Search Results (673)

Background: Platelet-rich plasma (PRP) plays a crucial role in chronic wound healing by releasing growth factors that regulate inflammation, promote angiogenesis, and stimulate tissue regeneration. Methods and Results: Here, an animal source of PRP, named ApiRegenin and derived from cultivated deer blood, was established. Specific protein and non-protein biomarkers—including nicotinamide, palmitic acid, IGF, and fibronectin—were validated to ensure batch-to-batch quality control. The pharmacological properties of ApiRegenin in cultured cells transfected with DNA encoding HRE and NF-κB reporter constructs were validated, serving as a functional control. In a skin-defective model of db/db diabetic mice, accelerated wound healing was observed following ApiRegenin treatment. Histological analysis revealed enhancements of re-epithelialization, granulation tissue formation, and collagen deposition. In parallel, the immunofluorescence staining of CD31, α-SMA, and VEGF was upregulated, indicating the promotion of angiogenesis. Furthermore, ApiRegenin treatment shifted the local immune microenvironment toward an M2-like macrophage phenotype, characterized by the downregulation of iNOS and the contrastive upregulation of Arg-1. At the molecular level, transcriptomic enrichment analysis suggested the prominent involvement of the HIF-1, PI3K-Akt, and TNF signaling pathways. Conclusions: These findings demonstrate that ApiRegenin effectively accelerates diabetic wound healing by promoting angiogenesis and modulating macrophage polarization. Full article

Introduction: Diabetic foot ulcers (DFUs) are a debilitating complication of diabetes, and management by multidisciplinary foot teams have been shown to reduce serious sequelae, such as amputations. There are stark racial and ethnic disparities in morbidity and mortality from DFUs, and multidisciplinary care has been shown to reduce lower extremity amputations, length of hospital stays and readmissions. This is a review of the impact of multidisciplinary care on DFUs, particularly regarding social determinants of health, with an illustrative case. Case Presentation: This is a case of a 32-year-old African American male with Type 1 Diabetes, a history of poor glycemic control, attention deficit hyperactivity disorder, tobacco and marijuana use disorder, and multiple social and structural barriers to care. He presented with bilateral Wagner grade 3 DFUs with osteomyelitis to the emergency department, requiring hospitalization. Upon discharge, he was referred to a multidisciplinary diabetes clinic and received coordinated support from endocrinology, podiatry, vascular surgery, infectious disease, pedorthics, and behavioral health. Comprehensive evaluation, intensive wound care with adjuvant hyperbaric oxygen therapy, offloading, blood glucose management and medical source control of infection were established for his treatment plan. At the three-month follow-up, the patient’s wound beds had significantly improved, and his Hemoglobin A1c declined from 12.6% to 9.3%. The right plantar wound completely epithelialized, and the left foot wound showed 90% contracture. Review and Discussion: This case highlights the importance of integrated, multidisciplinary care for DFUs, particularly in addressing both the clinical and social drivers of complications from diabetes. Full article

Chronic, non-healing foot ulcers are the most common complication of diabetes and are associated with high morbidity, mortality, and substantial health-care costs. Impaired wound healing in diabetes results from a complex pathophysiology involving persistent inflammation, interrupted re-epithelialization, impaired neovascularization, and defective granulation tissue formation. Reconstituted high-density lipoprotein (rHDL), with its antioxidant and anti-inflammatory properties, may counteract these processes and thereby promote wound repair. We investigated the effect of topical administration of rHDL in full thickness excisional wounds in murine and porcine diabetic models. rHDL significantly enhanced wound closure in diabetic mice in a dose-dependent manner as compared to phosphate-buffered saline (PBS) control. Histological and immunohisto-chemical analysis showed that rHDL-treated wounds had increased collagen deposition, a higher number of alpha-smooth muscle actin-positive cells, greater macrophage infiltration, and decreased neutrophil infiltration compared to PBS controls. In contrast, in the porcine model no wound healing improvement was observed after daily topical application of rHDL. Administration of rHDL enhances wound closure in a murine model of diabetic wound healing by promoting collagen production and modulating inflammation. However, lack of efficacy in a more physiologically relevant pre-clinical porcine model under the experimental conditions tested does not support further development of a topical rHDL formulation for diabetic wound healing indications. Full article

Chronic diabetic foot ulcers remain a major clinical challenge due to persistent inflammation, impaired tissue repair, and microbial dysbiosis. We report the case of a 62-year-old male with diabetes mellitus presenting with two chronic diabetic foot ulcers managed using different local treatment strategies within the same patient. One wound received conventional wound care, while the second was treated with topical probiotic therapy containing Enterococcus faecium and Saccharomyces boulardii. Wound progression was assessed over eight weeks using the RESVECH 2.0 scale (Results Expected from Chronic Wound Healing), serial wound measurements, and microbiological cultures obtained before and after treatment. Although baseline wound characteristics differed between lesions—with the probiotic-treated ulcer being smaller and less severe at presentation—the probiotic-treated plantar ulcer demonstrated progressive reduction in RESVECH 2.0 scores and complete closure by week 8, whereas the conventionally treated ulcer remained partially open at the end of follow-up. Serial microbiological assessment demonstrated persistent colonization with Providencia stuartii and changes in antimicrobial susceptibility profiles during follow-up. Although limited to a single-patient observation, these findings support further investigation of microbiome-targeted approaches as adjunctive strategies in chronic wound management. Full article

Osteoarthritis (OA) is a disabling joint disease characterised by cartilage degradation, synovial inflammation, and subchondral bone remodelling. Furthermore, catabolic inflammatory processes as well as dysregulated cellular signalling and oxidative stress are central to OA pathogenesis. Despite its growing global burden, currently available therapies primarily provide symptomatic relief and fail to target underlying molecular mechanisms and halt disease progression. Cold atmospheric plasma (CAP), a partially ionised, non-thermal gas that generates controlled reactive oxygen and nitrogen species (RONS), has emerged as a promising therapeutic modality capable of modulating redox-sensitive signalling pathways. CAP has demonstrated the capacity to suppress pro-inflammatory cytokine expression, enhance antioxidant defence mechanisms, influence macrophage polarisation, and stimulate tissue repair processes in rheumatoid arthritis, diabetic and dermal wound healing models. However, its potential as a disease-modifying therapy for the treatment of OA is not yet fully understood and warrants further experimental investigation. This review explores current pre-clinical evidence from different disease models, which may have implications for the potential application of CAP as a therapeutic intervention for OA, either as a disease-modifying therapy or as an adjuvant therapy for intra-articular drug delivery. Furthermore, key translational challenges including plasma parameter standardisation, interactions with synovial fluid and optimisation of joint-specific delivery strategies are discussed, identifying gaps that require further experimental investigation. Collectively, the findings of this review highlight CAP as a promising multimodal therapy with translational potential for the treatment of OA warranting further experimental validation and may open innovative avenues for future research. Full article

Background: Diabetes mellitus (DM) is a metabolic disease with an increasing global prevalence. It is characterized by chronic and systemic complications. Due to these complications, DM significantly impacts patients’ health-related quality of life (HRQoL). One of the most critical complications of DM is diabetic foot ulcers (DFUs), which have serious consequences for patients and healthcare systems. Objective: This study aimed to investigate variables potentially associated with HRQoL in patients with DFUs presenting to our wound care unit. Methods: This prospective cross-sectional study was conducted from February to May of 2023 at the Wound Care Unit of the General Surgery Department at Eskişehir City Hospital. A total of 209 patients who agreed to participate were included in the study. Data were collected via a structured questionnaire developed based on the literature, which included the Diabetic Foot Ulcer Scale–Short Form (DFS-SF). We used the Kolmogorov–Smirnov test, univariate analyses (Mann–Whitney U and Kruskal–Wallis tests), and multiple linear regression. Results: In the multivariate analysis, receipt of foot care education (p < 0.001), frequency of hospital applications due to DFU (p = 0.008), and Wagner classification (p = 0.012) were found to be predictors of HRQoL for DFUs (Adjusted R² = 0.206, F = 4.365, p < 0.001). Conclusions: To maintain a high HRQoL among DFU patients, they should immediately apply to specialized Wound Care Units, receive education, especially regarding early diagnosis and treatment, and receive multidisciplinary management for DFU. Full article

Diabetic wounds are a common complication of diabetes mellitus (DM), with healing often impaired by ferroptosis and persistent inflammation. This study investigated the effects of Ginkgo biloba flower extract (GBF) on diabetic wound healing by focusing on inflammation and ferroptosis. Chemical composition analysis identified 123 compounds in GBF containing 73 active ingredients of flavonoids and 12 terpenoids. In vivo, GBF treatment significantly accelerated the wound healing process in diabetic rats, and GBF promoted epithelial regeneration and collagen deposition by increasing the expression of CD31 and VEGF. It also enhanced the formation of new blood vessels. Mechanistically, GBF could inhibit the inflammatory response by reducing the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and inhibit the oxidative stress-induced ferroptosis by increasing the levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4). Proteomics analysis further confirmed its regulatory effects on inflammation and iron metabolism pathways. In vitro, GBF promoted the survival and migration of rat skin fibroblasts (RS1) while reducing the levels of reactive oxygen species (ROS) and Fe²⁺ in erastin-induced ferroptosis cells. In conclusion, GBF promotes diabetic wound healing by inhibiting ferroptosis and inflammation. Full article

Diabetic foot ulcers (DFUs) are among the most severe complications affecting diabetic patients, and dressing therapy is one of the standard treatments for DFUs. However, traditional dressings are inadequate for addressing the complex microenvironment of DFUs. Consequently, advanced natural polymer-based dressings have attracted extensive research attention in diabetic foot care due to their biocompatibility, low immunogenicity, and biodegradability. These natural polymer materials include collagen, gelatin, chitosan (CS), hyaluronic acid (HA), alginate, and cellulose. This review systematically analyzes the pathophysiological mechanisms underlying the difficult healing of DFUs and the advantages of natural polymer-based dressings in diabetic wound healing, highlights preclinical studies, and synthesizes evidence from clinical research. Moreover, we pinpoint the challenges associated with these dressings and propose future directions for the improvement of diabetic wound care. Full article

Background/Objectives: Foot and ankle presentations during Hajj occur in a dense mass-gathering environment where prolonged walking, heat exposure, crowding, variable footwear, and limited self-care can interact with chronic disease and wound vulnerability. Previous Hajj studies have described foot injuries and diabetes-related complications, but less is known about whether simple high-risk foot documentation flags identify presentation records with higher care-pathway intensity. The primary objective was to estimate the presentation-level burden of core high-risk foot profiles among pilgrims presenting with foot and ankle conditions during Hajj 2025. Secondary objectives were to evaluate associations with a surgery-coded care-intensity indicator, hospital referral, and component heterogeneity. Methods: This observational presentation-level analysis included 3957 foot and ankle presentation records. The unit of analysis was the presentation/case record, not a unique individual pilgrim. A core high-risk foot profile was defined as diabetes, neuropathy, diabetic foot ulcer, foot ulcer, complications of open wound, or osteomyelitis. The primary outcome was a surgery-coded care-intensity indicator, defined solely from treatment documentation containing “Surgery” and interpreted as a care-pathway proxy rather than confirmed operating-room surgery. Logistic regression estimated crude and adjusted odds ratios (ORs); exploratory risk-category analyses assessed heterogeneity within the composite profile. Results: Core high-risk foot profiles were identified in 1793/3957 presentations (45.3%). The primary outcome occurred in 239/1793 high-risk presentations (13.3%) and 201/2164 non-high-risk presentations (9.3%), an absolute difference of 4.0 percentage points. The crude OR was 1.50 (95% CI 1.23–1.83; p < 0.001). The association persisted in the primary adjusted model (adjusted OR 1.47; 95% CI 1.20–1.79; p < 0.001) and in the extended clinical sensitivity model (adjusted OR 1.47; 95% CI 1.20–1.80; p < 0.001). Care pathways and secondary outcomes are summarized was also more frequent in high-risk presentations (12.2% vs. 9.8%; crude OR 1.28; 95% CI 1.05–1.57; p = 0.017). Exploratory category analysis showed that chronic-risk-only presentations had a primary outcome rate similar to non-high-risk presentations (9.0% vs. 9.3%), whereas ulcer/wound/deep-infection presentations had a higher rate (17.3%; crude OR 2.04; 95% CI 1.63–2.55; p < 0.001). Model discrimination was modest (C-statistics 0.55–0.64). Conclusions: Core high-risk foot flags were common among Hajj foot and ankle presentation records and were associated with surgery-coded care-intensity and referral documentation. However, the composite was clinically heterogeneous, the outcome was not a validated surgery endpoint, and the models were not prediction tools. These findings support cautious use of high-risk foot flags as operational prompts for assessment and pathway planning rather than as standalone clinical risk estimates. Full article

Background/Objectives: Chronic diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) remain a major source of morbidity, healthcare utilization, and limb loss, despite adherence to established standards of care protocols and the widespread availability of advanced wound technologies. Many advanced modalities only target isolated aspects of wound healing and fail to address the complex, interdependent pathophysiology of chronic wounds, particularly tissue hypoxia, edema, impaired microcirculation, and persistent inflammation. Cyclical Pressurized Topical Wound Oxygen (TWO₂) therapy is a home-based, multimodal intervention that combines humidified topical oxygen delivery with cyclical non-contact compression to address these core drivers simultaneously. Methods: This review synthesizes mechanistic rationale and evidence from randomized controlled trials, long-term venous ulcer studies, and real-world comparative effectiveness analyses. Emphasis is placed on the large cohort study by Yellin et al., which directly compared TWO₂ with other advanced modalities including negative pressure wound therapy (NPWT), skin substitutes, and growth factor therapies. Results: Across these studies, TWO₂ therapy is consistently associated with improved healing durability, reduced recurrence, and substantial reductions in hospitalization and amputation rates compared with both standard care and advanced wound therapies. Conclusions: The convergence of randomized and real-world evidence supports TWO₂ therapy as a clinically meaningful and mechanism-driven adjunctive treatment option for patients with chronic, high-risk lower-extremity wounds. Full article

Diabetic wounds are characterized by persistent hyperglycemia, excessive ROS accumulation, sustained inflammation, and impaired angiogenesis, yet current treatments remain suboptimal. To address these challenges, we developed a mild heat stimulating and microenvironment reprogramming hydrogel (termed C-4-N) via a green synthetic strategy. L-Arginine (L-Arg) triggered the spontaneous self-polymerization of protocatechuic aldehyde (PA) into poly (protocatechuic aldehyde) (PPA) nanoparticles, onto which ginsenoside Compound K (CK) was subsequently loaded, yielding CK/L-Arg/PPA nanoparticles. These nanoparticles were then uniformly embedded into a dynamic disulfide network composed of α-lipoic acid (LA)-modified chitosan (CS-LA) and 4-arm-PEG-SH under UV irradiation without toxic photo-initiators, forming the C-4-N hydrogel. The C-4-N hydrogel reprogrammed the diabetic wound microenvironment through three synergistic mechanisms, lowering blood glucose and scavenging ROS via the coordinated actions of LA, CK and PPA, promoting M1-to-M2 macrophage polarization via downregulation of pro-inflammatory cytokines (TNF-α, IL-6) and upregulation of anti-inflammatory cytokines (IL-10, TGF-β1), further amplified by mild photothermal stimulation of 40–43 °C. In a diabetic rat model, the C-4-N hydrogel achieved a near-complete wound closure rate of 99.49 ± 0.10% on day 13 upon mild photothermal stimulation, accompanied by enhanced re-epithelialization, organized collagen deposition, vascular maturation, and systemic glucose regulation. In summary, this green synthesized, mild heat-stimulating hydrogel establishes a synergistic microenvironment reprogramming paradigm for chronic diabetic wound managements. Full article

Diabetic wounds remain a major clinical challenge due to impaired healing associated with persistent inflammation, oxidative stress, and microvascular dysfunction. Plasma-based therapies have emerged as promising approaches for promoting tissue repair; however, comparative evidence regarding different plasma modalities remains limited. In this study, we evaluated and compared the effects of atmospheric pressure cold plasma (APCP) and plasma-activated water (PAW) on wound healing in a streptozotocin-induced diabetic rat model. Forty Wistar albino rats were randomly assigned to five groups: isotonic wet dressing, hydrocolloid dressing, APCP treatment, PAW application, and a non-diabetic control group. Wound healing was assessed using macroscopic evaluation, histopathological analysis, and biochemical measurements of systemic oxidative status. PAW treatment significantly accelerated wound closure during the early healing phase compared with conventional dressing methods (p < 0.05). Histological findings demonstrated enhanced re-epithelialization, increased collagen deposition, and improved follicular regeneration in the PAW group. Although total oxidant status (TOS) did not differ significantly among groups (p = 0.996), total antioxidant status (TAS) was significantly increased following PAW treatment (p < 0.05), indicating a more favorable systemic antioxidant profile. These findings suggest an association between improved wound healing and a more favorable systemic antioxidant profile following PAW treatment. However, because local wound-level redox parameters and molecular markers were not assessed, the contribution of redox-related mechanisms remains to be clarified. Moreover, PAW demonstrated superior therapeutic efficacy compared with direct plasma application, highlighting its potential as a non-invasive approach for diabetic wound management. Full article

Background and Objectives: Diabetes mellitus (DM) is frequently associated with impaired wound healing due to persistent oxidative stress, chronic inflammation, and dysregulated proteasome activity, leading to delayed tissue repair and increased risk of chronic ulcers. The present study aimed to investigate the role of the immunoproteasome system in diabetic wound healing, with a particular focus on its involvement in oxidative stress and inflammatory pathways, and to evaluate whether pharmacological inhibition with ONX-0914 improves tissue repair. Materials and Methods: Experimental diabetes was induced in rats using streptozotocin (STZ), and the animals were allocated to three groups: healthy control, STZ-induced diabetic, and STZ + ONX-0914 treatment. Wound healing was evaluated by macroscopic analysis of wound closure and histopathological examination at days 3, 7, and 14. Oxidative stress and antioxidant status were assessed by measuring malondialdehyde (MDA) levels and antioxidant enzyme activities (SOD, CAT, and GSH-Px) in serum and wound tissues. Proteasome activity was analyzed fluorometrically, while systemic and local inflammatory responses were determined by ELISA and Western blot analysis of IL-1β, TNF-α, and IL-6. Results: STZ-induced diabetes significantly delayed wound closure, increased lipid peroxidation, reduced antioxidant enzyme activities, and elevated systemic and tissue inflammatory cytokine levels. Treatment with ONX-0914 markedly accelerated wound closure and improved histological healing parameters, including re-epithelialization, granulation tissue formation, and angiogenesis. Moreover, ONX-0914 significantly reduced MDA levels while restoring SOD, CAT, and GSH-Px activities in both serum and wound tissues. The treatment also inhibited proteasome activity and significantly suppressed the expression of IL-1β, TNF-α, and IL-6. Conclusions: ONX-0914 significantly improves diabetic wound healing by restoring antioxidant defenses, reducing oxidative damage, and attenuating inflammatory signaling pathways. These findings suggest that immunoproteasome inhibition represents a promising therapeutic strategy for enhancing tissue repair in diabetic conditions. Full article

Diabetic foot ulceration is a severe and common chronic complication of diabetes, accompanied by excessive reactive oxygen species (ROS) accumulation, persistent bacterial infection, prolonged inflammation, and insufficient angiogenesis. Traditional single-function wound dressings fail to simultaneously resolve these pathological barriers, leading to unsatisfactory healing outcomes. In this study, we developed a multifunctional composite hydrogel (E/MGel) by introducing mussel adhesive protein (MAP) into methacrylated hyaluronic acid (mHA) to construct an antibacterial and antioxidant delivery system, which was further loaded with epidermal growth factor (EGF) to promote angiogenesis. The as-prepared E/MGel exhibited a uniform porous structure, favorable rheology, high swelling ratio, and sustained protein release behavior. In vitro results demonstrated that E/MGel exerted potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E.coli), high ROS scavenging efficiency, good cytocompatibility, and remarkable pro-angiogenic effect on endothelial cells. In a mouse model of diabetic MRSA-infected full-thickness skin defect, E/MGel significantly accelerated wound closure, reduced bacterial burden, downregulated pro-inflammatory cytokines, promoted collagen deposition, and enhanced neovascularization. Meanwhile, no obvious systemic toxicity was observed. Taken together, this multifunctional hydrogel integrates antibacterial, antioxidant, and pro-angiogenic capacities to break the pathological vicious cycle of diabetic wounds, providing a promising and safe strategy for the clinical treatment of diabetic infected wounds. Full article

Background: Biofilms consist of complex microbial communities embedded in an extracellular matrix which confer resistance to the most used antimicrobial agents. Chronic wounds are often associated with burns, trauma, surgery, diabetes and peripheral vascular disease. They are characterized by a marked delay in wound healing favoring the development of microbial biofilms, which in turn further delay tissue regeneration. Staphylococcus aureus, Staphylococcus epidermidis, and methicillin-resistant staphylococci biofilms are found in chronic wounds, seriously hindering wound treatment. Vitreoscilla filiformis, a Gram-negative non-pathogenic filamentous bacterium, has been shown to improve atopic dermatitis by reducing S. aureus colonization and inducing antioxidant responses in the skin. Objectives: The aim of the present study was to evaluate the antimicrobial, anti-inflammatory, and regenerative activities of the V. filiformis supernatant (VFS). Methods: The effect of VFS on bacteria growth was assessed by microbial growth kinetics and biofilm formation and dispersal. Antioxidant potential was determined by DPPH-scavenging ability and reduction in intracellular reactive oxygen species (ROS). The regenerative properties were assessed by scratch assay. Results: V. filiformis VFS holds strong anti-biofilm activity against S. aureus, S. epidermidis and methicillin-resistant S. aureus (MRSA), acting during both biofilm formation and dispersion. The decrease in biofilm mass is accompanied by a significant increase in the planktonic form compared to the untreated cells. Moreover, VFS is characterized by an interesting antioxidant activity, as demonstrated by a cell-free DPPH assay and a neutrophil-based in vitro assay. In addition, VFS can stimulate tissue regeneration in human dermal fibroblasts and keratinocytes. Conclusions: The demonstration of anti-biofilm, antioxidant and regenerative properties of V. filiformis supernatant could be exploited for the treatment of biofilm-associated wound infections. Full article