Search Results (409)

Diabetic wounds are characterized by a refractory healing cycle resulting from the synergistic effects of hyperglycemic microenvironment, oxidative stress, bacterial infection, and impaired angiogenesis. Conventional hydrogel dressings, with limited functionality, struggle to address the complexities of chronic diabetic ulcers. Smart hydrogels, possessing biocompatibility, porous architectures mimicking extracellular matrix, and environmental responsiveness, have emerged as promising biomaterials for diabetic wound management. This review systematically elucidates the specific response mechanisms of smart hydrogels to wound microenvironmental stimuli, including pH, matrix metalloproteinase-9 (MMP-9), reactive oxygen species (ROS), and glucose levels, enabling on-demand release of antimicrobial agents and growth factors through dynamic bond modulation or structural transformations. Subsequently, the review highlights recent advances in novel hydrogel-based sensors fabricated via optical (photonic crystal, fluorescence) and electrochemical principles for real-time monitoring of glucose levels and wound pH. Finally, critical challenges in material development and scalable manufacturing of multifunctional hydrogel components are discussed, alongside prospects for precision diagnostics and therapeutics in diabetic wound care. Full article

Background: Chronic wounds are a growing clinical challenge due to their prolonged healing time and associated healthcare burden. Combined therapeutic approaches, including topical oxygen therapy (TOT) and negative-pressure wound therapy (NPWT), have shown promise in enhancing wound healing. This pilot exploratory study aimed to assess the clinical effectiveness of combined TOT and NPWT in chronic wound treatment and to explore the prognostic value of selected laboratory and thermographic markers. Methods: Eighteen patients with chronic wounds due to type 2 diabetes mellitus or chronic venous insufficiency were treated with either TOT alone (control group) or TOT combined with NPWT (intervention group). Wound characteristics, thermographic data, and laboratory parameters (NLR, MLR, PLR, CRP, and total protein) were collected at baseline and during therapy. The primary endpoints were the total treatment duration and complete wound closure. Statistical analyses were exploratory and used non-parametric tests, correlation analyses, and simple linear regression. Results: Ulcer duration was significantly associated with the wound surface area. Lower serum total protein levels correlated negatively with ulcer duration, wound size, and granulation tissue area. A significant reduction in treatment duration was observed in the intervention group compared to the controls. One strong correlation was found between MLR and peripheral wound temperature on day 7 in the control group. No significant group differences were observed in wound size or thermographic measures after one week of treatment. Conclusions: Combining TOT and NPWT may reduce treatment duration in chronic wound management. Selected laboratory and thermographic markers show promise as prognostic tools. These exploratory findings require confirmation in larger, randomized trials. Full article

Honey is a natural product of honeybees that has been consumed for centuries due to its nutritional value and potential health benefits. Recent scientific research has focused on its antioxidant capacity, which is linked to a variety of bioactive compounds such as phenolic acids, enzymes (e.g., glucose oxidase, catalase), flavonoids, ascorbic acid, carotenoids, amino acids, and proteins. Together, these components work synergistically to neutralize free radicals, regulate antioxidant enzyme activity, and reduce oxidative stress. This review decisively outlines the antioxidant effects of honey and presents compelling clinical and experimental evidence supporting its critical role in preventing diseases associated with oxidative stress. Honey stands out for its extensive health benefits, which include robust protection against cardiovascular issues, notable anticancer and anti-inflammatory effects, enhanced glycemic control in diabetes, immune modulation, neuroprotection, and effective wound healing. As a recognized functional food and dietary supplement, honey is essential for the prevention and adjunct treatment of chronic diseases. However, it faces challenges due to variations in composition linked to climatic conditions, geographical and floral sources, as well as hive management practices. The limited number of large-scale clinical trials further underscores the need for more research. Future studies must focus on elucidating honey’s antioxidant mechanisms, standardizing its bioactive compounds, and examining its synergistic effects with other natural antioxidants to fully harness its potential. Full article

Background: Chronic wounds represent a persistent clinical challenge and impose a considerable burden on healthcare systems. These lesions often require multidisciplinary management due to underlying factors such as microbial colonization, impaired immunity, and vascular insufficiencies. Regenerative therapies, particularly autologous approaches, have emerged as promising strategies to enhance wound healing. Adipose tissue-derived stem cells (ADSCs) and platelet-rich plasma (PRP) may improve outcomes through paracrine effects and growth factor release. Methods: A prospective observational study was conducted on 31 patients with chronic wounds that were unresponsive to conservative treatment for over six weeks. Clinical and photographic evaluations were employed to monitor healing. All patients underwent surgical debridement, with adjunctive interventions—negative pressure wound therapy, grafting, or flaps—applied as needed. PRP infiltration and/or autologous adipose tissue transfer were administered based on wound characteristics. Wound area reduction was the primary outcome measure. Results: The cohort included 17 males and 14 females (mean age: 59 years). Etiologies included venous insufficiency (39%), diabetes mellitus (25%), arterial insufficiency (16%), and trauma (16%). Most lesions (84%) were located on the lower limbs. All patients received PRP therapy; five underwent combined PRP and fat grafting. Over the study period, 64% of the patients exhibited >80% wound area reduction, with complete healing in 48.3% and a mean healing time of 49 days. Conclusions: PRP therapy proved to be a safe, effective, and adaptable treatment, promoting substantial healing in chronic wounds. Autologous adipose tissue transfer did not confer additional benefit. PRP may warrant inclusion in national treatment protocols. Full article

Diabetic wounds are a devastating complication that cause chronic pain, recurrent infections, and limb amputations due to impaired healing. Despite advances in wound care, existing therapies often fail to address the underlying molecular dysregulation, highlighting the need for innovative and safe therapeutic approaches. Among these, D-amino acids such as D-tryptophan (D-Trp) have emerged as key regulators of cellular processes; however, their therapeutic potential in diabetic wounds remains largely unexplored. Here, we investigate the therapeutic potential of D-Trp in streptozotocin (STZ)-induced diabetic mice, comparing it with phosphate-buffered saline (PBS) controls and vascular endothelial growth factor (VEGF) as a positive control. Wound healing, inflammation, and histopathology were assessed. Protein and gene expression were analyzed via Western blot and RT-qPCR, respectively. Biolayer interferometry (BLI) measured the binding of D-Trp to hypoxia-inducible factor-1α (HIF-1α). D-Trp accelerated wound healing by modulating extracellular matrix (ECM) remodeling, signaling, and apoptosis. It upregulated matrix metalloproteinases (MMP1, MMP3, MMP-9), Janus kinase 2 (JAK2), and mitogen-activated protein kinase (MAPK) proteins while reducing pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], IL-6). D-Trp also suppressed caspase-3 and enhanced angiogenesis through HIF-1α activation. These findings suggest that D-Trp promotes healing by boosting ECM turnover, reducing inflammation, and activating MAPK/JAK pathways. Thus, D-Trp is a promising therapeutic for diabetic wounds. Full article

Background: Wound healing in diabetic individuals is a prolonged process, often complicated by infections and impaired tissue regeneration. Innovative strategies combining natural bioactive compounds are needed to enhance repair. Methods: This study reports the development and characterization of natural latex-based biomembranes (NLBs) incorporated with liposome-encapsulated curcumin and papain. The therapeutic efficacy of these composite dressings, in combination with red light-emitting diode (LED) phototherapy, was evaluated in a diabetic rat model. NLBs were produced by blending natural latex with multilamellar liposomes containing either curcumin, papain, or both. In vivo wound healing was assessed by applying the biomembranes to the dorsal lesions and administering red LED irradiation (650 ± 20 nm, 10 min every 48 h) over 11 days. Results: Fourier transform infrared spectroscopy (FTIR) confirmed that the integration of liposomes did not induce significant chemical alterations to the latex matrix. The treated diabetic rats exhibited enhanced wound contraction, with the curcumin and papain groups demonstrating up to 99% and 95% healing, respectively. Plasma fructosamine levels were significantly reduced (p < 0.05), indicating improved glycemic control. Conclusions: Combining NLBs with bioactive-loaded liposomes and phototherapy accelerated wound healing in diabetic rats. This multifunctional platform shows promise for the treatment of chronic wounds in diabetic patients. Full article

Diabetic foot ulcers (DFUs), which affect approximately 15% of individuals with diabetes mellitus (DM), result from complex molecular disturbances involving chronic hyperglycemia, immune dysfunction, and infection. At the molecular level, chronic hyperglycemia promotes the formation of advanced glycation end products (AGEs), activates the AGE-RAGE-NF-κB axis, increases oxidative stress, and impairs macrophage polarization from the pro-inflammatory M1 to the reparative M2 phenotype, collectively disrupting normal wound healing processes. The local wound environment is further worsened by antibiotic-resistant polymicrobial infections, which sustain inflammatory signaling and promote extracellular matrix degradation. The rising threat of antimicrobial resistance complicates infection management even further. Recent studies emphasize that optimal glycemic control using antihyperglycemic agents such as metformin, Glucagon-like Peptide 1 receptor agonists (GLP-1 receptor agonists), and Dipeptidyl Peptidase 4 enzyme inhibitors (DPP-4 inhibitors) improves overall metabolic balance. These agents also influence angiogenesis, inflammation, and tissue regeneration through pathways including AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and vascular endothelial growth factor (VEGF) signaling. Evidence indicates that maintaining glycemic stability through continuous glucose monitoring (CGM) and adherence to antihyperglycemic treatment enhances antibiotic effectiveness by improving immune cell function and reducing bacterial virulence. This review consolidates current molecular evidence on the combined effects of glycemic and antibiotic therapies in DFUs. It advocates for an integrated approach that addresses both metabolic and microbial factors to restore wound homeostasis and minimize the risk of severe outcomes such as amputation. Full article

Chronic, non-resolving inflammation is a major contributor to impaired wound healing in diabetes. Annexin A1 (AnxA1), a pro-resolving mediator, and its mimetic peptide Ac_2–26 have demonstrated therapeutic potential in modulating inflammatory responses. In this study, we evaluated the effects of topical Ac_2–26 hydrogel in a streptozotocin-induced diabetic wound model. Treatment significantly accelerated wound closure, improved tissue architecture, and reduced leukocyte infiltration. Immunohistochemical analysis revealed diminished mast cell accumulation and IL-1β expression in treated wounds. Complementary transcriptomic profiling supported the downregulation of pro-inflammatory genes, including Il1b and mast cell-related mediators, confirming the peptide’s regulatory effect on the wound immune landscape. Mounting evidence suggests that dysregulated mast cell activity plays a role in the heightened inflammatory tone and delayed tissue repair observed in diabetic wounds. In our model, Ac_2–26 hydrogel treatment attenuated IL-1β expression, suggesting an indirect downregulation of NLRP3 inflammasome activation, potentially mediated through mast cell modulation, though effects on other cell types within the wound microenvironment cannot be excluded. While definitive causality cannot be assigned, the integration of histological and transcriptomic data highlights mast cells as contributors to the IL-1β-driven inflammatory burden in diabetic wounds. These findings underscore the immunomodulatory capacity of Ac_2–26 and its potential to restore resolution pathways in chronic wound settings, positioning it as a promising candidate for future therapeutic development. Full article

The effective healing of chronic wounds requires balancing antimicrobial activity with tissue regeneration. In this study, we developed a novel, eco-friendly synthesis method using Artemisia argyi extract to produce silver nanoparticles (AgNPs), addressing toxicity concerns associated with conventional chemical synthesis methods. Through optimization of multiple synthesis parameters, monodisperse spherical AgNPs with an average diameter of 6.76 ± 0.27 nm were successfully obtained. Plant-derived compounds from Artemisia argyi extract acted as efficient mediators for both reduction and stabilization, yielding nanoparticles with high crystallinity. The synthesized AgNPs exhibited potent antibacterial activity against both Gram-negative and Gram-positive bacteria, with minimum inhibitory concentrations of 8 μg/mL against Escherichia coli and 32 μg/mL against Staphylococcus aureus, while maintaining high biocompatibility with L929 fibroblasts at concentrations ≤ 8 μg/mL. When integrated into polylactic acid/collagen type I (PLA/Col1) nanofibrous matrices, the optimized 0.03% AgNPs/PLA/Col1 dressing significantly accelerated wound healing in a diabetic rat model, achieving 94.62 ± 2.64% wound closure by day 14 compared to 65.81 ± 1.80% observed in untreated controls. Histological analyses revealed a dual-functional mechanism wherein controlled silver ion release provided sustained antibacterial protection, while concurrently promoting tissue regeneration characterized by enhanced collagen deposition, reduced inflammation, and increased neovascularization. This innovative approach effectively addresses critical challenges in diabetic wound care by providing simultaneous antimicrobial and regenerative functions within a single biomaterial platform. Full article

Chronic diabetic wounds affect 15–20% of patients and are characterized by impaired healing due to disrupted hemostasis, inflammation, proliferation, and extracellular matrix (ECM) remodeling. Low-level light therapy (LLLT) has emerged as a promising noninvasive strategy for enhancing tissue regeneration. Here, we developed a multispectral pulsed LED system combining red and near-infrared light to stimulate wound healing. In vitro photostimulation of human keratinocytes and fibroblasts on biomimetic hydrogels enhanced adhesion, spreading, migration, and proliferation via increased focal adhesion kinase (pFAK), paxillin, and F-actin expression. In vivo, daily LED treatment of streptozotocin-induced diabetic wounds accelerated closure and improved ECM remodeling. Histological and molecular analyses revealed elevated levels of MMPs, interleukins, collagen, fibronectin, FGF2, and TGF-β1, supporting regenerative healing without excessive fibrosis. These findings demonstrate that multispectral pulsed photobiomodulation enhances diabetic wound healing through focal adhesion-mediated cell migration and ECM remodeling, offering a cost-effective and clinically translatable approach for chronic wound therapy. Full article

Hydrogels possess advantages for providing a moist wound environment and enabling drug or cell delivery. Wound healing is a complex, multistage process where macrophages play a pivotal role; they influence inflammation resolution, anti-inflammatory cytokine production, angiogenesis, and extracellular matrix remodeling. Combining hydrogel materials with adoptive M2 macrophages offers a promising adoptive cell therapy approach to accelerate healing. In the present study, sodium alginate, a natural polymer, was harnessed to create hydrogel sponges embedded with M2 macrophages for application to chronic wounds. Hydrogel sponges were capable of preserving the characteristics of M2 macrophages, secreting functional cellular factors, and maintaining viability. Hydrogel sponges loaded with M2 type macrophages could promote chronic wound healing in the back of type 2 diabetic mice. In vitro and in vivo experiments demonstrated that M2 macrophages successfully grew and proliferated within the hydrogel sponges, exhibiting anti-inflammatory effects, which is expected to offer a cell therapy approach to diabetic wound treatment. Full article

Chronic wounds, such as diabetic ulcers and pressure injuries, remain a major global health burden, affecting over 40 million people worldwide and imposing significant socioeconomic strain. Hydrogel-based wound dressings have gained clinical attention for their ability to maintain moisture, mimic the extracellular matrix, and support tissue regeneration. However, traditional hydrogels often lack the mechanical robustness, antimicrobial efficacy, and dynamic responsiveness needed to treat complex wound environments effectively. To address these limitations, nanohybrid hydrogels, composite systems that integrate functional nanomaterials into hydrogel matrices, have emerged as intelligent platforms for advanced wound care. These systems enable multifunctional therapeutic action, including antibacterial activity, antioxidant regulation, angiogenesis promotion, immune modulation, and stimuli-responsive drug delivery. This review synthesizes recent advances in nanohybrid hydrogel design, beginning with an overview of traditional polymeric systems and their constraints. We categorize functional mechanisms according to biological targets and classify nanohybrid architectures by material type, including metal-based nanoparticles, nanozymes, carbon-based nanomaterials, polymeric nanogels, and metal–organic frameworks. Representative studies are summarized in a comparative table, and challenges related to biosafety, clinical translation, and design optimization are discussed. Nanohybrid hydrogels represent a rapidly evolving frontier in wound care, offering bioresponsive, multifunctional platforms with the potential to transform chronic wound management. Full article

Neutrophils are essential components of innate immunity, executing a range of effector functions including phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETs). A key hallmark of NET formation is the presence of citrullinated histone H3 (CitH3), produced by peptidylarginine deiminases (PAD2 and PAD4) to facilitate chromatin decondensation. While NETs play critical antimicrobial roles, excessive or dysregulated NET formation, termed NETosis, can drive tissue injury, chronic inflammation, and organ dysfunction across a wide spectrum of diseases. Beyond its structural role within NETs, CitH3 acts as a damage-associated molecular pattern (DAMP), amplifying immune activation and pathological inflammation. Elevated CitH3 levels have been identified as biomarkers in sepsis, viral infections, ischemia–reperfusion injury, organ transplantation, diabetic wounds, autoimmune diseases, and cancer. Despite increasing recognition of CitH3’s pathogenic contributions, its therapeutic potential remains largely untapped. This review summarizes recent advances in understanding the role of CitH3 in NETosis and immune dysfunction, highlights emerging strategies targeting CitH3 therapeutically, and identifies critical knowledge gaps. Collectively, these insights position CitH3 as a promising druggable biomarker for the diagnosis, prognosis, and treatment of acute and chronic inflammatory diseases. Full article

Chronic wounds, including diabetic foot ulcers and pressure sores, are becoming more prevalent due to aging populations and increased metabolic problems. These wounds often persist due to impaired healing, chronic inflammation, oxidative stress, and infections caused by multidrug-resistant pathogens, making conventional treatments—including antibiotics and antiseptics—largely inadequate. This creates an urgent need for advanced, biologically responsive therapies that can both combat infection and promote tissue regeneration. Probiotics have surfaced as a viable option owing to their capacity to regulate immune responses, impede pathogenic biofilms, and generate antibacterial and antioxidant metabolites. However, their clinical application is limited by poor viability, sensitivity to environmental conditions, and short retention at wound sites. Nanotechnology-based delivery systems address these limitations by protecting probiotics from degradation, enhancing site-specific delivery, and enabling controlled, stimuli-responsive release. Encapsulation techniques using materials like chitosan, PLGA, liposomes, nanogels, nanofibers, and microneedles have shown significant success in improving wound healing outcomes in preclinical and clinical models. This review summarizes the current landscape of chronic wound challenges and presents recent advances in probiotic-loaded nanotechnologies. It explores various nano-delivery systems, their mechanisms of action, biological effects, and therapeutic outcomes, highlighting the synergy between probiotics and nanocarriers as a novel, multifaceted strategy for managing chronic wounds. Full article