Wound Healing Process Research Articles

Antibacterial Biocomposite Based on Chitosan/Pluronic/Agarose Noncovalent Hydrogel: Controlled Drug Delivery by Alginate/Tetracycline Beads System.

Designing a wound dressing with controlled uptake, antibacterial, and proper biocompatibility is crucial for the appropriate wound healing process. In this study, alginate/tetracycline (Alg/TC) beads were produced and embedded into chitosan/pluronic/agarose semi-interpenetrating polymer network hydrogel, which serves as a potential biocompatible dressing for treating skin wounds. The effect of pluronic content on the porosity, swelling, mechanical characteristics, and degradation of the hydrogel was investigated. Furthermore, the impact of Alg beads on TC release was subsequently examined. In the absence of Alg beads, faster release was observed. However, after incorporating beads into the hydrogels, the release was sustained. Particularly, the hydrogel containing Alg beads exhibited a nearly linear release, reaching 74% after 2 days in acidic media. The antimicrobial activity and biocompatibility of the hydrogel were also evaluated to assess the capability of the TC-loaded hydrogels for wound dressing applications. The hydrogel demonstrated efficient antibacterial features against Gram-positive and Gram-negative bacteria. Additionally, the sample behavior was evaluated against exposure to yeast. Furthermore, based on biocompatibility studies using HFF2 cells, the TC-loaded hydrogel exhibited remarkable biocompatibility. Overall, this novel composite hydrogel shows remarkable biocompatibility and antibacterial activities which can be used as a great potential wound dressing to prevent wound infections due to its effective inhibition of bacterial growth.

The Wound-Healing Effect of a Novel Fibroblasts-Impregnated Hydroxyethylcellulose Gel in a Rat Full-Thickness Burn Model: A Preclinical Study.

Background/Objectives: The objective of this study was to assess the efficacy of a cell-containing wound dressing based on fibroblasts in hydroxyethylcellulose (HEC) gel for the local treatment of deep partial-thickness and/or full-thickness skin burns in an animal model. Methods: The rats (male Wistar, n = 100) were subjected to a full-thickness thermal burn (16 cm2). Radical necrectomy was performed one day after the burn. Three days later, the rats were randomly assigned to one of four groups: group 1 (no treatment), group 2 (chloramphenicol and methyluracil ointment, a routine clinical treatment), group 3 (a gel without cells, mock treatment), and group 4 (a dermal fibroblast-impregnated HEC gel). The treatment lasted for five days. The wound-healing process was evaluated by planimetric, cytologic, histologic, and immunohistochemical methods. Results: The differences in the rate of wound healing and the characteristics of wound cytology were identified. In the group 4, a regenerative type of cytogram was revealed, characterized by a significantly increased number of fibroblastic cells in comparison to samples from non-treated and mock-treated animals. Biopsy samples of burn wounds from animals in the group 4l demonstrated the presence of mature granulation tissue and a large number of microvessels. The repair process was stimulated, as evidenced by the increased thickness of newly formed granulation tissue and epidermis in the wound zone, elevated cellularity, and enhanced re-epithelialization activity. The number of Ki-67-positive proliferating cells was significantly higher in group 4 than in the control groups). A small number of non-proliferating donor fibroblasts was observed in the wound area 3 days after the end of treatment. Conclusions: The cell product is an effective agent for promoting wound healing during the regenerative phase. The experiments demonstrated that a gel populated by dermal fibroblasts can stimulate reparative regeneration processes in deep partial- and full-thickness burn wounds.

Impact of Epigenetics, Diet, and Nutrition-Related Pathologies on Wound Healing.

Chronic wounds pose a significant challenge to healthcare. Stemming from impaired wound healing, the consequences can be severe, ranging from amputation to mortality. This comprehensive review explores the multifaceted impact of chronic wounds in medicine and the roles that diet and nutritional pathologies play in the wound-healing process. It has been well established that an adequate diet is crucial to proper wound healing. Nutrients such as vitamin D, zinc, and amino acids play significant roles in cellular regeneration, immune functioning, and collagen synthesis and processing. Additionally, this review discusses how patients with chronic conditions like diabetes, obesity, and nutritional deficiencies result in the formation of chronic wounds. By integrating current research findings, this review highlights the significant impact of the genetic make-up of an individual on the risk of developing chronic wounds and the necessity for adequate personalized dietary interventions. Addressing the nutritional needs of individuals, especially those with chronic conditions, is essential for improving wound outcomes and overall patient care. With new developments in the field of genomics, there are unprecedented opportunities to develop targeted interventions that can precisely address the unique metabolic needs of individuals suffering from chronic wounds, thereby enhancing treatment effectiveness and patient outcomes.

Clinical and histological study of cold physical plasma jet in treatment of full thickness skin wounds of normal and diabetic dogs.

To study the effect of physical plasma jet in treating open wounds in diabetic and non-diabetic dogs. The experimental study was conducted at the College of Veterinary Medicine, University of Baghdad, Iraq, from 20 January, 2020 to 1st May 2020, according to (no. 1364/ P.G), and comprised adult male diabetic and nondiabetic dogs. They were divided into non-diabetic group N and diabetic group D. Each group was further divided into treatment subgroup T and control subgroup C. Each dog was subjected to 4 wounds 3×3cm in size. Homemade helium non-equilibrium atmospheric pressure plasma jet therapy was used for healing purposes. Clinical parameters were evaluated by observation, while histological images were scored based on the semi-quantitative evaluation of histological sections on days 3-, 7- and 21-days post-wound. Data was analysed using SPSS Version 26 with One-way ANOVA for statistical analysis between groups and sub-groups. Of the 24 dogs, 12(50%) were in each of the two groups, which were further divided into subgroups having 6(50%) dogs each. The therapy accelerated the process of wound healing in the NT and DT subgroups compared to NC and DC. Clinical observations revealed early and complete closure of plasma-treated wounds in NT and DT subgroups started at day 30 post-wounding, while in the NC subgroup it started at day 35, and in the DC subgroup, wounds failed to close even after 35 days post-wounding. Histological analysis suggested that a plasma jet supported epithelisation, angiogenesis, formation of new hair follicles and collagen fibres, while it also controlled inflammation. In addition, in NT and DT subgroups, it increased the proliferation of fibroblasts and deposition of collagen, and there is a very, highly significant difference between groups (P<0.001), and a significant difference between days (P<0.05). Home-made helium non-equilibrium atmospheric pressure plasma jet therapy improved the quality and pace of wound healing.

Dynamics of Burn Wound Healing in Children: Dependence on Anthropometric Parameters

Thermal trauma among pediatric patients has remained the leading cause of hospitalization in pediatric surgery departments in recent decades. Anthropometric parameters are often used by doctors when performing a comprehensive assessment of the child's physical development, and can also be used as essential factors in predicting the course of the disease. The aim of the study was to assess the dynamics of burn wound healing and its relationship with anthropometric parameters in individuals of the first period of childhood. Material and methods. The study involved investigation of the wound healing process in 125 male children, aged 4–6, having different levels of physical development. The patients' height, body weight (with calculation of the body mass index), head, chest and waist circumferences were measured on the day of admission using a standard set of anthropometric instruments, the WHtR index (waist to height ratio), and the head to chest ratio was calculated. Based on the BMI parameters, patients were divided into two groups: with normal weight and overweight. The wound area was measured on the 1st, 3rd, 5th, 7th and 9th days using the stereometric technique, applying a polyethylene antiseptic-processed film to the wound surface; this followed by outlining the edges of the wound defect. The results were processed using nonparametric statistics. Results It was found that in overweight patients, all the studied parameters, except for the ratio of head circumference to chest circumference, were higher than in children with the normal body weight. Correlations were detected between a number of anthropometric parameters in patients of both groups. On the 7th day, 73.9% of children with the normal body weight demonstrated epithelialization of the wound defect over the entire surface area of the wound, while in overweight children this was observed only in 34% of cases. Conclusion. As demonstrated, we obtained anthropometric measurements in boys of the first period of childhood having normal and overweight body weight. In children with the normal body weight, the process of wound epithelialization was completed mainly on the 7th day, while in patients with excess body weight, the wound defect closed by the 9th day. Excess body weight in children has a statistically significant relationship with an increased healing time of burn wounds.

Cancer Cell-Selective Inhibition of Migration by Styrenic Catiomer Emulsions.

Cancer metastasis remains the most formidable cause of mortality and morbidity in cancer patients. Developing an effective and economical method toward cancer antimetastatic strategy demands immediate attention in anticancer therapy. Herein, we followed a cost-effective greener method for preparing a small family of amphiphilic catiomers with varied styrene content (45, 63, and 83%), which revealed the unique potential of promoting normal cell migration while retarding cancer metastasis. The styrenic polymers formed micellar self-assembly in aqueous phase and exhibited a cationic charge. Polymers were quite nontoxic up to 200 μg/mL concentration toward human embryonic kidney cell HEK293 as well as human, triple negative breast cancer cell MDAMB-231, mouse melanoma cell B16F10, and human oral squamous carcinoma cell FaDu. Confocal imaging and fluorescence activated cell sorting (FACS) showed effective incorporation of polymers within cells. Interestingly, the polymer-treated HEK293 cells underwent prominent wound healing in scratch assay. However, the as-synthesized polymer-treated cancer cells resisted migration as analyzed from the scratch assay. A mechanistic study using immunoblotting assay established upregulation of migratory proteins vimentin and TGF-β and downregulation of E-cadherin in normal HEK293 cells. Remarkably, this trend was completely reversed in cancer cell MDAMB-231. This study describes the extraordinary potential of styrenic catiomers as wound healers for normal cells while inhibiting cancer metastasis.

Immunomodulation of Macrophages in Diabetic Wound Individuals by Structurally Diverse Bioactive Phytochemicals

Diabetes-related ulcers and slow-healing wounds pose a significant health risk to individuals due to their uncertain causes. Mortality rates for diabetes foot ulcers (DFUs) range from 10% after 16 months to 24% after five years. The use of bioactive phytochemicals can play a key role in healing wounds in a predictable time. Recent literature has demonstrated that various natural substances, including flavonoids, saponins, phenolic compounds, and polysaccharides, play key roles at different stages of the wound-healing process through diverse mechanisms. These studies have categorized the compounds according to their characteristics, bioactivities, and modes of action. In this study, we evaluated the role of natural compounds derived from plant sources that have been shown to play a crucial role in immunomodulation. Macrophages are closely involved in immunomodulation within the wound microenvironment and are key players in efferocytosis, inflammation resolution, and tissue regeneration, all of which contribute to successful wound healing. Phytochemicals and their derivatives have shown capabilities in immune regulation, including macrophage migration, nitric oxide synthase inhibition, lymphocyte and T-cell stimulation, cytokine activation, natural killer cell enhancement, and the regulation of NF-κβ, TNF-α, and apoptosis. In this review, we have studied the role of phytochemicals in immunomodulation for the resolution of diabetic wound inflammation.

Quercus glauca Acorn Seed Coat Extract Promotes Wound Re-Epithelialization by Facilitating Fibroblast Migration and Inhibiting Dermal Inflammation.

The skin, recognized as the largest organ in the human body, serves a vital function in safeguarding against external threats. Severe damage to the skin can pose significant risks to human health. There is an urgent requirement for safe and effective therapies for wound healing. While phytotherapy has been widely utilized for various health conditions, the potential of Quercus glauca in promoting wound healing has not been thoroughly explored. Q. glauca is a cultivated crop known for its abundance of bioactive compounds. This study examined the wound-healing properties of Quercus glauca acorn seed coat water extract (QGASE). The findings from the study suggest that QGASE promotes wound closure in HF cells by upregulating essential markers related to the wound-healing process. Additionally, QGASE demonstrates antioxidant effects, mitigating oxidative stress and aiding in recovery from injuries induced by H2O2. In vivo experiments provide additional substantiation supporting the efficacy of QGASE in enhancing wound healing. The collective results indicate that QGASE may be a promising candidate for the development of innovative therapeutic strategies aimed at enhancing skin wound repair.

Three-dimensional bioprinted cell-adaptive hydrogel with anisotropic micropores for enhancing skin wound healing

Engineered matrices with aligned microarchitectures are pivotal in regulating the fibroblast-to-myofibroblast transition, a critical process for wound healing and scar reduction. However, developing a three-dimensional (3D) aligned matrix capable of effectively controlling this transition remains challenging. Herein, we developed a cell-adaptive hydrogel with highly oriented microporous structures, fabricated through bioprinting of thermo/ion/photo-crosslinked gelatin methacrylate/sodium alginate (GelMA/SA) incorporating shear-oriented polyethylene oxide (PEO) filler. The synergistic interactions among GelMA, PEO, and SA yield a homogeneous mixture conducive to the printing of biomimetic 3D constructs with anisotropic micropores. These anisotropic micropores, along with the biochemical cues provided by the GelMA/PEO/SA scaffolds, enhance the oriented spreading and organization of fibroblasts. The resultant spread and aligned cellular morphologies promote the transition of fibroblasts into myofibroblasts. By co-culturing human keratinocytes on the engineered dermal layer, we successfully create a bilayer skin construct, wherein the keratinocytes establish tight junctions accompanied by elevated expression of cytokeratin-14, while the fibroblasts display a highly spread morphology with increased fibronectin expression. The printed hydrogels accelerate full-thickness wound closure by establishing a bioactive microenvironment that mitigate inflammation and stimulate angiogenesis, myofibroblast transition, and extracellular matrix remodeling. This anisotropic hydrogel demonstrates substantial promise for applications in skin tissue engineering.

Assessment of the effect of ascorbic acid, sodium isoascorbate and calcium ascorbate treatments on the browning and wound healing process of fresh-cut potatoes

Browning significantly affects consumer perception, while texture hardening due to wound healing further reduces the commercial value of fresh-cut potatoes. This study evaluated the effects of 5 g L−1 ascorbic acid (AA), sodium isoascorbate (SI), and calcium ascorbate (CA) on browning and wound healing during ambient storage. The results indicated that AA and SI were more effective than CA and the control in delaying browning and wound healing. By day 3, browning levels in the AA and SI groups were reduced to 65 % and 62 % of the control, respectively, while lignin content decreased by 35 % and 40 %. Additionally, AA and SI treatments reduced reactive oxygen species (ROS) and improved antioxidant capacity, preserving appearance and texture. This study provides insights into the mechanisms of browning and wound healing, suggesting potential strategies for extending the shelf life and improving the quality of fresh-cut potatoes.

Combined Stromal Vascular Fraction and Fractional CO2 Laser Therapy for Hypertrophic Scar Treatment: A Systematic Review and Meta-Analysis.

Hypertrophic scars (HTSs) result from aberrant wound healing processes, leading to raised, thickened tissue with functional discomfort and cosmetic concerns. Current treatments, including corticosteroid injections and laser therapy, have limitations. Stromal vascular fraction (SVF) therapy and CO2 laser treatment offer promising avenues, with SVF therapy showing regenerative potential and CO2 laser therapy promoting precise tissue removal and wound healing. This study aims to investigate the combined application of SVF therapy and CO2 laser treatment for HTS, aiming to enhance treatment efficacy, tissue remodeling, and aesthetic outcomes, ultimately improving patient satisfaction in HTS management. PubMed, Scopus, Embase, and Web of Science databases have been searched for relevant studies. The "R" software (version 4.3.1) along with the "tidyverse" and "meta" statistical packages utilized to analyze data related to the efficiency of this combined method. A random-effects model was fitted to the data. For each study, continuous outcomes were pooled by calculating the standardized mean difference, along with their 95% confidence intervals. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. Six articles fulfilled our inclusion criteria and were included in our review. Results from the pooled analysis of Vancouver Scar Scale (VSS) scores across three included studies indicated a significant impact of the SVF+CO2 method on VSS scores post-treatment (SMD=-3.0144; 95% CI:-4.3706 to -1.6583, p<0.0001). However, analysis of transepidermal water loss levels before and after treatment showed no significant difference (SMD=-2.7603; 95% CI: -6.8729 to 1.3522; p=0.1883). Comparatively, in a pooled analysis of two studies, the combined SVF+CO2 method demonstrated superior efficacy in VSS scores compared to other methods (SMD= -1.3573; 95% CI: -2.2475 to -0.4672, p = 0.0028), with moderate heterogeneity across studies (I^2=23.0%, p = 0.2545). The combined application of SVF and CO2 laser treatment shows significant promise in improving hypertrophic scars' appearance and texture. The SVF+CO2 method demonstrates superior efficacy compared to other modalities, suggesting its potential as a valuable therapeutic approach for hypertrophic scar management. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Production and Characterization of Electrospun Chitosan, Nanochitosan and Hyaluronic Acid Membranes for Skin Wound Healing.

The development of new wound dressings made from biomaterials, which offer a better cost-benefit ratio and accelerate the healing process, is increasing nowadays. Various biopolymers can be electrospun to form functional membranes for wound healing. Therefore, in this study, chitosan and nanochitosan membranes with or without hyaluronic acid were prepared using the electrospinning technique, characterized and evaluated in the healing of skin wounds in rats. Chitosan and nanochitosan solutions, with or without hyaluronic acid, were prepared at concentrations of 1%-4% using PEO (polyethylene oxide) and subjected to the electrospinning process to obtain membranes characterized by scanning electron microscopy (SEM), mechanical tests, and antimicrobial activity. The healing effect of the membranes was evaluated by monitoring the area of the lesions, contraction of the wounds, histologic analysis, and induction of pro-inflammatory cytokine (IL-1 α and TNF-α) production in rats. The nanochitosan and nanochitosan membranes with hyaluronic acid achieved greater fiber diameter and uniformity, resistance, elasticity, and thermal stability, in addition to good adhesion to the wound bed and permeation capacity. Despite not presenting antimicrobial activity in vitro, they contributed to the production of pro-inflammatory interleukins in the animals tested, provided physical protection, reduced the wound area more markedly until the seventh day of the evaluation, with an acceleration of the healing process and especially when functionalized with hyaluronic acid. These results indicate that the membranes may be promising for accelerating the healing process of chronic wounds in humans.

Efficacy of Avocado Oil Cream in Wound Repair: Macroscopic Analysis, Inflammatory Cells Count, and Collagen Density

The wound healing process goes through a series of complex stages that are mutually continuous, namely inflammation, proliferation, and maturation. Following wound formation and the release of proinflammatory cytokines and growth factors, inflammation occurs immediately after the hemostasis phase. Proliferation occurs when products processed by the growth factors are present. The final stage, maturation, is portrayed by the plan of the extracellular network. This study utilized oil from avocado fruit (Persea americana), which contains linoleic and oleic acid content that supports skin tissue repair. The study aimed to explore the effects of using avocado oil cream on the area of wound healing, the number of inflammatory cells, and the collagen density. Twenty-four female mice, aged eight weeks, were used as experimental animals by making excision wounds using a 4 mm biopsy punch on the dorsal skin on the left and right sides. The mice were divided into four groups based on the percentage of avocado oil in the topical cream included Group K (control, topical cream without avocado oil), Group P1 (5% topical avocado oil cream), Group P2 (10% topical avocado oil cream), and Group P3 (15% topical avocado oil cream). Macroscopic examination of the wounds was conducted daily on days 3, 6, and 9 after topical cream treatment using a digital caliper. A total of 48 skin tissue samples were collected from days 3, 6, and 9 after cream application, which were then processed for histopathology evaluations using hematoxylin-eosin staining and Masson’s Trichrome staining. Hematoxylin-eosin staining was used to count the inflammatory cells, and Masson's Trichrome staining was employed to assess collagen density. The results revealed that avocado oil had a great impact on wound closure after 9 days of 15% avocado oil cream treatment, reducing the inflammatory cells after 3-6 days of 10% avocado oil cream therapy, and increasing collagen density after 9 days of 15% avocado oil cream application, as compared to the control, non-avocado oil cream group. Avocado oil can help close wounds, reduced the number of inflammatory cells, and increased collagen density when used in topical pharmaceutical formulations. Avocado oil cream may, therefore, be considered a viable option for wound repair treatment.

Effect of Aloe vera Gel and Sodium Metabisulphite on Expression of Fibroblast Growth Factor in Incision Wound of Rats

An incision wound is a wound caused by being sliced. Two ingredients that play a key role in the wound-healing process are glucomannan and acemannan, which are rich in polysaccharides and growth hormones. Growth hormones stimulate fibroblast activity and proliferation. The present study involved 35 Sprague Dawley male rats, aged 2-3 months old and weighing 200-300 grams. The study comprised seven groups including, negative control group (G1), positive control (aquades, G2), betadine 10% (G3), gel base (0.5 mg, G4), gel base + sodium metabisulfite 0.2 gr (G5), gel base + Aloe vera 5% (G6), and gel base + Aloe vera 5% + sodium metabisulfite 0.2 gr (G7). Each group had five replications. Initially, a 4-cm incision was made on the dorsal skin of each rat. The study lasted 15 days with observations made on days 3, 7, and 15. After the observation period, the rats were anesthetized and then terminated to collect skin tissues for microscopic examination. The tissue samples were then stained immunohistochemically to assess fibroblast growth factor (FGF) expressions. The results showed that the highest FGF expression was observed in the 5% Aloe vera + 2% metabisulfite group (G7), while the lowest FGF expression was in the negative control group (G1). It is concluded that Aloe vera L. extract gel at 5% + 2% metabisulfite (G7) significantly enhances the expression of FGF. Keywords: Aloe vera L, Fibroblast growth factor, Incision wound, Skin, Sodium metabisulfite

Morphological analysis of wound healing with the use of aloe extract, hydrogel and their combination (experimental research)

BACKGROUND: Currently, there remains a high incidence of skin damage due to trauma, chronic diseases, burns, so it is important to study the issues of regeneration and treatment of skin wounds. AIM: Conduct a morphological analysis of wound healing when using aloe extract, hydrogel and their combination in the experiment. METHODS:. The subjects of the study were 40 mature guinea pigs, which were divided into control and 4 experimental groups (independent wound healing, application of aloe extract, hydrosorb gel, layer-by-layer application of drugs). Histological skin preparations were prepared on days 7, 14, and 28 of the experiment. In each microslide, in 10 fields of view of the microscope at a magnification of x50, morphometric parameters were measured in micrometers (µm): the thickness of the purulent-necrotic scab, inflammatory (leukocyte) infiltrate, granulation tissue, the length of the newly formed epithelium on days 7, 14; the thickness of the epithelium, its length and the thickness of the connective tissue in the central part of the regenerate on the 28th day. All data were subjected to statistical processing. RESULTS: The use of drugs led to a decrease in the inflammatory reaction, acceleration of the formation of granulation tissue, and partial epithelization of the wound by the 7th day of the experiment, however, more pronounced signs of wound healing were observed with layer-by-layer application of aloe extract and hydrogel. The use of medications, regardless of the method of application, showed signs of more effective wound healing by day 14. Thus, the length of the epithelium increased by 1.2-1.6 times, the depth of granulation tissue by 1-1.2 times compared to the control. By the end of the experiment, all animals had complete closure of the wound defect with the formation of a scar, but in the experimental groups of the study there were signs of remodeling of the skin with appendages. CONCLUSION: Morphological analysis showed that the use of aloe extract, hydrosorb gel and their combination accelerates the wound healing processes of full-thickness skin wounds in the experiment.

Application of self powered black phosphorus nanosheets-based hydrogel skin patch in wound healing of diabetes

Diabetes mellitus-related chronic non-healing wounds have greatly lowered the quality of life for people afflicted and placed a heavy financial burden on the healthcare system. In order to hasten the healing of diabetic wounds, a wearable hydrogel-based triboelectric nanogenerator (BP-TENG) was created as a skin patch, which combines the beneficial effects of electrical and photothermal stimulation. The triboelectric output performance of the BP-TENG was adjusted and photothermal conversion capacity was brought about by the black phosphorus nanosheets (BPNS) doped in PVA hydrogel. In just 60 seconds, BP-TENG managed to bring the temperature of the mouse wound region up to 48.6°C under the irradiation of 808 nm near-infrared light. BP-TENG also exhibited spectral antibacterial activity against E. coli, S. aureus, and P. aeruginosa. Furthermore, BP-TENG had the ability to capture the energy from mechanical movements of mice and transform it into electrical stimulation. Under 808 nm near-infrared light irradiation, BP-TENG was shown to significantly speed the healing of skin wounds in the incision mouse model of type I diabetes. According to in vitro research, these benefits may be ascribed to photothermal and electric stimulation, which can both repair the healthy microenvironment of wound area and speed up the deposition and remodeling of collagen during the healing process of diabetic wounds. As far as we are aware, this is the first report on the creation and use of hydrogel-based TENG doped with BP for wound healing. We believe that this study improves the quality of life for patients with persistent non-healing wounds and opens up new possibilities for 2D materials and TENG in the application of wearable healthcare devices.

Immunomodulatory hydrogel orchestrates pro-regenerative response of macrophages and angiogenesis for chronic wound healing

Chronic wound healing often encounters challenges characterized by prolonged inflammation and impaired angiogenesis. While the immune response plays a pivotal role in orchestrating the intricate process of wound healing, excessive inflammation can hinder tissue repair. In this study, a bilayer alginate hydrogel system encapsulating polyelectrolyte complex nanoparticles (PCNs) loaded with anti-inflammatory cytokines and angiogenic growth factors is developed to address the challenges of chronic wound healing. The alginate hydrogel is designed using two distinct crosslinking methods to achieve differential degradation, thereby enabling precise spatial and temporal controlled release of PCNs. Initially, interleukin-10 (IL-10) is released to mitigate inflammation, while unsaturated PCNs bind and remove accumulated pro-inflammatory cytokines at the wound site. Subsequently, angiogenic growth factors, including vascular endothelial growth factor and platelet-derived growth factor, are released to promote vascularization and vessel maturation. Our results demonstrate that the bilayer hydrogel exhibits distinct degradation kinetics between the two layers, facilitating the staged release of multiple signaling molecules. In vitro experiments reveal that IL-10 can activate the Jak1/STAT3 pathway, thereby suppressing pro-inflammatory cytokines and chemokines while down-regulating inflammation-related genes. In vivo studies demonstrate that application of the hydrogel in chronic wounds using diabetic murine model promotes healing by positively modulating multiple integral reparative mechanisms. These include reducing inflammation, promoting macrophage polarization towards a pro-regenerative phenotype, enhancing keratinocyte migration, stimulating angiogenesis, and expediting wound closure. In conclusion, our hydrogel system effectively mitigates inflammatory responses and provides essential physiological cues by inducing a synergistic angiogenic effect, thus offering a promising approach for the treatment of chronic wounds.

Dialdehyde cellulose nanofibrils/polyquaternium stabilized ultra-fine silver nanoparticles for synergistic antibacterial therapy

Dialdehyde cellulose nanofibrils (DACNF) and Polyquaternium-10 (PQ: chloro-2-hydroxy-3-(trimethylamino) propyl polyethylene glycol cellulose) have become increasingly favored as antibacterial substances due to their advantageous characteristics. DACNF exhibits exceptional mechanical properties and biocompatibility, whereas PQ demonstrates a positive charge that enhances its antibacterial activity. Combined in a DACNF/PQ mixture, they provide an excellent template material for preparing and stabilizing ultra-fine (~ 10.3 nm) silver nanoparticles (AgNPs) at room temperature. Here, the dialdehyde group of DACNF functions as a reducing agent, while the quaternary ammonium of PQ and carboxylate groups of DACNF synergistically helped in-situ generation of AgNPs uniformly. The synthesized nanocomposites, namely PQ@AgNPs, AgNPs@DACNF, and AgNPs@DACNF/PQ, were subjected to comprehensive characterization using various advanced analytical techniques. The films containing AgNPs@DACNF and AgNPs@DACNF/PQ, fabricated via vacuum filtration, exhibited excellent mechanical properties of 9.78 ± 0.21 MPa, and demonstrated superior antibacterial activity against both Escherichia coli and Staphylococcus aureus. Additionally, the silver ion leaching from the prepared composite films was well controlled. The fabricated nanocomposites also effectively inhibited bacterial biofilm formation. It was also found to be highly biocompatible and non-toxic to human skin fibroblast cells. Furthermore, the nanocomposites exhibited enhanced migration of human dermal fibroblasts, suggesting their potential in facilitating wound healing processes.

A three-dimensional printable conductive composite dressing for accelerating wound healing under electrical stimulation

In this study, a bioink based on poly(vinyl alcohol) (PVA) and κ-carrageenan network was prepared using conductive polymer (PEDOT:PSS) as conducting medium, and (+)-Catechin-loaded mesoporous ZnO (CmZnO) as antibacterial and anti-inflammatory active medium. 3D conductive composite dressing was further fabricated by an extrusion 3D printing technology. Our results showed that the as-obtained composite dressing had suitable conductivity, efficient blood clotting capacity, and good adhesiveness. It also showed that the as-fabricated conductive composite had 92.9 % and 95.6 % antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively. Furthermore, the conductive dressing with an optimal electrical stimulation (ES) parameter showed in vivo blood clotting capacity, and it enhanced in vivo wound healing process in a full-thickness skin defect model than commercial dressings by upregulating the gene expression of growth factors including CD-31 and downregulating inflammatory factor expression of IL-6.

Encapsulation of Mentha aquatica methanol extract in alginate hydrogel promotes wound healing in a murine model of Pseudomonas aeruginosa burn infection

Burn injuries are the fourth most prevalent devastating form of trauma worldwide. Among the most extensively explored materials, composite dressings with alginate loaded with herbal extract can be mentioned. This research aimed to develop a sodium alginate (SA)-based hydrogel encapsulated with Mentha aquatica (MA) methanol extract and investigate its therapeutic efficacy in the infected burn mouse model. SEM, FTIR, in vitro extract release, HPLC, mechanical test, contact angle, swelling, degradability, and temperature response properties were used to analyze the hydrogel scaffold's physicochemical structure. Additionally, the antibacterial activity and MIC level of the extract, cell cytotoxicity, and macroscopic and microscopic analysis of the wound healing process were done using Masson's trichrome and hematoxylin-eosin staining. The physicochemical properties of the SA hydrogel encapsulated with MA extract were verified. The lowest inhibitory dose of the extract was determined to be 12.5 mg/ml. Application of SA/MA hydrogel to localized wounds of deep third-degree burns demonstrated faster tissue regeneration, collagen recovery, and eradication of bacterial infection. This research focused on the design and the preparation of a novel and effective biomaterials-based medical product, which has the potential to rehabilitate infected and injured skin tissue; therefore, it can be a promising candidate for wound dressing applications.