Skin Wound Healing Research Articles

Native and cationic cellulose nanofibril films enriched with avocado seed compounds as a green alternative for potential wound care applications

Cellulose nanofibrils (CNF) show great potential for skin wound care and healing due to their biocompatibility, non-cytotoxicity, and high swelling with good mechanical stability. In the presented study, for the first time native and cationized cellulose nanofibrils were used in combination with avocado seeds extracts obtained with different extraction methods (ASE), as an alternative to a well-known antibiotic, Clindamycin, to produce films with high and long-lasting antimicrobial efficacy. The swelling capacity of prepared films and extracts/antibiotic release kinetics were studied at different pH values to evaluate pH response behavior.All developed films exhibited high bacteriostatic and bactericidal activity against Gram-negative Escherichia coli and G-positive Staphylococcus aureus, resulting in up to 100 % bacterial reduction with the log reduction factor up to 5.64 or 6.50, at 14.2 mg of avocado seed extract or clindamycin integrated in the 1 cm2 of CNF film. The high swelling capacity (up to 65.67 %) and stability of avocado seed extracts-enriched CNF films provide a suitable moisture environment and a sustainable release (up to 40.98 % in 48 h) of bioactive compounds. The prepared antibacterial films' chemical and morphological characteristics and pH-responsive behavior proved the potential applications in the cosmetics, biomedicine, and pharmaceutical industry.

Wound Healing in External Rhinoplasty-The Effect of Fibrin Glue on Dead Space Closure: A Retrospective Propensity Score-Matched Study.

The presence of "dead space" in external rhinoplasty creates a welcoming environment for erratic soft tissue contraction. Poor redraping of the skin over the underlying osseocartilaginous framework at the end of the surgery may result in its creation. If surgeons can control and reliably predict skin contraction and wound healing, septorhinoplasty results would undoubtedly improve. Fibrin glue application has previously demonstrated a reduction in adverse events in plastic surgery. Several potential advantages have been attributed to the application of fibrin glue, such as reducing downtime, improving patient satisfaction and reducing complication rates. To evaluate the effectiveness of homologous fibrin glue on the long-term healing process in external rhinoplasty. We performed a retrospective propensity score-matched analysis in 154 patients enrolled for external septorhinoplasty. An aesthetic evaluation was performed with the FACE-Q nose and nostrils, the Utrecht Questionnaire including VAS score and the NOSE. Assessments were conducted prior to surgery and post-operatively at 3, 6 and 12months. After propensity score matching, two equal groups of 66 patients were retained. The first cohort of 66 patients underwent a rhinoplasty without the application of fibrin glue; in the second cohort of 66 patients, human fibrin glue was used to achieve better adherence of the skin to the underlying skeletal framework. All patients had a statistically highly significant improvement on all PROMs post-operatively. The post-operative results remained stable over the different time points. However, no statistically significant difference in the aesthetic outcome was discovered whether fibrin glue was used or not during surgery. Obliteration of dead space is a key component in septorhinoplasty as it minimizes soft tissue contraction, resulting in a more predictable outcome. Although fibrin glue has been used successfully in different medical fields, no long-term positive effects on patient satisfaction could be detected in the present study. 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 .

Nanodrug-Engineered Exosomes Achieve a Jointly Dual-Pathway Inhibition on Cuproptosis.

Cuproptosis, caused by an intracellular overload of copper (Cu) ions and overexpression of ferredoxin 1 (FDX1), is identified for its regulatory role in the skin wound healing process. This study verifies the presence of cuproptosis in skin wound beds and reactive oxygen species-induced cells model. To address the two pathways leading to cell cuproptosis, a nanodrug-engineered exosomes is proposed. A Cu-chelator (Clioquinol, CQ) polydopamine (PDA)-modified stem cell exosome loaded with siRNA-FDX1, named EXOsiFDX1-PDA@CQ, is designed to efficiently inhibit the two cuproptosis pathways. The functionalized exosomes are loaded into an injectable hydrogel and applied to treat diabetic wounds in mice and acute skin wounds in pigs. The local and controlled release of EXOsiFDX1-PDA@CQ ensures the retention of the therapeutic agent at wound beds, effectively promoting wound healing. The strategy of engineered exosomes with functional nanoparticles (NPs) proposed in this study offers an efficient and scalable new approach for regulating cuproptosis.

SCALES FOR ASSESSMENT OF SKIN SCARS. CLINICAL SIGNIFICANCE. SYSTEMATIC REVIEW.

Having a skin scar is a serious psychosocial problem for a person. Scar and cicatrices are synonymous concepts. Interpretation of scar characteristics is necessary for monitoring purposes and, if necessary, determining treatment tactics. Subjective characteristics of the scar (pain, itching, etc.) are very important for the formation of a comprehensive assessment. Healing of skin wounds can lead to the formation of different types of scars: from minor lines to keloids. The physical and psychosocial aspects of having a skin scar can lead to a decrease in the patient's quality of life. Today, the question remains controversial which criteria for assessing a scar should be included in a particular tool (scale) for its comprehensive assessment. The ideal scar rating scale should not be difficult to complete, and the measurement results are easily reproducible and interpretable. It is important to determine the impact of the scar on psychosocial parameters (quality of life, self-esteem, social function of the patient). This literature review included 19 full-text articles containing information on ten developed skin scar rating scales. The literature review was carried out based on a search in the PubMed, Web of Science, Google Scholar and Elibrary.

Adipose-mesenchymal stem cell-derived extracellular vesicles enhance angiogenesis and skin wound healing via bFGF-mediated VEGF expression.

This study aimed to investigate whether extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ASCs) promote skin wound healing by delivering basic fibroblast growth factor (bFGF) to enhance vascular endothelial growth factor (VEGF) expression. ASCs were isolated and transfected with either a bFGF knockdown lentivirus (Lv-sh-bFGF) or a control lentivirus (Lv-sh-NC). EVs were extracted from ASCs cultures and characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting for surface markers. EVs were extracted from the conditioned mediums of ASCs and subjected to different treatments. These EVs or control treatments were injected at the wound edges. Wound healing was assessed using histological techniques, including H&E and Masson's trichrome staining to evaluate tissue regeneration, collagen organization, and immunohistochemistry for CD31 to quantify microvessel density. Protein expression of bFGF and VEGF was measured by Western blotting. ASC-derived EVs significantly promoted angiogenesis and improved skin wound healing. EVs encapsulating bFGF enhanced VEGF expression in the wound tissue, while knockdown of bFGF reduced both bFGF and VEGF expression, leading to delayed wound healing. Further knockdown of VEGF partially reversed the pro-angiogenic and wound-healing effects of bFGF-encapsulated EVs. This study demonstrates that ASC-derived EVs promoted skin wound repair by enhancing angiogenesis and accelerating tissue regeneration through the bFGF/VEGF axis. These findings highlight the therapeutic potential of ASCs-derived EVs in improving skin wound healing.

A continuous mode of action of nitric oxide in hard-to-heal wound healing.

Nitric oxide (NO) is one of the most studied molecules in medical science. The role of NO as an endogenous regulator of inflammation, as an antibacterial agent and as an endogenous gasotransmitter is well established. Even so, despite a plethora of excellent wound healing data, hard-to-heal (chronic) wounds are of epidemic proportions, and still growing in number. However, yet to be established and sorely needed is the identification of a single, continuous NO mechanism of action (MoA), where phase-to-phase variance in the complex sequence of cellular and molecular wound healing may elucidate the potential for placing hard-to-heal wounds on positive healing trajectories. Hence, the objectives of this review were to: identify salient MoAs for NO in each phase of skin wound healing; and to select and validate a single MoA that is both ubiquitous and continuous in NO across acute and hard-to-heal wound sequences, and which potentiates the ability to supplementally motivate and guide the recovery of a hard-to-heal wound onto a positive healing trajectory. The search began by selecting a detailed, multipart wound healing model. Next, as guided by the literature, was the identification of salient NO functionalities for each model segment. These modes of action were then be used to identify and validate a single NO MoA that is continuous across the healing spectrum. Finally, by using the principle of 'super position' of two continuous functions, this acute healing NO MoA solution was compared to a similar solution set describing a hard-to-heal or chronic wound. As both solution sets are continuous in a NO function, the resultant 'overlay' then helped to identify and guide the use of a NO MoA capable of placing any hard-to-heal wound on a positive healing trajectory.

The cyclization of human salivary Histatin 1 via click chemistry for skin wound healing

Acute skin injuries can result in the breakdown of the skin barrier, heightening the risk of infections and complications. Histatin 1 (Hst1) promotes the adhesion, spreading, and migration of various skin-related cells, thus encouraging wound healing. However, Hst1 is extensively degraded upon exposure to wound exudates. Cyclized hst1 (Cyclic-hst1) has a much higher resistance to protease degradation than Hst1, thus increasing its stability and half-life. Herein, we synthesized Cyclic-hst1 via a click reaction and explored its efficacy in wound healing via cellular and animal experiments. Cyclic-hst1, at a 100-fold lower concentration than Hst1, effectively promoted acute skin wound healing. In addition, Cyclic-hst1 had a superior effect to Hst1 in terms of its anti-inflammatory, re-epithelialization, collagen deposition, and angiogenic effects, thus significantly promoting skin wound healing. Consequently, Cyclic-hst1 could represent a favorable treatment to manage acute skin wound healing, providing a promising experimental basis for clinical transformation and application.

Double-alternating injectable multifunctional hydrogel based on chitosan for skin wound repair.

Injectable hydrogels can be suitable for any irregular wounds to play an important role in wound healing, which have attracted much attention from researchers. Here, a chitosan-based double alternating injectable hydrogel had been proposed, which aligned with characteristics of wound healing. First of all, carboxymethyl chitosan (CMCS) and oxidized gellant (OGG) were used to fabricate above double-alternating injectable hydrogel skeleton (COG) through Schiff base bond. Then, dipotassium glycyrrhizinate (DPG) and bioactive glass (BG) were loaded respectively into COG, forming COG2-D10 and COG2-B0.5 hydrogel. Various properties of above hydrogels such as rheological behaviors, injectable capability, cytocompatibility, antibacterial and anti-inflammatory activity were systematically investigated. The results indicated that above hydrogel not only had a stable network structure, good toughness, injectability, and excellent adhesive properties, but also exhibited efficient antibacterial, anti-inflammatory, hemostatic, and biocompatible properties. The investigation of in vivo full-thickness skin wound healing showed that compared with COG2-D10 or COG2-B0.5 hydrogel alone, the double-alternating COG2-D10/COG2-B0.5 hydrogel could better enhance the efficacy of drugs, promote cell migration and proliferation, accelerate collagen fiber deposition and neovascularization, and significantly improve wound healing (p < 0.01). Therefore, the double-alternating therapy strategy of hydrogel will provide a new approach for the clinical treatment of skin wound healing.

Targeted Antibacterial Endolysin to Treat Infected Wounds on 3D Full-Thickness Skin Model: XZ.700 Efficacy

Backgrounds/Objectives: Skin wound healing is a physiological process orchestrated by epithelial and mesenchymal cells able to restore tissue continuity by re-organizing themselves and the ECM. This research study aimed to develop an optimized in vitro experimental model of full-thickness skin, to address molecular and morphological modifications occurring in the re-epithelization and wound healing process. Methods: Wound healing starting events were investigated within an experimental window of 8 days at the molecular level by gene expression and immunofluorescence of key epidermal and dermal biomarkers. To mirror the behavior of infected wounds, the established wound healing model was then colonized with S. aureus, and the efficacy of a novel antibacterial agent, XZ.700, was investigated. Viable counts (CFU/tissue), IF, and ultrastructural analysis (SEM) were performed to evaluate S. aureus colonization inside and around the wound bed in an experimental window of 3 h of colonization and 24 h of treatment. Results: Endolysin showed an efficacy in counteracting bacterial growth and invasion within the wound bed, reducing the S. aureus load compared to its placebo, thanks to its selective antimicrobial activity interfering with biofilm formation. Conclusions: The preclinical in vitro infected wound model on FT-kin showed interesting applications to assess the repair efficacy of dermo-pharmaceutical and cosmetic formulations.

526 Macrophage cell death instructs fibroblast-repair functions in skin wound healing

526 Macrophage cell death instructs fibroblast-repair functions in skin wound healing

Engrailed-1 inactivation leads to scarless skin wound healing through extracellular matrix remodeling

Engrailed-1 inactivation leads to scarless skin wound healing through extracellular matrix remodeling

Licochalcone A loaded multifunctional chitosan hyaluronic acid hydrogel with antibacterial and inflammatory regulating effects to promote wound healing

The wound healing process is characterized by persistent infection and long-term inflammation. The licochalcone A (LicA) has the potential for skin wound healing and needs a good drug-loading platform to apply its antibacterial and anti-inflammatory effects. In this study, the LicA@chitosan (CS) -hyaluronic acid (HA) hydrogel with antibacterial and anti-inflammatory was developed for wound healing in mice. The SEM displayed that the hydrogel had an obvious porous structure and was very suitable to be used as a delivery carrier for LicA. The FTIR results suggested that the LicA can be effectively loaded in the CS-HA hydrogel. Variable strain scanning, frequency scanning and temperature scanning indicated that the LicA@CS-HA hydrogel can maintain the gel state. The LicA@CS-HA hydrogel had good biological safety, can inhibit the activity of Escherichia coli and Staphylococcus aureus, and can release LicA stably. The LicA@CS-HA hydrogel also has good adhesion and hemostatic properties. Finally, the LicA@CS-HA hydrogel significantly accelerated wound healing in mice skin injury model, and reduced inflammation and orderly collagen deposition were observed by HE and Masson staining. The immunohistochemistry indicated that the LicA@CS-HA hydrogel induced the positive expression of CD31, VEGF, and HIF-1α promoted neovascularization. The LicA@CS-HA hydrogel also down-regulated the expression of M1 macrophage markers CD86, IL-6, and TNF-α, and increased the expression of M2 macrophage markers CD206, IL-4, and IL-10 proteins. The molecular docking demonstrated that the target proteins had better binding activity to LicA. Collectively, the LicA@CS-HA hydrogel has broad application prospects in promoting wound healing.

Zuyangping formula promotes skin wound healing in diabetic rats.

To evaluate the effects of Zuyangping (, ZYP) formula on wound healing in diabetic rats, as well as the molecular mechanisms involved. The main compounds in ZYP formula were identified by the Liquid chromatography-tandem mass spectrometry. Sprague-Dawley rats, injected with streptozotocin (STZ) to establish diabetes model, then, formed a defective skin trauma in the back, and each group was treated with corresponding drugs once a day. Granulation was taken from each time node for histological analysis. The Western blotting was used to measured protein expression of advanced glycation end products receptor (RAGE) and hypoxia-inducible factor-1α (HIF-1α) axis-related proteins. The relative expression levels of inflammatory cytokines and growth factors were measured by the enzyme-linked immunosorbent assay method. The main ingredients were identified in the ZYP formula. Histological analysis showed that the ZYP formula could inhibit the expression of inflammation, promote angiogenesis and collagen deposition. In addition, the ZYP formula could regulate the expression of RAGE and HIF1-α axis-related proteins, thus promoting the wound healing in diabetic rats. The ZYP formula could accelerate wound healing in diabetic rats.

539 Mitochondria-encoded Circ-mtRNR2 improves the impaired skin wound healing of Diabetic Foot Ulcer by regulating fibroblast function and mitochondrial superoxide production

539 Mitochondria-encoded Circ-mtRNR2 improves the impaired skin wound healing of Diabetic Foot Ulcer by regulating fibroblast function and mitochondrial superoxide production

546 ScRNA-seq uncovers keratinocyte heterogeneity and dynamics in healthy human skin wound healing

546 ScRNA-seq uncovers keratinocyte heterogeneity and dynamics in healthy human skin wound healing

537 Full-length transcript sequencing of fibroblasts and keratinocytes reveals isoform diversity in human skin wound healing

537 Full-length transcript sequencing of fibroblasts and keratinocytes reveals isoform diversity in human skin wound healing

522 Characterisation of skin wound healing of aged Sox2EGFP mice

522 Characterisation of skin wound healing of aged Sox2EGFP mice

Construction of multifunctional hydrogel containing pH-responsive gold nanozyme for bacteria-infected wound healing

Nanozymes have become promising alternative antibacterial agents for bacteria-infected wounds. In this study, fucoidan-confined gold nanoparticles (Fuc@AuNPs) are developed by in situ reduction, and stabilized by sulfate groups of fucoidan. Fuc@AuNPs exhibit pH-responsive catalytic activity that can mimic oxidase (OXD) under acidic bacterial infection conditions and mimic superoxide dismutase (SOD) under normal physiological conditions. The OXD-like catalytic activity of Fuc@AuNPs generates active singlet oxygen (1O2), exhibiting effective antibacterial properties against both Gram-negative E. coli and Gram-positive S. aureus. Fuc@AuNPs and aldehyde grafted saponin incorporate with chitosan to form a hybrid hydrogel. This hydrogel exhibits superior mechanical, adhesive, and self-healing properties due to electrostatic complex coacervation networks and dynamic covalent Schiff base reactions. Animal experiments show that the hydrogel aids S. aureus-infected skin wound healing by reducing bacterial infection and promoting granulation tissue formation without causing excessive ROS-induced inflammation. This study presents the design of multifunctional nanozymes and bioactive hydrogels as a promising wound healing dressing for biomedical applications.

G(1-5)-EM2, a multi-targeted agonist to opioid and growth hormone secretagogue receptors exhibited nontolerance forming antinociceptive effects in a mouse model of burn pain

Burn induced-pain (BIP) is one of the most common pain symptoms, which seriously affects the quality of sufferer life. Researches show that multi-targeted drug therapies offer superior efficacy and fewer side effects compared to single-target drug therapies. Consequently, in this study, we developed G(1-5)-EM2, a multi-targeted peptide designed to target μ-opioid receptor and the growth hormone secretagogue receptor 1α (GHS-R1α), and explored its antinociceptive effects on burn injury pain. Calcium mobilization experiments revealed that G(1-5)-EM2 demonstrated weak multi-agonist activities to μ-opioid receptor and κ-opioid receptor as well as GHS-R1α in vitro. Near-infrared fluorescence imaging experiments demonstrated that G(1-5)-EM2 could penetrate the blood-brain barrier (BBB) and access the brain following intravenous injection. The enzymatic stability of G(1-5)-EM2 was significantly enhanced compared to EM2. Our results indicated that intrathecal administration of G(1-5)-EM2 mitigated mechanical allodynia and thermal hyperalgesia in BIP. These antinociceptive effects of G(1-5)-EM2 were partially mediated through μ-opioid receptor and GHS-R1α. Moreover, intrathecal administration of G(1-5)-EM2 significantly decreased burn-induced up-regulation of phosphorylated p38 MAPK, phosphorylated NF-κBp65 and TRPV1 in the ipsilateral spinal cord, reduced the levels of IL-1β, IL-6 and TNF-α in serum, and enhanced wound healing in burned skin. Repeated intrathecal administration of G(1-5)-EM2 produced a non-tolerance-forming antinociception in BIP. These results suggest that the multi-targeted peptide G(1-5)-EM2 exhibits a novel role in alleviating BIP with fewer side effects and may represent a promising strategy for developing new analgesic drugs.

Synthesis and Characterization of Inulin Polymer and Study Its Role on Wound Healing

Inulin is a particularly effective drug delivery vehicle as compared to other biodegradable polysaccharides because of its unique and flexible structure, protective and stabilizing properties, and organ targeting abilities. This strategy may result in targeted, delayed, and regulated release of medications and biomolecules as well as increased bioavailability and improved cellular absorption. In the present study, thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), 1H-NMR, and ultraviolet spectroscopy were among the techniques used to further characterize the physicochemical properties of inuline. The inulin-g-[N-sulfamethoxazole maleic amic acid] (INMS) was prepared and used. INMS efficacy against bacterial activity was also examined. In order to examine the activity of INMS in vivo, mice were underwent to second-degree burn. The results showed, after three days, the basic media produced better regulated drug release than the acidic one. This was discovered by contrasting the pace at which the amide drug polymer hydrolyzed in each media. It was discovered that a drug polymer with altered drug release and a prolonged duration of action has as an adhesive probity. The present results found that INMS has a significant antibacterial effect on burned wound isolated bacteria. The in vivo performance using a natural polymer as a drug carrier results a great healing of skin wound of mice. Thus, the present study is aimed to modify the inulin to serve as a scaffold for various drug delivery systems.