Carbonized Polymer Dot-Tannic Acid Nanoglue: Tissue Reinforcement with Concurrent Fluorescent Tracking, Insulin Delivery, and Reactive Oxygen Species Regulation for Normal and Diabetic Wound Healing.

Sustained ROS scavenging and pericellular oxygenation by lignin composites rescue HIF-1α and VEGF levels to improve diabetic wound neovascularization and healing.

Diabetic wounds pose a persistent challenge due to their slow healing nature, primarily caused by bacterial infection and excessive reactive oxygen species (ROS)-induced inflammation. In this study, carbon dots with synergistic antibacterial and antioxidant properties, referred to as AA-CDs, are developed specifically for diabetic wound healing using a straightforward solvothermal method. By utilizing cost-effective precursors like citric acid and ascorbic acid, AA-CDs are engineered to possess tailored functions of photothermal sterilization and ROS scavenging. The resulting AA-CDs demonstrats broad-spectrum antibacterial activity, particularly against multidrug-resistant strains, along with efficient ROS scavenging both in solution and within cells. Additionally, AA-CDs exhibits a protective effect against oxidative stress-induced damage. Notably, with a high photothermal conversion efficiency (41.18%), AA-CDs displays heat-enhanced antioxidant performance, providing not only augmented ROS scavenging but also additional protection against oxidative stress, yielding a true "1 + 1 > 2" effect. To facilitate their use in vivo, AA-CDs are incorporated into a thermally responsive hydrogel, which exhibits evident anti-inflammatory properties by modulating inflammatory factors and significantly promots the healing of diabetic wounds. This study underscores the value of integrated platforms for diabetic wound healing and highlights the potential of versatile CDs as promising therapeutic agents in biomedical applications.

Angiogenesis and vasculogenesis: Inducing the growth of new blood vessels and wound healing by stimulation of bone marrow–derived progenitor cell mobilization and homing

A nanofibrous membrane loaded with doxycycline and printed with conductive hydrogel strips promotes diabetic wound healing in vivo

The accumulation of reactive oxygen species (ROS) in diabetic wounds leads to inflammation and impaired neovascularization. Recent studies have indicated that carbon dot nanozymes (C-dots) exhibiting superoxide dismutase (SOD)-like activity can neutralize excessive ROS and mitigate diseases associated with oxidative stress. Our study was designed to evaluate the therapeutic impact of C-dots on the healing of diabetic wounds and to unravel the complex molecular mechanisms through which these nanozymes modulate oxidative stress and inflammatory responses within the wound microenvironment. We synthesized C-dots from carbon fiber and confirmed their structure using transmission electron microscopy. The presence of carbon-carbon double bonds on the C-dots was verified with X-ray photoelectron spectroscopy. We assessed the scavenging capacity of C-dots for superoxide anion, hydroxyl radical, and nitric oxide radical using electron spin resonance spectroscopy. Their SOD-like activity and total antioxidant capacity were evaluated with commercial assay kits. In vitro experiments showed that C-dots effectively scavenged excessive ROS, protecting human keratinocytes, vascular endothelial cells, and fibroblasts from oxidative stress-induced damage. Concurrently, C-dots increased the migratory capacity of fibroblasts. In a streptozocin-induced diabetic mice model, C-dots application enhanced skin wound healing, evidenced by accelerated re-epithelialization and orderly collagen matrix assembly. Mechanistic investigations indicated that C-dots markedly suppressed ROS generation and diminished the levels of inflammatory cytokines in the wound environment. Additionally, C-dots induced an M2 polarization phenotype in macrophages and promoted neovascularization, indicating a transition from the inflammatory to the proliferative phase. Quantitative proteomic analysis was conducted to further clarify the underlying mechanisms of C-dots in ameliorating diabetic wounds. C-dots represent a robust nanomaterial-based strategy for treating diabetic wounds, with the ability to accelerate healing by alleviating oxidative stress, mitigating harmful inflammatory responses, and fostering angiogenesis. This highlights their significant therapeutic potential in the field of biomedicine.

The clinical treatment of chronic diabetic wounds is a long-standing thorny issue. Strategies targeting the diabetic micro-environment have been developed to promote wound healing. However, it remains challenging to reverse the adverse conditions and re-activate tissue regeneration and angiogenesis. In this work, we develop injectable hydrogels that are responsive to acidic conditions, reactive oxygen species (ROS), and high glucose levels in a diabetic wound micro-environment to sustainably deliver tannic acid (TA) to augment antibacterial, anti-inflammatory, and anti-oxidative activities. This triple-responsive mechanism is designed by introducing dynamic acylhydrazone and phenylboronic ester bonds to crosslink modified hyaluronic acid (HA) chains. At a diabetic wound, the acylhydrazone bonds may be hydrolyzed at low pH. Meanwhile, glucose may compete with TA, and ROS may oxidize the C-B bond to release TA. Thus, sustained release of TA is triggered by the diabetic micro-environment. The released TA effectively scavenges ROS and kills bacteria. In vivo experiments on diabetic mice demonstrate that the hydrogel dressing highly promotes angiogenesis and extracellular matrix (ECM) deposition, leading to eventual full healing of diabetic skin wounds. This micro-environment-triggered triple-responsive drug release provides a promising method for chronic diabetic wound healing.

Dual functional electrospun nanofiber membrane with ROS scavenging and revascularization ability for diabetic wound healing

Objective: Impaired wound healing in diabetic (DB) patients is a significant health problem; however, the roles that cytokines and innate immune cells contribute to this impaired healing are not completely understood. Approach: A mouse model was used to compare the innate immune response during DB and normal wound healing. Two 5-mm full-thickness wounds were created on the dorsal skin of BKS.Cg-m+/+Leprdb/J (DB) and C57BL/6 (wild-type) mice. Innate immune cell markers and cytokine mRNA levels were measured in wound biopsies during the first week of healing. Results: Innate immune cell influx (typified by the Gr-1 neutrophil marker and the Ym1 macrophage marker) was delayed in the DB wounds. Expression of the M2 macrophage-related genes, Ym1 and arginase 1, was significantly reduced in the DB wounds. PCR array analysis demonstrated altered cytokine expression in DB wounds. Most prominently, both interleukin (IL)-17 and IL-20 mRNA levels were significantly increased in the DB wounds. Innovation: This is the first study to identify increased levels of IL-17 and IL-20 in DB wounds. These cytokines are also elevated in the inflammatory skin disorder, psoriasis; thus, they may be potential therapeutic targets to aid in DB wound healing. Conclusion: The entire cytokine profile of DB wounds over the course of healing is not completely understood. This study suggests that the IL-17 and IL-20 families of cytokines should be further analyzed in the context of DB wound healing.

Antioxidative bioactive glass reinforced injectable hydrogel with reactive oxygen species scavenging capacity for diabetic wounds treatment

Hydrogel with ROS scavenging effect encapsulates BR@Zn-BTB nanoparticles for accelerating diabetic mice wound healing via multimodal therapy

A hydrogel crosslinked with mixed-valence copper nanoclusters for diabetic wound healing.

Targeting multiple mediators of sepsis using multifunctional tannic acid-Zn2+-gentamicin nanoparticles

Facile formation of injectable quaternized chitosan/tannic acid hydrogels with antibacterial and ROS scavenging capabilities for diabetic wound healing

Diabetic chronic wounds and amputations are very serious complications of diabetes mellitus (DM) that result from an integration factor, including oxygen deprivation, elevated reactive oxygen species (ROS), reduced angiogenesis, and microbial invasion. These causative factors lead to tenacious wounds in an inflammatory state, which eventually results in tissue aging and necrosis. Wound healing in DM potentially targets C-X-C chemokine receptor type 4 (CXCR4) regulates several signalling pathways. The CXCR4 signalling pathway integrated with phospholipase C (PLC)/protein kinase-C (PKC) Ca2+ pathways, stromal cell-derived factor-1 (SDF-1), and mitogen- activated protein kinases (MAPKs) pathway for enhancing cell chemotaxis, proliferation, and survival. The dysregulated CXCR4 pathway is connected with poor wound healing in DM patients. Therapeutic strategies targeting CXCR4-based molecules such as UCUF-728, UCUF-965, and AMD3100 have been shown to enhance diabetic wound healing by altering miRNA expression, promoting angiogenesis, and accelerating wound closure. This study indicates that CXCR4 participation in various signalling pathways makes it essential for understanding the healing of diabetic wounds. Using specific compounds to target CXCR4 offers a potentially effective treatment strategy to improve wound healing in diabetes. Our understanding of CXCR4 signalling and its regulation processes will enable us to develop more potent wound care solutions for diabetic chronic wounds. This report concludes that CXCR4's potential therapeutic targeting shows improvements in diabetic wound repair. This review will demonstrate that CXCR4 plays a major role in wound healing through its various signalling pathways. Targeting CXCR4 with certain agonist molecules shows a therapeutic approach to potentially increasing wound healing in diabetes. By enhancing our understanding of the CXCR4 signalling mechanism in future studies, we can develop more potential treatments for chronic diabetic wounds.

Glycopeptide-based multifunctional nanofibrous hydrogel that facilitates the healing of diabetic wounds infected with methicillin-resistant Staphylococcus aureus