂O₂) beyond 45 h. In vitro antibacterial potency against Escherichia coli was validated, yielding a clear 25 mm inhibition zone. Subsequently, a clinical proof-of-concept was conducted in a patient with a recalcitrant Wagner Grade 2 diabetic foot ulcer (DFU). The hydrogel as monotherapy—without systemic antibiotics—achieved complete infection remission and full wound closure within 60 days. While this n = 1 case demonstrates translational feasibility, further validation through an ongoing controlled clinical trial is required. In conclusion, the PAW–Carbopol^® 940 hydrogel is a disruptive, low-cost therapeutic platform that effectively eradicates infection and promotes tissue repair through oxidative eustress, positioning it as a sustainable alternative for the advanced management of complex chronic wounds and regenerative medicine. Full article

Background: This study investigates a novel alginate–gelatin hydrogel incorporating polyphenol-rich grape skin extract as a multifunctional therapeutic system for diabetic wound healing. The extract was obtained by ultrasound-assisted extraction and formulated into a biopolymer hydrogel designed to combine optimal moisture retention with the controlled release of bioactive compounds. Methods: A streptozotocin-induced diabetic rat model was used to evaluate wound contraction, collagen deposition, oxidative stress parameters, and systemic inflammatory markers over a 15-day period. Animals were assigned to four groups: untreated control, silver sulfadiazine (SSD), empty hydrogel (EH), and extract-loaded hydrogel (LH). Results: The LH formulation demonstrated superior wound closure, reaching 97.1% by day 15, significantly outperforming SSD and other groups. Hydroxyproline levels were markedly elevated in LH-treated tissues, indicating enhanced collagen synthesis and extracellular matrix formation. Redox analyses revealed substantial reductions in TBARS and significant increases in SOD, CAT, and GSH, confirming the strong antioxidative activity of the incorporated extract. Moreover, LH treatment produced pronounced decreases in IL-6 and TNF-α, restoring inflammatory balance and facilitating timely progression from the inflammatory to proliferative phase. Conclusions: These effects are attributed to the synergistic actions of grape skin polyphenols which exerted broad biochemical and structural benefits essential for diabetic wound repair. Overall, this sustainable, bioactive hydrogel represents a promising alternative for advanced wound care. Full article

Chronic wounds, diabetic foot ulcers, venous leg ulcers, and pressure injuries affect millions of patients worldwide and cost healthcare systems in the order of $150 billion annually, yet treatment options have changed less than the scale of the problem would suggest. Biofilm formation, documented in up to 78% of chronic wounds, is a central cause: bacteria embedded in extracellular polymeric matrices tolerate antimicrobial concentrations up to 1000-fold higher than planktonic cells and sustain a chronic inflammatory state that actively prevents tissue repair. Hydrogels, crosslinked polymer networks with high water content and tunable physicochemical properties, have been widely studied as platforms for addressing these challenges, though the distance between laboratory results and clinical practice remains considerable. While recent reviews have summarized hydrogel materials or antimicrobial strategies in isolation, this review takes a different approach: we treat infection, biofilm persistence, and impaired regeneration as interconnected processes that must be addressed simultaneously, and we examine biofilm management as a distinct therapeutic target rather than merely a subset of antimicrobial delivery. We analyze hydrogel-based wound care across three integrated domains: design principles (natural, synthetic, and hybrid polymer systems; crosslinking strategies; and stimuli-responsive architectures), antimicrobial delivery (silver, antibiotics, antimicrobial peptides, natural agents, and controlled-release systems), and biofilm management (nanoparticle-mediated disruption, enzymatic EPS degradation, photodynamic approaches, quorum-sensing inhibition, and anti-adhesive surface engineering). For each area, we critically evaluate what the preclinical evidence supports, where it falls short, and what would be needed to bridge the gap to clinical application. Translation remains uneven. Among the many FDA- and EMA-cleared hydrogel dressings currently in clinical use, most are simple moisture-retaining or silver-containing formulations, while the multifunctional systems that dominate the research literature are at earlier stages of development. We discuss the main translational priorities, including more predictive preclinical models, long-term nanomaterial safety, harmonized outcome reporting, manufacturing scalability, and health economic evidence, as areas where further work can meaningfully accelerate clinical adoption. Full article

Introduction: Type 2 diabetes mellitus predisposes patients to neuropathy, peripheral arterial disease, and diabetic foot ulcers, which may become infected and progress to osteomyelitis, increasing the risk of amputation. The growing prevalence of multidrug-resistant organisms complicates management. Photodynamic therapy (PDT), which combines a photosensitizer with light-emitting diode irradiation to generate reactive oxygen species, has emerged as a potential adjunctive antimicrobial strategy without inducing resistance. Objective: To describe clinical outcomes observed in patients with diabetic foot osteomyelitis treated with adjunctive photodynamic therapy (PDT), with emphasis on wound evolution, limb preservation, and healing time. Methods: This prospective case series included patients with osteomyelitis secondary to infected diabetic foot ulcers treated at a university hospital. Demographic and clinical data were collected from medical records. Serial photographic documentation was used to monitor wound progression and tissue response during therapy. Results: Sixteen patients with diabetic foot osteomyelitis were included. Complete healing was achieved in 13 patients (81.25%), while 2 patients (12.5%) remained under treatment with partial healing and 1 (6.25%) underwent major amputation. Among healed patients, healing time ranged from 19 to 546 days, with a median of 118 days. The number of photodynamic therapy sessions ranged from 2 to 12, depending on the clinical course of each case. Healing time varied among patients, and the hallux was the most frequent site of osteomyelitis. During follow-up, only one patient underwent major amputation, whereas the remaining patients either achieved complete healing or were still under treatment at the time of analysis. Healing time was comparable between insulin-dependent and non-insulin-dependent diabetes, although numerically shorter in the latter. Longer healing periods were associated with more treatment sessions. Conclusions: In this prospective uncontrolled case series, adjunctive PDT was associated with favorable clinical evolution in a subset of patients with diabetic foot osteomyelitis. However, because of the small sample size and the absence of a control group, these findings should be considered preliminary and hypothesis-generating. Full article

Background/Objectives: Understanding the available interventions and circumstances under which physical therapy is administered to patients with diabetic foot ulcers is important to provide more evidence regarding physical therapy and associated outcomes in this population. This study aimed to investigate the scope, nature, and extent of literature on physical therapy interventions for adults with diabetic foot ulcers. Methods: Articles on physiotherapy interventions for adults with diabetic foot ulcers published up to 30 June 2024 were included. Relevant articles were identified through searches of PubMed, Scopus, MEDLINE, and the Cochrane Library databases. Opinion articles, study protocols, meeting abstracts, and articles that did not describe physical therapy interventions were excluded. Results: The systematic search identified 13 articles that met the inclusion criteria. Eleven of the 13 articles were specifically related to outpatient physical therapy. Outpatient physiotherapy included unloading gait instruction, ankle stretching instruction, progressive resistance training, and aerobic exercise. In two other cases, exercise instructions were practiced in the early postoperative period of the wound during the hospitalization period. A multidisciplinary approach aimed at improving postoperative activities of daily living was included. The main efficacy indices were the wound reduction rate, plantar pressure reduction, hemodynamics, ankle joint range of motion, walking ability, and other physical function-related parameters. Conclusions: Physiotherapy during outpatient follow-up may contribute to preventing wound deterioration and maintaining physical function in patients with stable DFUs. However, standardized protocols regarding intervention timing, exercise intensity, and wound severity remain unestablished, and interventions should be applied cautiously based on individual clinical conditions. Full article

Diabetic chronic wounds (particularly diabetic foot ulcers) are difficult to heal due to factors such as high glucose levels, infection, and inflammatory imbalance. In severe cases, they can lead to tissue necrosis and amputation. Hydrogel materials, as moist wound dressings, possess high water content, biocompatibility, and tunability, making them an important platform for promoting diabetic wound healing. In recent years, novel smart hydrogels have been developed to integrate multiple functions. They respond to abnormal stimuli in the wound microenvironment—such as acidic pH, high glucose levels, or excessive reactive oxygen species—to trigger the release of drugs, delivering on-demand antimicrobial, antioxidant, and anti-inflammatory effects. Simultaneously, they modulate immune responses (promoting macrophage polarization toward the M2 type) and stimulate angiogenesis, creating a microenvironment conducive to tissue regeneration. Some hydrogels incorporate antimicrobial agents, anti-biofilm components, or photothermal/photodynamic agents to effectively eliminate drug-resistant pathogens and control infections. Others serve as carriers for delivering stem cells and their exosomes, enhancing cell survival rates and releasing growth factors to accelerate wound healing. This review systematically summarizes recent advances in hydrogel strategies for diabetic wound treatment, focusing on stimulus-responsive hydrogels, antimicrobial and immune modulation mechanisms, pro-angiogenic and oxygen-supplying therapies, smart dressings and monitoring technologies, integration of stem cells and exosomes, as well as hydrogel injection, self-healing, and adhesion properties. Based on this, we analyze challenges and prospects for clinical translation of these strategies. Collectively, functionalized hydrogels hold promise as multifunctional therapeutic platforms for diabetic non-healing wounds. They offer a multi-pronged approach to disrupt the vicious cycle of “infection–inflammation–tissue destruction” thereby achieving more efficient wound healing. Full article