Wound Inflammation Research Articles

Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1β Signaling Pathways.

Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1β, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.

Shikonin Inhibits Vascular Extravasation and Inflammation in Burn Wounds by Regulating Wnt/β-Catenin Pathway

Objective: To explore whether shikonin can alleviate vascular leakage in burn wounds, inhibit skin inflammation, and exert protective effects on skin. Methods: A mouse skin burn wound model was routinely established, and fluorescent microspheres were injected through the tail vein 2 h before sampling to characterize the degree of vascular leakage. Dorsal skin was obtained by surgical dissection and embedded in OCT, and frozen sections were prepared. CD31 immunofluorescence was used to determine the distribution of blood vessels in burnt skin, and Ly6G immunofluorescence staining was used to determine the level of neutrophil recruitment in the skin. Results: Skin microvessels were mainly distributed in the dermis. We found that severe vascular leakage occurred in the blood vessels of the burned dermis, and shikonin significantly alleviated vascular leakage in the burned area. Furthermore, shikonin significantly inhibited neutrophil recruitment to burn sites. Most importantly, we also found that shikonin can alleviate vascular leakage and inhibit skin inflammation at burn sites through the Wnt/β-catenin signaling pathway. Conclusion: Shikonin can alleviate vascular leakage, and inhibit skin inflammation in burn wounds through the Wnt/β-catenin signaling pathway. This experimental study provides a proof-of-concept and a new avenue for the repair and treatment of burn skin vascular injuries.

Correlational analysis of PLIN1 with inflammation in diabetic foot ulcer wounds

BackgroundThe persistent presence of inflammation is a recognized pathogenic mechanisms of diabetic foot ulcers (DFUs). We aimed to investigate the expression of PLIN1 in tissues from DFU patients and assess its potential association with inflammation-induced damage. MethodsWe performed transcriptome sequencing and correlation analysis of the foot skin from patients with or without DFUs. Additionally, we examined the correlation between PLIN1 and related inflammatory indicators by analyzing PLIN1 expression in tissue and serum samples and through high-glucose stimulation of keratinocytes (HaCaT cells). ResultsPLIN1 is upregulated in the tissue and serum from DFU patients. Additionally, PLIN1 shows a positive correlation with leukocytes, neutrophils, monocytes, C-reactive protein, and procalcitonin in the serum, as well as IL-1β and TNF-α in the tissues. Experiments with Cells demonstrated that reduced expression of PLIN1 leads to significantly decreased expression of iNOS, IL-1β, IL-6, IL-18, and TNF-α. PLIN1 may mediate wound inflammatory damage through the NF-κB signaling pathway. ConclusionOur findings suggest that PLIN1 mediates the inflammatory damage in DFU, offering new prospects for the treatment of DFU.

Investigating the Wound Healing Activity of Silymarin Nanoemulsion Loaded in Chitosan Gel

Wound healing is a complex biological process involving a series of coordinated cellular and molecular events to restore tissue integrity and functionality. Challenges in achieving optimal wound healing have prompted the search for innovative therapeutic strategies. In recent years, nanotechnology-based approaches have gained attention for their potential in promoting wound healing outcomes. Silymarin, a natural polyphenolic compound, possesses diverse therapeutic properties including anti-inflammatory, antioxidant, and wound healing effects. Loading these compounds in a chitosan-based nanoemulgel formulation enhances their stability, bioavailability, and targeted delivery to the wound site. In this study, we evaluated the efficacy of silymarin nanoemulsion-loaded chitosan gel (SLY-CS-NEG) through in vitro and in vivo experiments. The evaluation encompassed wound closure percentage, inflammation reduction, and tissue regeneration assessments. The selected formulation No (F6) of SLY-CS-NEG, boasted remarkable characteristics, with a mean droplet size of 49.94±0.21 nm, a negative surface charge of −29.9±0.61, and sustained drug release over the 24 h. Animal experiments unveiled that SLY-CS-NEG significantly promoted wound healing compared to the control group. The results of this study demonstrated that the nanomedicine-based approach utilizing chitosan and nanoemulsion technology presents an innovative solution to overcome the limitations of silymarin and advance wound healing therapies.

Hyaluronic acid in Dentoalveolar regeneration: Biological rationale and clinical applications

BackgroundHyaluronic acid (HA) is found in different locations in the periodontium, including mineralized tissues (i.e., cementum and alveolar bone) and non-mineralized tissues (i.e., gingiva and periodontal ligament). In addition, it seems to play an essential part in regulating the underlying mechanisms involved in tissue inflammatory reactions and wound healing. HA has the potential to regulate periodontal tissue regeneration and treat periodontal disease. AimThe current review of the literature was conducted to assess how HA plays its part in periodontal therapy and examine the contemporary literature's viewpoint on its use in periodontal regeneration. ConclusionHA has a multifunctional character in periodontal regeneration, and healing and appears to provide promising outcomes in different periodontal regenerative applications.

Composite nano hydrogel with dual response and hierarchical drug release for enhanced wound healing

A novel nanocomposite hydrogel with photothermal therapeutic properties, which could enhance the healing of surgical wounds, was developed. The composite comprises functionalized silica nanoparticles (FSNs) loaded with desferoxamine (DFO) as the core and a dexamethasone (Dex) filled hyaluronic acid–chitosan hydrogel (HA-CS) as the shell. Dex can effectively control inflammation at the wound site, and DFO is beneficial in proliferating the skin cells. The two drugs effectively promote wound healing at the surgical site. The aim of this approach is to demonstrate the hierarchical and continuous release of Dex and DFO from the FSNs@DFO-H@Dex system to reduce wound inflammation and promote healing. Furthermore, the controlled release of DFO can be achieved by controlling the near-infrared illumination. The composite nano hydrogel has a photothermal response, which accelerates wound healing by effectively reducing inflammation through the controlled release of drugs and regulating the immunological response of damaged skin tissue.

A rapid interactive chitosan-based medium with antioxidant and pro-vascularization properties for infected burn wound healing

Large-pore hydrogels are better suited to meet the management needs of nutrient transportation and gas exchange between infected burn wounds and normal tissues. However, better construction strategies are required to balance the pore size and mechanical strength of hydrogels to construct a faster substance/gas interaction medium between tissues. Herein, we developed spongy large pore size hydrogel (CS-TA@Lys) with good mechanical properties using a simple ice crystal-assisted method based on chitosan (CS), incorporating tannic acid (TA) and ε-polylysine (Lys). A large-pore and mechanically robust hydrogel medium was constructed based on hydrogen bonding between CS molecules. On this basis, a pro-restorative functional platform with antioxidation and pro-vascularization was constructed using TA and Lys. In vitro experiments displayed that the CS-TA@Lys hydrogel possessed favorable mechanical properties and fast interaction performances. In addition, the CS-TA@Lys hydrogel possessed the capacity to remove intra/extracellular reactive oxygen species (ROS) and possessed antimicrobial and pro-angiogenic properties. In vivo experiments displayed that the CS-TA@Lys hydrogel inhibited wound inflammation and promoted wound vascularization. In addition, the CS-TA@Lys hydrogel showed the potential for rapid hemostasis. This study provides a potential functional wound dressing with rapid interaction properties for skin wound repair.

Heparin-loaded hierarchical fiber/microsphere scaffolds for anti-inflammatory and promoting wound healing

Chronic non-healing wounds induced by oxidative stress and inflammation can activate inflammatory cells and produce large amounts of inflammatory mediators, which fail to maintain homeostasis in the skin and delay the wound-healing process. To tackle this issue, heparin-loaded hierarchical composite scaffolds comprised of electrospun fibers and electrosprayed microspheres were prepared to act as an effective anti-inflammatory wound dressing. Microspheres with different electrosprayed densities were deposited into the surface of the electrospun fibers for the improvement of surface topographical cues and cellular activities. The results indicated that the electrospun fibers followed by electrosprayed for 3 ​min to fabricate the composite fiber/microsphere scaffolds contributed to the best performance in terms of promoting cellular activities, with no obvious cytotoxicity, good adhesion morphology, and the fastest cell migration rate. In addition, a suitable amount of heparin was added to the composite scaffolds to alleviate inflammation. The significant adsorption efficiency of heparin-loaded composite scaffolds on inflammatory mediator MCP-1 indicates a favorable anti-inflammation effect in vitro. Furthermore, the heparin-loaded hierarchical scaffolds accelerated the pace of inflammatory wound healing in vivo when compared to commercial 3 ​M Tegaderm and non-heparin-loaded scaffolds. Our work provided a facile strategy for fabricating heparin-loaded hierarchical fiber/microsphere scaffolds to modulate cellular activities via topographical cues and accelerating the inflammatory wound healing process by electrostatic interactions between heparin and MCP-1. These findings suggested that the heparin-loaded hierarchical scaffold was expected to be a promising dressing for inflammatory wound healing.

Proteomic Profiling of Dilated Cardiomyopathy Plasma Samples ─ Searching for Biomarkers with Potential to Predict the Outcome of Therapy.

Determination of the prognosis and treatment outcomes of dilated cardiomyopathy is a serious problem due to the lack of valid specific protein markers. Using in-depth proteome discovery analysis, we compared 49 plasma samples from patients suffering from dilated cardiomyopathy with plasma samples from their healthy counterparts. In total, we identified 97 proteins exhibiting statistically significant dysregulation in diseased plasma samples. The functional enrichment analysis of differentially expressed proteins uncovered dysregulation in biological processes like inflammatory response, wound healing, complement cascade, blood coagulation, and lipid metabolism in dilated cardiomyopathy patients. The same proteome approach was employed in order to find protein markers whose expression differs between the patients well-responding to therapy and nonresponders. In this case, 45 plasma proteins revealed statistically significant different expression between these two groups. Of them, fructose-1,6-bisphosphate aldolase seems to be a promising biomarker candidate because it accumulates in plasma samples obtained from patients with insufficient treatment response and with worse or fatal outcome. Data are available via ProteomeXchange with the identifier PXD046288.

Characterization of cardiac fibroblast-extracellular matrix crosstalk across developmental ages provides insight into age-related changes in cardiac repair.

Heart failure afflicts an estimated 6.5 million people in the United States, driven largely by incidents of coronary heart disease (CHD). CHD leads to heart failure due to the inability of adult myocardial tissue to regenerate after myocardial infarction (MI). Instead, immune cells and resident cardiac fibroblasts (CFs), the cells responsible for the maintenance of the cardiac extracellular matrix (cECM), drive an inflammatory wound healing response, which leads to fibrotic scar tissue. However, fibrosis is reduced in fetal and early (<1-week-old) neonatal mammals, which exhibit a transient capability for regenerative tissue remodeling. Recent work by our laboratory and others suggests this is in part due to compositional differences in the cECM and functional differences in CFs with respect to developmental age. Specifically, fetal cECM and CFs appear to mitigate functional loss in MI models and engineered cardiac tissues, compared to adult CFs and cECM. We conducted 2D studies of CFs on solubilized fetal and adult cECM to investigate whether these age-specific functional differences are synergistic with respect to their impact on CF phenotype and, therefore, cardiac wound healing. We found that the CF migration rate and stiffness vary with respect to cell and cECM developmental age and that CF transition to a fibrotic phenotype can be partially attenuated in the fetal cECM. However, this effect was not observed when cells were treated with cytokine TGF-β1, suggesting that inflammatory signaling factors are the dominant driver of the fibroblast phenotype. This information may be valuable for targeted therapies aimed at modifying the CF wound healing response and is broadly applicable to age-related studies of cardiac remodeling.

Regulation of inflammation during wound healing: the function of mesenchymal stem cells and strategies for therapeutic enhancement.

A wound takes a long time to heal and involves several steps. Following tissue injury, inflammation is the primary cause of tissue regeneration and repair processes. As a result, the pathophysiological processes involving skin damage, healing, and remodeling depend critically on the control of inflammation. The fact that it is a feasible target for improving the prognosis of wound healing has lately become clear. Mesenchymal stem cells (MSCs) are an innovative and effective therapeutic option for wound healing due to their immunomodulatory and paracrine properties. By controlling the inflammatory milieu of wounds through immunomodulation, transplanted MSCs have been shown to speed up the healing process. In addition to other immunomodulatory mechanisms, including handling neutrophil activity and modifying macrophage polarization, there may be modifications to the activation of T cells, natural killer (NK) cells, and dendritic cells (DCs). Furthermore, several studies have shown that pretreating MSCs improves their ability to modulate immunity. In this review, we summarize the existing knowledge about how MSCs influence local inflammation in wounds by influencing immunity to facilitate the healing process. We also provide an overview of MSCs optimizing techniques when used to treat wounds.

Inflammasome modulation with P2X7 inhibitor A438079-loaded dressings for diabetic wound healing.

The inflammasome is a multiprotein complex critical for the innate immune response to injury. Inflammasome activation initiates healthy wound healing, but comorbidities with poor healing, including diabetes, exhibit pathologic, sustained activation with delayed resolution that prevents healing progression. In prior work, we reported the allosteric P2X7 antagonist A438079 inhibits extracellular ATP-evoked NLRP3 signaling by preventing ion flux, mitochondrial reactive oxygen species generation, NLRP3 assembly, mature IL-1β release, and pyroptosis. However, the short half-life in vivo limits clinical translation of this promising molecule. Here, we develop a controlled release scaffold to deliver A438079 as an inflammasome-modulating wound dressing for applications in poorly healing wounds. We fabricated and characterized tunable thickness, long-lasting silk fibroin dressings and evaluated A438079 loading and release kinetics. We characterized A438079-loaded silk dressings in vitro by measuring IL-1β release and inflammasome assembly by perinuclear ASC speck formation. We further evaluated the performance of A438079-loaded silk dressings in a full-thickness model of wound healing in genetically diabetic mice and observed acceleration of wound closure by 10 days post-wounding with reduced levels of IL-1β at the wound edge. This work provides a proof-of-principle for translating pharmacologic inhibition of ATP-induced inflammation in diabetic wounds and represents a novel approach to therapeutically targeting a dysregulated mechanism in diabetic wound impairment.

Blow-Spun Si3N4-Incorporated Nanofibrous Dressing with Antibacterial, Anti-Inflammatory, and Angiogenic Activities for Chronic Wound Treatment

The effective and safe healing of chronic wounds, such as diabetic ulcers, presents a significant clinical challenge due to the adverse microenvironment in the wound that hinders essential processes of wound healing, including angiogenesis, inflammation resolution, and bacterial control. Therefore, there is an urgent demand for the development of safe and cost-effective multifunctional therapeutic dressings. Silicon nitride, with its distinctive antibacterial properties and bioactivities, shows great potential as a promising candidate for the treatment of chronic wounds. In this study, a silicon nitride-incorporated collagen/chitosan nanofibrous dressing (CCS) were successfully fabricated using the solution blow spinning technique (SBS). SBS offers compelling advantages in fabricating uniform nanofibers, resulting in a three-dimensional fluffy nanofibrous scaffold that creates an optimal wound healing environment. This blow-spun nanofibrous dressing exhibits excellent hygroscopicity and breathability, enabling effective absorption of wound exudate. Importantly, the incorporated silicon nitride within the fibers triggers surface chemical reactions in the aqueous environment, leading to the release of bioactive ions that modulate the wound microenvironment. Here, the CCS demonstrated exceptional capabilities in absorbing wound exudate, facilitating water vapor transmission, and displaying remarkable antibacterial properties in vitro and in a rat infected wound model (up to 99.7%, 4.5 × 107 CFU/cm2 for Staphylococcus aureus). Furthermore, the CCS exhibited an enhanced wound closure rate, angiogenesis, and anti-inflammatory effects in a rat diabetic wound model, compared to the control group without silicon nitride incorporation.Graphical abstract

Injectable and Thermosensitive Hydrogel with Platelet-Rich Plasma for Enhanced Biotherapy of Skin Wound Healing.

The rapid and effective healing of skin wounds resulted from severe injuries and full-layer skin defects remains a pressing clinical challenge in contemporary medical practice. The reduction of wound infection and rapid healing is helpful to rebuild and repair skin tissue. Here, a thermosensitive chitosan-based wound dressing hydrogel incorporating β-glycerophosphate (GP), hydroxy propyl cellulose (HPC), graphene oxide (GO), and platelet-rich plasma (PRP) is developed, which exhibits the dual functions of antibacterial properties and repair promotion. GP and HPC enhance the mechanical properties through forming hydrogen bonding connection, while GO produces local heat under near-infrared light, leading to improved blood circulation and skin recovery. Notably, antibacterial properties against Pseudomonas aeruginosa, and control-release of growth factors from PRP are also achieved based on the system. In vitro experiments reveal its biocompatibility, and ability to promote cell proliferation and migration. Animal experiments demonstrate that the epithelial repair and collagen deposition can be promoted during skin wound healing in Sprague Dawley rats. Moreover, a reduction in wound inflammation levels and the improvement of wound microenvironment are observed, collectively fostering effective wound healing. Therefore, the composite hydrogel system incorporated with GO and PRP can be a promising dressing for the treatment of skin wounds.

Identification of the role of TG2 on the expression of TGF-β, TIMP-1 and TIMP-2 in aged skin

Abstract Objectives Transglutaminase 2 (TG2) is a unique protein having enzymatic and nonenzymatic functions that have been implicated in various biological and pathological processes such as cell survival and apoptosis, cell signaling, differentiation, adhesion and migration, wound healing and inflammation. As reported in previous studies, TG2 expression and activity increase by age suggesting that TG2 possibly has roles in cellular aging process. In this study, we aimed to explore the role of TG2 in chronological skin aging through its impact on the expression of some important extracellular matrix (ECM) proteins including TGF-β, TIMP-1 and TIMP-2. Methods We have compared TG2 expression and activity in young and in vitro chronologically aged human dermal fibroblasts via Western blot and in situ TG2 activity assays. Afterwards, we inhibited TG2 expression via siRNA transfection and activity via active site inhibitor of TG2 separately in aged dermal fibroblasts and monitored the expression levels of TGF-β, TIMP-1 and TIMP-2 in these cells by Western blot and compared to that of untreated control cells. Results We obtained evidence that both TG2 expression and activity increase in aged cells. However, protein levels of TGF-β, TIMP-1 and TIMP-2 do not exhibit any significant difference in TG2 downregulated or TG2 activity inhibited aged cells compared to control cells. Conclusions Our results indicate that changes in the expression and activity of TG2 in (in vitro) chronologically aged human dermal fibroblasts do not impact the expression patterns of TGF-β, TIMP-1 and TIMP-2 proteins.

3D-printed hydrogels based on amphiphilic chitosan derivative loaded with levofloxacin for wound healing applications

Skin wounds not only cause physical pain to patients but also pose an economic burden to society. Consequently, effective approaches to promote skin repair remain a challenge. Specifically, chitosan-based hydrogels are ideal candidates to promote wound healing at different stages and while diminishing the factors that impede this process (such as excessive inflammatory and chronic wound infection). Furthermore, the unique biological properties of a chitosan-based hydrogel enable it to serve as both a wound dressing and a drug delivery system (DDS). In the present work, chitosan (CS) graft copolymer with [2-(methacryloyloxy)ethyl] trimethyl ammonium chloride (CS-MTAC), a cationic monomer with promising antibacterial properties, was synthesized. The successful synthesis of the copolymer was confirmed, while it was studied for its swelling ability and water absorption capacity, as well as for its biocompatibility and antibacterial properties. Expecting to improve its printability, the copolymer was blended with elastin (EL), collagen (COL), and increasing concentrations of gelatin (GEL). The hydrogel with 6% w/v CS, 4% w/w EL, 4% w/w COL and 1% w/v GEL was selected for its potential to be 3D-printed and was neutralized with ammonia vapors or ethanol/sodium hydroxide solution and loaded with levofloxacin. The feasibility of CS-MTAC/EL/COL/GEL bioink, loaded with Levo, as a suitable candidate for wound healing and drug delivery applications, has been demonstrated.

Collagenase-based wound debridement agent induces extracellular matrix supporting phenotype in macrophages

Macrophages assume diverse phenotypes and functions in response to cues from the microenvironment. Earlier we reported an anti-inflammatory effect of Collagenase Santyl® Ointment (CSO) and the active constituent of CSO (CS-API) on wound macrophages in resolving wound inflammation indicating roles beyond debridement in wound healing. Building upon our prior finding, this study aimed to understand the phenotypes and subsets of macrophages following treatment with CS-API. scRNA-sequencing was performed on human blood monocyte-derived macrophages (MDM) following treatment with CS-API for 24 h. Unbiased data analysis resulted in the identification of discrete macrophage subsets based on their gene expression profiles. Following CS-API treatment, clusters 3 and 4 displayed enrichment of macrophages with high expression of genes supporting extracellular matrix (ECM) function. IPA analysis identified the TGFβ-1 pathway as a key hub for the CS-API-mediated ECM-supportive phenotype of macrophages. Earlier we reported the physiological conversion of wound-site macrophages to fibroblasts in granulation tissue and impairment of such response in diabetic wounds, leading to compromised ECM and tensile strength. The findings that CSO can augment the physiological conversion of macrophages to fibroblast-like cells carry significant clinical implications. This existing clinical intervention, already employed for wound care, can be readily repurposed to improve the ECM response in chronic wounds.

Deferiprone-Gallium-Protoporphyrin Chitogel Decreases Pseudomonas aeruginosa Biofilm Infection without Impairing Wound Healing.

Pseudomonas aeruginosa is one of the most common pathogens encountered in clinical wound infections. Clinical studies have shown that P. aeruginosa infection results in a larger wound area, inhibiting healing, and a high prevalence of antimicrobial resistance. Hydroxypyridinone-derived iron chelator Deferiprone (Def) and heme analogue Gallium-Protoporphyrin (GaPP) in a chitosan-dextran hydrogel (Chitogel) have previously been demonstrated to be effective against PAO1 and clinical isolates of P. aeruginosa in vitro. Moreover, this combination of these two agents has been shown to improve sinus surgery outcomes by quickly reducing bleeding and preventing adhesions. In this study, the efficacy of Def-GaPP Chitogel was investigated in a P. aeruginosa biofilm-infected wound murine model over 6 days. Two concentrations of Def-GaPP Chitogel were investigated: Def-GaPP high dose (10 mM Def + 500 µg/mL GaPP) and Def-GaPP low dose (5 mM Def + 200 µg/mL GaPP). The high-dose Def-GaPP treatment reduced bacterial burden in vivo from day 2, without delaying wound closure. Additionally, Def-GaPP treatment decreased wound inflammation, as demonstrated by reduced neutrophil infiltration and increased anti-inflammatory M2 macrophage presence within the wound bed to drive wound healing progression. Def-GaPP Chitogel treatment shows promising potential in reducing P. aeruginosa cutaneous infection with positive effects observed in the progression of wound healing.

Role of TGF-β3 in modulating inflammatory responses and wound healing processes in ischemic ulcers in atherosclerotic patients.

Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF-β3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF-β3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross-sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF-β3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF-β3, pro-inflammatory and anti-inflammatory markers. A subset of patients were administered topical TGF-β3 in order to evaluate its therapeutic effects. The expression pattern of TGF-β3 was found to be stage-dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF-β3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF-β3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF-β3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF-β3, which functions as an anti-inflammatory and pro-inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent.

Photothermal-enhanced in situ supramolecular hydrogel promotes bacteria-infected wound healing in diabetes.

Bacterial infection can impede the healing of chronic wounds, particularly diabetic wounds. The high-sugar environment of diabetic wounds creates a favorable condition for bacterial growth, posing a challenge to wound healing. In clinical treatment, the irregular shape of the wound and the poor mechanical properties of traditional gel adjuvants make them susceptible to mechanical shear and compression, leading to morphological changes and fractures, and difficult to adapt to irregular wounds. Traditional gel adjuvants are prepared in advance, while in situ gel is formed at the site of administration after drug delivery in a liquid state, which can better fit the shape of the wound. Therefore, this study developed an in situ HA/GCA/Fe2+-GOx gel using a photothermal-enhanced Fenton reaction to promote the generation of hydroxyl radicals (·OH). The generation of ·OH has an antibacterial effect while promoting the formation of the gel, achieving a dual effect. The addition of double-bonded adamantane (Ada) interacts with the host-guest effect of graphene oxide and the double-bond polymerization of HAMA gel, making the entire gel system more complete. At the same time, the storage modulus (G') of the gel increased from 130 to 330Pa, enhancing the mechanical properties of the gel. This enables the gel to have better injectability and self-healing effects. The addition of GOx can consume glucose at the wound site, providing a good microenvironment for the repair of diabetic wounds. The gel has good biocompatibility and in a diabetic rat wound model infected with S. aureus, it can effectively kill bacteria at the wound site and promote wound repair. Meanwhile, the inflammation of wounds treated with HA/GCA/Fe2+-GOx+NIR was lighter compared to untreated wounds. Therefore, this study provides a promising strategy for treating bacterial-infected diabetic wounds.