Wound Area Research Articles

Injective hydrogel loaded with liposomes-encapsulated MY-1 promotes wound healing and increases tensile strength by accelerating fibroblast migration via the PI3K/AKT-Rac1 signaling pathway

Failed skin wound healing, through delayed wound healing or wound dehiscence, is a global public health issue that imposes significant burdens on individuals and society. Although the application of growth factor is an effective method to improve the pace and quality of wound healing, the clinically approved factors are limited. Parathyroid hormone (PTH) demonstrates promising results in wound healing by promoting collagen deposition and cell migration, but its application is limited by potentially inhibitory effects when administered continuously and locally. Through partially replacing and repeating the amino acid domains of PTH(1–34), we previously designed a novel PTH analog, PTH(3–34)(29–34) or MY-1, and found that it avoided the inhibitory effects of PTH while retaining its positive functions. To evaluate its role in wound healing, MY-1 was encapsulated in liposomes and incorporated into the methacryloyl gelatin (GelMA) hydrogel, through which an injectable nanocomposite hydrogel (GelMA–MY@Lipo, or GML) was developed. In vitro studies revealed that the GML had similar properties in terms of the appearance, microstructure, functional groups, swelling, and degradation capacities as the GelMA hydrogel. In vitro drug release testing showed a relatively more sustainable release of MY-1, which was still detectable in vivo 9 days post-application. When the GML was topically applied to the wound areas of rat models, wound closure as well as tensile strength were improved. Further studies showed that the effects of GML on wound repair and tensile strength were closely related to the promotion of fibroblast migration to the wound area through the controlled release of MY-1. Mechanically, MY-1 enhanced fibroblast migration by activating PI3K/AKT signaling and its downstream molecule, Rac1, by which it increased fibroblast aggregation in the early stage and resulting in denser collagen deposition at a later time. Overall, these findings demonstrated that the nanocomposite hydrogel system promoted skin wound healing and increased tensile strength, thus offering new potential in the treatment of wound healing.

Integrated In Vivo and In Vitro Evaluation of a Powder-to-Hydrogel, Film-Forming Polymer Complex Base with Tissue-Protective and Microbiome-Supportive Properties.

The study aimed to perform a comprehensive in vitro and in vivo evaluation of a newly developed, patent-pending, powder-to-hydrogel, film-forming polymer complex base, which possesses tissue-protective and microbiome-supportive properties, and to compare its characteristics with poloxamer 407. The study used a combination of in vitro assays, including tissue viability and cell migration, and in vivo wound healing evaluations in male diabetic mice. Microbiome dynamics at wound sites were also analyzed. The in vitro assays demonstrated that the polymer complex base was non-cytotoxic and that it enhanced cell migration over poloxamer 407. In vivo, the polymer complex base demonstrated superior wound healing capabilities, particularly in combination with misoprostol and phenytoin, as evidenced by the reduced wound area and inflammation scores. Microbiome analysis revealed favorable shifts in bacterial populations associated with the polymer complex base-treated wounds. The polymer complex base demonstrates clinical significance in wound care, potentially offering improved healing, safety and microbiome support. Its transformative properties and efficacy in drug delivery make it a promising candidate for advanced wound care applications, particularly in chronic wound management.

Human Breast Milk Enhances Cellular Proliferation in Cornea Wound Healing

Purpose Corneal epithelial defects from trauma or surgery heal as new epithelial cells grow centripetally from the limbus and replenish the epithelium. Corneal wound healing requires cell signalling molecules. However, a topical treatment with these components is not available. Human breast milk (HBM) offers a potential, novel treatment as it contains bioactive molecules important in epithelial cell healing. This study seeks to investigate the potential of HBM in cornea wound healing. Methods Balb/c mice, 8–12 weeks old, were anesthetized prior to creating a 2 mm central cornea epithelial defect. Mice were randomly assigned to a treatment group: HBM, ophthalmic ointment containing neomycin, polymyxin B, dexamethasone (RxTx), or saline and treated 4x/day for 2 days. Wound area was quantified by fluorescein and ImageJ at 0, 8, 24, and 48 h post wounding and eyes used for histology, RT-qPCR, and ELISA. Results Wounded corneas treated with HBM demonstrated increased re-epithelialization at 8 h post injury compared to saline treatments. ELISA showed significantly higher Ki67 in HBM treated eyes vs. saline control at 8 h (p = 0.0278). Additionally, immunohistology revealed more Ki67 positive cells in the HBM group compared to saline at 8 h and 24 h (p = 0.0063 8 h; p = 0.0007 24 h). For inflammatory analysis, HBM group IL-1β levels were similar to the saline group, and higher than RxTx treated eyes (p < 0.05). Immunohistochemical staining for CD11b (macrophage marker) revealed HBM-treated eyes had significantly more positive cells vs. saline. RT-qPCR of limbal stem cell markers (LESCs) revealed upregulation of Integrin αV at 8 h with HBM vs. saline. Conclusions HBM treatment on corneas with debridement of epithelium demonstrated improved healing, cellular proliferation, and upregulation of the LESC gene transcript, integrin αV, after wounding. Future studies could investigate LESC response to different signalling molecules in HBM to better understand the efficacy of this potential therapy.

Indole-3-carbinol loaded-nanocapsules modulated inflammatory and oxidative damages and increase skin wound healing in rats

This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.

Efficacy of autologous platelet-rich plasma gel in patients with hard-to-heal diabetic foot ulcers: a multicentre study in Japan.

To evaluate the healing outcome of a platelet-rich plasma (PRP) gel prepared using TKKT01 (a wound care device to prepare the PRP gel) in patients with hard-to-heal diabetic foot ulcers (DFUs) and who showed an inadequate response to ≥4 weeks of standard of care (SoC). This open-label, single-arm, multicentre study was conducted in 15 centres in Japan. Eligible patients received PRP gel treatment twice a week for eight weeks, followed by a final evaluation after the completion of week 8 (day 57). The primary endpoint was the percentage of patients who achieved ≥50% reduction in wound radius at the final evaluation (achievement criterion, ≥60% of patients). Secondary endpoints included: wound area and volume reduction rates; time to possible wound closure by secondary intention; time to possible wound closure using a relatively simple procedure (e.g., skin graft and suture); and safety at the final evaluation. A total of 54 patients were included in the full analysis set, with 47 patients included in the per protocol set; the primary endpoint was met in 38/47 (80.9%) (95% confidence interval: 66.7-90.9%) patients who achieved ≥50% wound radius reduction at the final evaluation. High rates of wound area (72.8%) and volume (92.7%) reduction were observed at the final evaluation. The median time to possible wound closure by secondary intention and by use of a relatively simple procedure was 57 and 43 days, respectively. Complete wound closure at the final evaluation was achieved in 27 (57.4%) patients. No safety concerns were raised. In this study, the efficacy and safety of PRP gel treatment with TKKT01 in patients with hard-to-heal DFUs in Japan were confirmed by our findings. This study was funded by Rohto Pharmaceutical Co., Ltd., Japan. NO has been paid a consulting fee by Rohto Pharmaceutical Co., Ltd. KH is the Chief Medical Officer of Rohto Pharmaceutical. Co., Ltd. The other authors have no conflict of interest to declare.

Effectiveness and safety of an innovative silicone extender in suture reinforcement or dermatotraction: a retrospective study.

Multiple techniques are available for closing skin defects, such as skin grafts, flaps and tissue expansion. The tissue extender MID SEW (MID, France) was developed to achieve dermatotraction or suture reinforcement. The aim of this study was to evaluate the effectiveness and safety of this innovative silicone extender for large surgical wounds. A single-centre retrospective and observational study on an unselected consecutive cohort of patients treated with a tissue extender was conducted. Indications, initial and final wound surfaces, and adverse events (AEs) were retrieved from electronic medical records. The main outcome measure was the time to complete wound closure. We identified 50 patients from July 2017 to December 2018. Patients underwent cutaneous tumour-wide excision (n=44), or pilonidal disease surgical treatment (n=6). The average initial wound area was 53.3±42.4cm2. Healing was complete, without secondary dehiscence, within the first seven days after device withdrawal for 41 patients (82%). At least one AE was experienced by eight patients (16%) during the study period: five inflammation; five wound dehiscence; two skin necrosis; and one pain. This case series suggests that the tissue extender may be effective and safe in its dermatotraction and suture reinforcement indications in the treatment of large wounds after wide excision of skin cancer or treatment of pilonidal disease. This work was supported in part by the Hospices Civils de Lyon, France and in part by the University Claude Bernard Lyon 1, France. OB co-owns the patent on the MID SEW system. The authors have no other conflicts of interest to declare.

Comparative Analysis of Mathematical Models and App-Based Measurement for Estimating the Cutaneous Wound Areas of Captive Asian Elephants.

Objective To evaluate the variation in the area estimation under different mathematical calculations against measurement by a smartphone application in estimating the cutaneous wound areas in captive Asian elephants. Methods The study was conducted on captive Asian elephants (Elephas maximus) with cutaneous wounds reported to Veterinary Hospitals of Kerala Veterinary and Animal Sciences University and elephant camps within and outside Kerala state (mostly southern states of India, namely, Kerala and Tamil Nadu) over the period September 2019 to October 2022. Thirty-five clinical cases diagnosed with skin wounds of different aetiologies at various parts of the body were subjected to measurement, and 111 measurements were taken using a smartphone application, Imito Measure (Imito AG, Zurich, Switzerland). Based on the outer wound perimeters hand-marked on the mobile screen over the image taken, Imito Measure calculated the length, width, perimeter, and area. The length and width measurements from this were applied to four mathematical models of wound measurements. Wound surface area calculations were further done by these models and were compared. Results The observed results indicated no significant difference between the five methods of area measurement in all the studied cases since the P > 0.05. Conclusion The findings revealed no significant difference between the five techniques of wound area measurement. From the practical clinical utility point, the smartphone application has an edge over the mathematical methods in animals, especially captive Asian elephants, as it has the major advantage of being non-contact and thus addresses some major welfare concerns.

Dehydrated Amnion Chorion Membrane versus standard of care for diabetic foot ulcers: a randomised controlled trial.

Diabetic foot ulcers (DFUs) continue to challenge wound care practitioners. This prospective, multicentre, randomised controlled trial (RCT) evaluated the effectiveness of a dehydrated Amnion Chorion Membrane (dACM) (Organogenesis Inc., US) versus standard of care (SoC) alone in complex DFUs in a challenging patient population. Subjects with a DFU extending into dermis, subcutaneous tissue, tendon, capsule, bone or joint were enrolled in a 12-week trial. They were allocated equally to two treatment groups: dACM (plus SoC); or SoC alone. The primary endpoint was frequency of wound closure determined by a Cox analysis that adjusted for duration and wound area. Kaplan-Meier analysis was used to determine median time to complete wound closure (CWC). The cohort comprised 218 patients, and these were split equally between the two treatment groups with 109 patients in each. A Cox analysis showed that the estimated frequency of wound closure for the dACM plus SoC group was statistically superior to the SoC alone group at week 4 (12% versus 8%), week 6 (22% versus 11%), week 8 (31% versus 21%), week 10 (42% versus 27%) and week 12 (50% versus 35%), respectively (p=0.04). The computed hazard ratio (1.48 (confidence interval: 0.95, 2.29) showed a 48% greater probability of wound closure in favour of the dACM group. Median time to wound closure for dACM-treated ulcers was 84 days compared to 'not achieved' in the SoC-treated group (i.e., ≥50% of SoC-treated DFUs failed to heal by week 12; p=0.04). In an adequately powered DFU RCT, dACM increased the frequency, decreased the median time, and improved the probability of CWC when compared with SoC alone. dACM demonstrated beneficial effects in DFUs in a complex patient population. This study was funded by Organogenesis Inc., US. JC serves as a consultant and speaker for Organogenesis. RDD serves as a speaker for Organogenesis. OMA and MLS serve as consultants for Organogenesis. The authors have no other conflicts of interest to declare.

Potensi Tanaman Ganjan (Artemisia vulgaris) dalam Penyembuhan Luka Sayat pada Tikus (Sprague Dawley)

Recent studies have focused on exploring natural remedies to accelerate wound healing. One such herbal plant is the Ganjan plant (Artemisia vulgaris), which contains essential oils, coumarins, flavonoids, triterpenoids, and phenolic acids, which make it a good candidate for natural remedies. This study analyzed the wound-healing potential of the Ganjan plant using a true experimental research design on 16 male Sprague Dawley rats. The rats were divided into four groups and subjected to different treatments, including a negative control group without treatment (K1), a 10% Ganjan herbal extract ointment group (K2), a 30% Ganjan herbal extract ointment group (K3), and a positive control group with 10% betadine ointment (K4). The ointments were applied once daily for 21 days or until the wounds healed, and wound area measurements were taken every three days. The results showed that the 10% and 30% Ganjan ointments effectively reduced the wound area, and there was no difference in wound contraction between 10% and 30% Ganjan ointment and 10% Betadine. The study concludes that Ganjan plant extract ointment is an effective natural remedy for wound healing and that the best results are seen in the 30% Ganjan extract ointment group.

EFFECTIVENESS OF AUTOLOGOUS PLATELET-RICH PLASMA FOR HEALING DIABETIC FOOT ULCERS

Autologous platelet-rich plasma (APRP) is widely used to accelerate the healing of chronic wounds. However, the advisability of its use in patients with diabetic foot ulcers (DFU), which develop in various forms of the disease and are associated with complex metabolic conditions, is still being discussed. This study consisted in a comparative analysis of the effectiveness of local use of autologous platelet-rich plasma in the treatment of DFU in patients with neuropathic and neuroischemic forms of the disease. A total of 106 patients with type 2 diabetes mellitus undergoing hospital treatment were divided into a study group (n=48) and a traditional wound therapy group (n=58), similar in ankle-brachial index values ​​and ulcer size. Systemic therapy in both groups of patients included measures to regulate metabolism and nutrition, and infection control. Treatment results were assessed by the area of foot wounds and duration of healing. The duration of therapy and the mean platelet concentration in autologous plasma did not differ between groups. The wound healing time in patients with the neuropathic form (60.4±23.77 days) and the neuroischemic form of the disease (64.8±29.6 days) during treatment with APRP was significantly shorter than in the subgroups of the comparison group with traditional treatment of DFU (85.11±40.7 and 90.40±47.12 days respectively) (p&lt;0.01), but there was no significant difference between the subgroups receiving treatment with APRP. Although there was no significant difference in the average daily healing area among all subgroups (p&gt;0.05), the rate of wound healing in the subgroups with APRP was higher (14.85±10.66 and 15.33±14.91 mm2/day, respectively) than in the subgroups of the comparison group (8.39±6.02 and 8.79±7.13 mm2/day, respectively), which confirms the effectiveness of local treatment with APRP in combination with traditional systemic therapy.

The efficacy of topical oxygen therapy for wound healing: A meta-analysis of randomized controlled trials and observational studies.

In preclinical studies, topical oxygen treatment (TOT) was shown to enhance wound healing by applying supplemental oxygen topically to the surface of a moist wound at normobaric conditions. The objective of this systematic review and meta-analysis is to provide a thorough evaluation of published RCTs and observational studies that compare supplemental TOT with standard wound care. A total of 1077 studies were obtained from a variety of databases, including PubMed, ScienceDirect, Web of Science, ProQuest, Scopus, ClinicalTrials.gov, EU Clinical Trial Registers, and Preprints.org. The Jadad scale was employed to assess the reliability of RCT studies, while the Newcastle-Ottawa Scale (NOS) was employed to assess the quality of observational studies. Seven RCT studies (n = 692) and two controlled observational studies (n = 111) were analysed. The rate of healed wounds was 25.8% in the control group and 43.25% in the adjuvant TOT group, which shows the use of TOT significantly increased the number of healed wounds (RR = 1.77; 95% CI 1.18-2.64; p = 0.005). A significant decrease in the percentage of wound area was found in the TOT group in RCT studies (mean difference = 15.64; 95% CI 5.22-26.06; p = 0.003). In observational studies, the rate of healed wounds was 37.5% in the standard care group and 80.95% in the adjuvant TOT group, which shows a significant increase in the number of healed wounds in the adjuvant TOT group (RR = 2.15; 95% CI 1.46-3.15; p < 0.00001). Topical oxygen therapy is considered a great adjuvant therapy for chronic wound healing, particularly wounds with vascular compromise such as diabetic ulcers and pressure ulcers. Further studies on this topic are still needed as there are a lot of potential uses for this technology in various types of wounds.

Evaluation of nanocellulose-based anthraquinone from marine fungi Penicillium flavidorsum as an alternative therapy for skin wound healing: histopathological and immunohistochemical evidences from a rat model

BackgroundWound healing represents a complex clinical challenge, necessitating the selection of appropriate wound dressings to facilitate an efficient healing process. This study aims to explore an effective approach to enhance wound healing by investigating the therapeutic potential of a nanocellulose-based anthraquinone derived from marine fungi.Forty male Wistar rats were divided into five groups, including a control group and various four treatment groups. The wound healing process was assessed by measuring the wound area at different time points.ResultsThe results showed promising outcomes in terms of wound healing progression. The group treated with anthraquinone and nanocellulose demonstrated the most favorable results, with normal epidermal architecture, marked hyperkeratosis, and minimal dermal edema. This study provides comprehensive evidence supporting the efficacy of this novel alternative therapy through histopathological and immunohistochemical analyses conducted on a rat model.ConclusionBy addressing the limitations associated with conventional wound dressings, our research contributes to the development of innovative strategies for optimizing wound healing outcomes. The findings presented herein underscore the potential of nanocellulose-based anthraquinone as a promising therapeutic option for promoting skin wound healing. Further investigations are warranted to elucidate the underlying mechanisms and establish the clinical viability of this alternative therapy.

Relationship between gene expression associated with cellular senescence in cells from discarded wound dressings and wound healing: A retrospective cohort study

AimSenescent cells, inducing a senescence-associated secretory phenotype (SASP), lead to chronic inflammation in hard-to-heal wound tissue. However, eliminating senescent cells may impede normal wound healing due to their important role in the wound healing mechanism. Accordingly, we focused on wound exudates in hard-to-heal wounds, which contain many inflammation biomarkers consistent with SASP. Therefore, we hypothesized that senescent cells might be present in the exudates and induce chronic inflammation. This study investigated the relationship between gene expression associated with cellular senescence in exudates from pressure injuries and wound healing status. MethodsThis retrospective cohort study involved patients treated by a pressure injury team. We collected viable cells from wound dressings and analyzed gene expression. Pearson's correlation coefficient was calculated between cellular senescence and SASP expression. The relationship between the gene expression of cellular senescence and the wound area reduction rate by the following week was examined using a mixed-effects model. ResultsCDKN1A—related to cellular senescence—was expressed in 96.3 % of 54 samples, and CDKN1A expression and SASPs positively correlated (PLAU: r = 0.68 and TNF: r = 0.34). Low CDKN1A expression was statistically associated with a large wound area reduction rate (β = 0.83, p < 0.01). ConclusionsGene expression of both cellular senescence and SASP factor in wound dressings suggests the presence of cellular senescence. Senescent cells in wound dressings could be associated with delayed wound healing in the following week.

Comparison between Ketogenic and Diabetic Conventional Diet on Wound Closure in Diabetic Rat Model

Background: Managing diabetic ulcers should be multimodal; nutrition is one of the modalities to improve wound healing. This study therefore aimed to compare ketogenic diet and conventional diabetic diet in closing the wounds of diabetic rat models.Methods: Diabetes mellitus was induced in 30 rats which were divided equally into three groups. Group I was given a ketogenic diet (60% fat, 24% carbohydrate, and 16% protein). Group II was given a conventional diabetic diet (43% carbohydrate, 15% fat, and 42% protein). Group III was the control group with a normal diet (13% water, 18.5%–20.5% protein, fat ≥4%, fiber ≤6%, ash ≤8%, 0.9% calcium, and 0.7% phosphor). A 1 cm-diameter wound was made with the Mason-Walker model as a guideline. The rate of wound closure was measured on days 1, 7, 14, and 21 to represent each wound healing phase.Results: On day 7, comparison between wound areas in the ketogenic diet, conventional diet, and normal diet yielded significant differences (mean, 0.664, 0.717, 0.747; P=0.051). There was also a significant difference on day 14 (mean, 0.564, 0.817, 0.647; P&lt;0.001) and day 21 (mean, 0.164, 0.517, 0.447; P&lt;0.001).Conclusion: Compared to a conventional diabetic diet, a ketogenic diet significantly enhanced the wound closure rate in the diabetic rat model. Further studies are needed to confirm this finding.

Chlorogenic Acid: HPLC Quantification and In Vitro Assessment of Proliferative and Migration Effects on Human Dermal Fibroblast Cells

Chlorogenic acid (CA) exhibits diverse biological activities, including antioxidant and antiinflammatory effects. This research aims to develop, optimize, and validate an HPLC method to quantify CA in methanol and investigate its in vitro proliferative and cell migration effects on human-dermal-fibroblast (HDF) cell lines in a dose-dependent manner. The HPLC experimental conditions were optimized using the central composite design (CCD) method for determining CA. Chromatographic separation occurred at a wavelength of 330 nm. Under the optimized conditions, the method exhibited linearity across a concentration range of 0.1-100 µg/mL, demonstrating sensitivity (LOQ:0.1µg/mL), precision (RSD%≤3.32), and accuracy (RE%≤4.05). To evaluate the in vitro proliferative and cell migration effects on HDFs, we employed the XTT cell proliferation assay and TAS-TOS commercial kits. The XTT assay revealed that CA displayed a proliferative effect within the concentration range of 75-250 µM (P &amp;lt;0.01), and at a concentration of 125 µM, TAS levels increased significantly (P&amp;lt;0.05). The scratch assay demonstrated that HDF cell migration increased at 12 h, with substantial closure of the wound area at 24 h when treated with CA concentrations between 75-125 µM. The results demonstrate that pure chlorogenic acid extracted from plants exhibits dose-dependent effects on cell proliferation, antioxidant, and cell migration

Hydroxyproline as a Marker of the Efficiency of Skin Wound Therapy in Ischemic Conditions

The aim of the study was to analyze the level of hydroxysoplin in tissues as a marker of healing efficiency of experimental skin wound under ischemia conditions. A wound was reproduced according to our developed method on 90 rats Vistar. There were 3 groups of rats of 30 individuals. Therapy was not carried out in the group «Control», local treatment with multi-component means was performed in the «First experimental» group, magnetotherapy was performed with the above-mentioned agent in the «Second experimental» group. The hydroxylol content was estimated based on Newman’s, Logan’s technique modified by Cissel. The results were compared with planimetric, visual and morphological data. The formation of scar was observed in each series on the 10th day, there was recorded the predominance of mature connective tissue over granulation in the experimental groups in contrast to the «Control» group. There was a strong correlation between the hydroxyprolin content and the wound area in all groups. The article marked the reliability of the method of quantitative analysis of hydroxyproline, which made it possible to increase the objectivity of the representation of the course of the wound process in conjunction with other methods of research.

Long duration sodium hyaluronate hydrogel with dual functions of both growth prompting and acid-triggered antibacterial activity for bacteria-infected wound healing

Conventional wound dressings are monolithically designed to cover the injured areas as well as absorb the exudates at injured site. Furthermore, antibacterial drugs and growth prompting factors are additionally appended to realize sensible and omnibearing wound management, exhibiting long and tedious treatment process in practice. Consequently, the creation of multifunctional wound dressings that combines wound repair enhancement with antibacterial properties turns out to be significant for simplifying wound managements. In our investigation, electronegative human epidermal growth factor (hEGF) was combined with the positively charged Zn-Al layered double hydroxides (Zn-Al LDHs) via electrostatic interaction while the obtained hEGF/LDH was integrated with sodium hyaluronate hydrogel (SH) hydrogel, forming a composite hydrogel with synergistic benefits for wound management. The innovative hEGF/LDH@SH hydrogel equipped with fine biocompatibility was designed to optimize wound healing in which hEGF stimulates epithelial cell growth while LDH released antibacterial factor Zn2+ against Methicillin-resistant staphylococcus aureus (MRSA) and Escherichia coli (E.coli) under acidic wound environment. Additionally, the SH hydrogel constructed a three-dimensional structure that not only safeguarded the wound area but also maintained a moist environment conducive to recovery. The synthesized hEGF/LDH was confirmed via fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and thermo-gravimetry (TG) measurements. The release of Zn2+ from Zn-Al LDH under acid circumstance was detected via inductively coupled plasma (ICP) and the in vitro bactericidal experiments endowed the antibacterial property of hEGF/LDH@SH hydrogel. In vitro drug release experiments illustrated the controlled-release of hEGF from hEGF/LDH which promoted the long-term affect of hEGF at wound site. In vitro cell experiments verified that the hEGF/LDH@SH hydrogel motivated the promotion on cell proliferation and migration without cytotoxicity. An in vivo study of the repairing of MRSA-infected wound in mice indicated that hEGF/LDH@SH hydrogel serves as a simple and novel, innoxious and efficient wound healing approach. This brand new hydrogel possesses properties of promoting the regeneration of skin tissue, achieving antimicrobial therapy without any accessional antibacterial drugs as well as realizing controlled release of hEGF.

An automated in vitro wound healing microscopy image analysis approach utilizing U-net-based deep learning methodology

BackgroundThe assessment of in vitro wound healing images is critical for determining the efficacy of the therapy-of-interest that may influence the wound healing process. Existing methods suffer significant limitations, such as user dependency, time-consuming nature, and lack of sensitivity, thus paving the way for automated analysis approaches.MethodsHereby, three structurally different variations of U-net architectures based on convolutional neural networks (CNN) were implemented for the segmentation of in vitro wound healing microscopy images. The developed models were fed using two independent datasets after applying a novel augmentation method aimed at the more sensitive analysis of edges after the preprocessing. Then, predicted masks were utilized for the accurate calculation of wound areas. Eventually, the therapy efficacy-indicator wound areas were thoroughly compared with current well-known tools such as ImageJ and TScratch.ResultsThe average dice similarity coefficient (DSC) scores were obtained as 0.958∼\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sim$$\\end{document}0.968 for U-net-based deep learning models. The averaged absolute percentage errors (PE) of predicted wound areas to ground truth were 6.41%, 3.70%, and 3.73%, respectively for U-net, U-net++, and Attention U-net, while ImageJ and TScratch had considerable averaged error rates of 22.59% and 33.88%, respectively.ConclusionsComparative analyses revealed that the developed models outperformed the conventional approaches in terms of analysis time and segmentation sensitivity. The developed models also hold great promise for the prediction of the in vitro wound area, regardless of the therapy-of-interest, cell line, magnification of the microscope, or other application-dependent parameters.

Minimization of wire-wound pressure vessel diameter based on distortion energy theory

This paper investigates the minimization of the diameter of wire-wound pressure vessels. The study is conducted in two stages. Firstly, the stresses arising from the wire winding of the vessel and the internal pressure application are extracted based on the distortion energy theory. It is assumed that the equivalent stress within the winding area in each layer, under the internal pressure condition, equals the allowable stress of the wire, and in the cylinder area, it does not exceed the allowable stress of the cylinder. The required number of layers and the wire tension during winding (two essential unknown parameters in the industrial winding process) are determined to satisfy these assumptions. In the second stage, the diameter optimization of the vessel is studied using the Distortion Energy (DE) theory. It is found that reducing the cylinder diameter results in a decrease in the vessel diameter. The occurrence of buckling or yielding in the cylinder is a limiting constraint for reducing the cylinder diameter. For validation, the results obtained from the derived equations are compared and confirmed against finite element results and the equations provided in the ASME code. Wire-winding simulation around the cylinder uses the element birth and death technique. The agreement between the derived equations and the code equations, as well as finite element results, is excellent. In the examined case study, using the DE theory leads to a 24 % reduction in wire consumption compared to the maximum shear stress (MSS) theory. In the optimization stage, the vessel weight is further reduced by 24 %. Compared to monobloc shells, the optimized wire-wound vessel weight based on the DE theory experiences a 77 % reduction.

Comparing collagenase and silver sulfadiazine in deep second-degree burn treatment.

The indications for collagenase ointment (CO) and its efficacy are not clearly established in the treatment of second-degree burn wounds. To evaluate the efficacy of CO versus silver sulfadiazine ointment (SSD) in the treatment of second-degree burn wounds. A total of 170 eligible patients with deep second-degree burns, aged 18-65 years, with injuries occurring within 48-96h, and having a total wound area of less than 30% of the total body surface area were included from 5 centers in China. The primary outcome was the wound healing time, and the secondary outcomes were the clearance time of wound necrotic tissues, wound healing rate, and wound inflammation. The study included 85 patients in SSD group and 84 in CO group in the modified intention-to-treat (mITT) population. The median time of wound healing was comparable in both groups (10 days vs. 10.5 days P = 0.16). The time for wound necrotic tissue removal was significantly shortened by CO compared with SSD (5 vs. 10 days P < 0.01). Wound inflammation, pain, wound healing rate, and scar were compared with SSD (all P-values > 0.05). No adverse events, such as infection or allergic reactions to the drugs and materials used, were reported. Both CO and SSD could heal the burn wounds at 10 days of treatment. However, CO significantly shortened the time of wound necrotic tissue removal by 5 days. Trial Registration: ChiCTR2100046971.