Development Of Chronic Wounds Research Articles

Neutralizing Staphylococcus aureus PAMPs that Trigger Cytokine Release from THP-1 Monocytes.

Innate immunity has considerable specificity and can discriminate between individual species of microbes. In this regard, pathogens are "seen" as dangerous to the host and elicit an inflammatory response capable of destroying the microbes. This immune discrimination is achieved by toll-like receptors on host cells recognizing pathogens, such as Staphylococcus aureus, and microbe-specific pathogen-associated molecular pattern (PAMP) molecules, such as lipoteichoic acid (LTA). PAMPs impede wound healing by lengthening the inflammatory phase of healing and contributing to the development of chronic wounds. Preventing PAMPs from triggering the release of inflammatory cytokines will counteract the dysregulation of inflammation. Here, we use ELISA to evaluate the use of cationic molecules branched polyethylenimine (BPEI), PEGylated BPEI (PEG-BPEI), and polymyxin-B to neutralize anionic LTA and lower levels of TNF-α cytokine release from human THP-1 monocytes in a concentration-dependent manner. Additional data collected with qPCR shows that BPEI and PEG-BPEI reduce the expression profile of the TNF-α gene. Similar effects are observed for the neutralization of whole-cell S. aureus bacteria. In vitro cytotoxicity data demonstrate that PEGylation lowers the toxicity of PEG-BPEI (IC50 = 2661 μm) compared to BPEI (IC50 = 853 μM) and that both compounds are orders of magnitude less toxic than the cationic antibiotic polymyxin-B (IC50 = 79 μM). Additionally, the LTA neutralization ability of polymyxin-B is less effective than BPEI or PEG-BPEI. These properties of BPEI and PEG-BPEI expand their utility beyond disabling antibiotic resistance mechanisms and disrupting S. aureus biofilms, providing additional justification for developing these agents as wound healing therapeutics. The multiple mechanisms of action for BPEI and PEG-BPEI are superior to current wound treatment strategies that have a single modality.

Chemotherapy-Mediated Complications of Wound Healing: An Understudied Side Effect.

Significance: Chemotherapy is a primary method to treat cancer. While chemotherapeutic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types. In the case of dermal cells and macrophages involved in wound healing, cytotoxicity often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent Advances: Despite its significant impact on patients' recovery from surgery, the issue of delayed wound healing in individuals undergoing chemotherapy remains inadequately explored. Critical Issues: This review aims to analyze the harmful impact of chemotherapy on wound healing. The analysis showed that chemotherapy drugs could inhibit cellular metabolism, cell division, and angiogenesis and lead to nerve damage. They impede the migration of cells into the wound and reduce the production of extracellular matrix. At the molecular level, they interfere with replication, transcription, translation, and cell signaling. This work reviews skin problems that patients may experience during and after chemotherapy and demonstrates insights into the cellular and molecular mechanisms of these pathologies. Future Directions: In the future, the problem of impaired wound healing in patients treated with chemotherapy may be addressed by cell therapies like autologous keratinocyte transplantation, which has already proved effective in this case. Epigenetic intervention to mitigate the side effects of chemotherapy is also worth considering, but epigenetic consequences of chemotherapy on skin cells are largely unknown and should be investigated.

Nano-gel formulation of polyphenolic fraction of tobacco stem for wound healing and its inhibitory efficacies against the receptors of chronic wound development

Current investigation deals with the gel formulation of purified polyphenol loaded nanoparticles for enhanced wound healing. Polyphenols purified using column chromatography an were characterized using HPLC in fractions. Silver nanoparticles were characterization using SEM, AFM, TEM, DLS. Cytotoxic effect was checked on L929 (Mouse fibroblast cells). Bioactive loaded nanoparticles were formulated in gel and subjected for physical characterization. Excision wound wistar rat models were established to measure the wound contraction measurement, histopathological studies, and biochemical assays. Docking and Simulation studies were performed to check the binding and stability with receptors progressing the chronic wound. From the column chromatography, B fraction has shown the presence of maximum polyphenolic content and as well as the polyphenol compounds such as quercetin, rutin and tannic acid as confirmed by the HPLC. Synthesize B fraction-AgNP were found to be below 100 nm in size and spherical in shape as per the characterization. No cytotoxic effect was observed on L929 cells treated with B fraction and its nanoparticles. Formulated B fraction-AgNP gel has revealed the better stability and earlier wound contraction, i.e. before the completion of 14 days of topical treatment. Histopathology studies and collagen content has confirmed the re-epithelization in skin wounds. MD simulation revealed the stability with PI3K and AKT. This can be concluded that tobacco stem polyphenol loaded nanoparticles has potent wound healing activity that can be utilized as nano-drug delivery system for suppression of chronic wound development. Communicated by Ramaswamy H. Sarma

A systematic review on wound healing

The body's initial line of defence, the skin protects the inside organs from heat, chemical, and mechanical harm. It has a highly developed immune system that protects the body from harmful illnesses. The body's natural response to tissue damage is wound healing. But wound healing is a complicated process that involves a wide range of cell types, cytokines, mediators, and the vascular system interacting with one another. It is a complex, strictly controlled process that is essential to retaining all other skin functions in addition to the skin's barrier function. Numerous factors, both modifiable and non-modifiable, can impact this process. In order to successfully restore the damaged tissue, wound healing is a dynamic process supported by a variety of cellular processes, including as homeostasis, inflammation, proliferation, and remodelling. These activities must be properly integrated with one another. When there is damage to the skin, bacteria can swiftly infiltrate the tissues behind the skin, leading to life-threatening infections and chronic wounds. Natural phytomedicines with significant pharmacological qualities have been used extensively and successfully to treat wounds and prevent infections. Phytotherapy has been used for millennia to effectively cure skin wounds and delay the formation of infections. This study focuses on cutaneous wound healing and highlights the classical wound healing phases because wound healing occurs in many regions of the human body. Changes in any one of these stages may encourage the development of chronic wounds and hinder their healing. Numerous plants have been shown to aid in wound healing through a variety of processes.

Nanoscale iodophoric poly(vinyl amide) coatings for the complexation and release of iodine for antimicrobial surfaces

Wound infection exacerbated by multidrug-resistant (MDR) bacteria has necessitated the need for wound dressing materials with embedded antimicrobial property to prevent the development of chronic wounds. Iodine (I2), typically as a poly(vinyl pyrrolidone)-I2 (PVP–I) complex, is a widely used antiseptic agent in wound care owing to its efficacy, safety, and low probability to cause further resistance. Despite extensive research on PVP–I formulations, there is potentially a large selection of poly(vinyl amide)s that have remained largely unexplored as iodophoric materials, particularly as coatings for wound dressings and medical devices. Therefore, in this study we prepared a series of stable, cross-linked poly(vinyl amide) coatings via plasma polymerization and studied their structure–property relationships for the complexation and release of I2. Plasma polymerized poly(N-vinyl-2-pyrrolidone) (pPVP), poly(N-methyl-N-vinylacetamide) (pPMVA) and poly(N-vinylcaprolactam) (pPVCl) nanoscale coatings were prepared with uniform thicknesses of 330–340 nm and low surface roughness. Complexation of I2 as polyiodides resulted in a significant increase in the pPVCl coating thickness in phosphate buffered saline (PBS), consistent with the Hofmeister effect. Raman spectroscopy confirmed that the I2 was complexed exclusively as the triiodide ion (I3-) in all coatings, which was confirmed by synchrotron X-ray photoelectron spectroscopy (XPS) experiments. Nuclear magnetic resonance (NMR) spectroscopy of poly(vinyl amides) was employed to further prove that the complexing species was hydrogen triiodide (HI3). The loading of I2 species increased from pPVP < pPMVA < pPVCl, with percentage elemental compositions of 1.3, 1.8, and 2.9%, respectively, which correlated with the extent of nitrogen loss during polymerization and oxidation, and was also in agreement with determined negative zeta potential values. However, quantification of the released I2 species over 5 h showed that the greatest release was observed from pPMVA (121.3 µg.cm−2), with pPVP (77.4 µg.cm−2) and pPVCl (74.6 µg.cm−2) releasing a similar amount, highlighting that I2 release from poly(vinyl amide) coatings is a function of the loading and composition of the polymer, not just the I2 complexing amide motif. The I2 complexed pPMVA coated wound dressings were highly effective against Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus, the two major strains associated with wound infection, reducing bacterial viability by up to 4 and 7 (log10 reduction) orders of magnitude. Overall, the poly(vinyl amide) coatings are promising iodophors for the prevention and treatment of wound infections.

Increased Levels of BAMBI Inhibit Canonical TGF-β Signaling in Chronic Wound Tissues.

Chronic wounds affect more than 2% of the population worldwide, with a significant burden on affected individuals, healthcare systems, and societies. A key regulator of the entire wound healing cascade is transforming growth factor beta (TGF-β), which regulates not only inflammation and extracellular matrix formation but also revascularization. This present work aimed at characterizing wound tissues obtained from acute and chronic wounds regarding angiogenesis, inflammation, as well as ECM formation and degradation, to identify common disturbances in the healing process. Serum and wound tissues from 38 patients (N = 20 acute and N = 18 chronic wounds) were analyzed. The patients' sera suggested a shift from VEGF/VEGFR to ANGPT/TIE2 signaling in the chronic wounds. However, this shift was not confirmed in the wound tissues. Instead, the chronic wound tissues showed increased levels of MMP9, a known activator of TGF-β. However, regulation of TGF-β target genes, such as CTGF, COL1A1, or IL-6, was absent in the chronic wounds. In wound tissues, all three TGF-β isoforms were expressed with increased levels of TGF-β1 and TGF-β3 and a reporter assay confirmed that the expressed TGF-β was activated. However, Western blots and immunostaining showed decreased canonical TGF-β signaling in the respective chronic wound tissues, suggesting the presence of a TGF-β inhibitor. As a potential regulatory mechanism, the TGF-β proteome profiler array suggested elevated levels of the TGF-β pseudo-receptor BAMBI. Also, tissue expression of BAMBI was significantly increased not only in chronic wounds (10.6-fold) but also in acute wounds that had become chronic (9.5-fold). In summary, our data indicate a possible regulatory role of BAMBI in the development of chronic wounds. The available few in vivo studies support our findings by postulating a therapeutic potential of BAMBI for controlling scar formation.

Electrospinning Nanofibers as a Dressing to Treat Diabetic Wounds.

Globally, diabetic mellitus (DM) is a common metabolic disease that effectively inhibits insulin production, destroys pancreatic β cells, and consequently, promotes hyperglycemia. This disease causes complications, including slowed wound healing, risk of infection in wound areas, and development of chronic wounds all of which are significant sources of mortality. With an increasing number of people diagnosed with DM, the current method of wound healing does not meet the needs of patients with diabetes. The lack of antibacterial ability and the inability to sustainably deliver necessary factors to wound areas limit its use. To overcome this, a new method of creating wound dressings for diabetic patients was developed using an electrospinning methodology. The nanofiber membrane mimics the extracellular matrix with its unique structure and functionality, owing to which it can store and deliver active substances that greatly aid in diabetic wound healing. In this review, we discuss several polymers used to create nanofiber membranes and their effectiveness in the treatment of diabetic wounds.

The physiological polyphosphate as a healing biomaterial for chronic wounds: Crucial roles of its antibacterial and unique metabolic energy supplying properties

• Wound healing, especially the healing of chronic wounds, requires an increased demand for metabolic energy (ATP). • The physiological polymer polyphosphate (polyP) is an efficient source for the generation of ATP during wound regeneration. • In addition, polyP undergoes coacervation, a process during which bacteria are killed. • These two pillars are the basis for the successful regeneration of chronic wounds in humans. Insufficient metabolic energy, in the form of adenosine triphosphate (ATP), and bacterial infections are among the main causes for the development of chronic wounds. Previously we showed that the physiological inorganic polymer polyphosphate (polyP) massively accelerates wound healing both in animals (diabetic mice) and, when incorporated into mats, in patients with chronic wounds. Here, we focused on a hydrogel-based gel formulation, supplemented with both soluble sodium polyP (Na-polyP) and amorphous calcium polyP nanoparticles (Ca-polyP-NP). Exposure of human epidermal keratinocytes to the gel caused a significant increase in extracellular ATP level, an effect that was even enhanced when Na-polyP was combined with Ca-polyP-NP. Furthermore, it is shown that the added polyP in the gel is converted into a coacervate, leading to encapsulation and killing of bacteria. The data on human chronic wounds showed that the administration of hydrogel leads to the complete closure of these wounds. Histological analysis of biopsies showed an increased granulation of the wounds and an enhanced microvessel formation. The results indicate that the polyP hydrogel, due to its properties to entrap bacteria and generate metabolic energy, is a very promising formulation for a new therapy for chronic wounds.

Diosmin-Loaded Nanoemulsion-Based Gel Formulation: Development, Optimization, Wound Healing and Anti-Inflammatory Studies.

The wound-healing process is complex and prone to interruption or failure, which can result in the development of chronic wounds that never heal. This can be overcome by seeking prompt medical attention, which will reduce the likelihood of complications and speed up the healing of the cutaneous wound. It has been established that functionalized engineered biomaterials are a possible strategy for starting skin wound care. The purpose of the current study is to develop a diosmin (DSM)-loaded nanoemulsion (NE)-based gel formulation and to investigate its wound healing and anti-inflammatory activity on rats. The DSM-loaded NEs (F1-F17) were developed and optimized with the help of Box-Behnken Design Expert. The DSM-Nes were developed using lauroglycol 90 (LG90®) as oil, Tween-80 as surfactant and transcutol-HP (THP) as co-surfactant. The optimized Nes showed globule size (41 ± 0.07 nm), polydispersity index (PDI) (0.073 ± 0.008) and percentage of entrapment efficiency (%EE) (87 ± 0.81%). This optimized DSM-loaded NEs (F1) was further evaluated and incorporated into 1% carbopol 940 gel. F1-loaded gel was then characterized for drug content, spreadability, in vitro release, wound healing, and anti-inflammatory studies. The developed gel of DSM was found to show significantly better (p < 0.05) wound-healing and anti-inflammatory activity.

Evaluation of in vitro anti-inflammatory effect of PLAY® on UC-MSCs: A COX-2 expression study

Wound healing is an intricate process consisting of multiple phases, each of which is indispensable for requisite tissue repair. Timely initiation and resolution of each overlapping phase is critical in aiding the wound healing cascade. A prolonged inflammatory phase causes overexpression of proteolytic mediators, resulting in extracellular matrix (ECM) degradation and increased oxidative stress. This imbalance in inflammatory mediators, ECM degradation, and upregulated levels of reactive oxygen species retards cell proliferation and migration, resulting in delayed tissue repair and the development of chronic wounds. Cyclooxygenase-2 (COX-2) is a potent inflammatory mediator that plays a pivotal role in the wound healing process at different stages of the tissue repair cascade. Overexpression of COX-2 during the tissue repair process impairs the wound healing cascade and contributes to the formation of chronic wounds. PLAY® is an in-house product of International Stem Cell Services Limited (iCREST) that is a human blood-platelet cocktail of natural growth factors and bioactive modulators. In our study, we hypothesized that PLAY® decreases inflammation in phorbol myristate acetate (PMA)- and 5-fluorouracil (5-FU)- stimulated umbilical cord derived mesenchymal stem cells (UC-MSCs) by downregulating COX-2 expression to its basal levels. We used an experimentally induced inflammatory in vitro model to produce enhanced COX-2 expression in mesenchymal stem cells (MSCs) and PLAY® showed a significant decrease in COX-2 levels in PMA induced UC-MSCs, providing evidence for an innate anti-inflammatory effect of PLAY® and a potential role in accelerated wound healing.

Új módszerek a sebkezelésben

The treatment of chronic wounds changed significantly in the last few decades. While in the past the availability of simple, traditional wound treatment materials, sterile mull sheets, gauze bandages, adhesive plasters, and melbromine wound disinfectants was often limited, nowadays these tools have been replaced by modern (often called intelligent) wound dressings and advanced technologies. The progress experienced in many fields of medicine can also be clearly seen in wound treatment. New materials, tools and methods have been developed, intensive research has been achieved to detect the development of chronic wounds, to get to know local and systemic processes, and to investigate the molecular background of wound healing. Large-scale developments can also be seen by the wound dressing manufacturing companies, industrial partners have carried out significant innovation - for the purpose of developing new products and their practical application.

Signaling pathways in cutaneous wound healing.

Wound healing is a very complex process, where variety of different pathways is activated, depending on the phase of healing. Improper or interrupted healing might result in development of chronic wounds. Therefore, novel approaches based on detailed knowledge of signalling pathways that are activated during acute or chronic cutaneous wound healing enables quicker and more effective healing. This review outlined new possibilities of cutaneous wound healing by modulation of some signalling molecules, e.g., gasotransmitters, or calcium. Special focus is given to gasotransmitters, since these bioactive signalling molecules that can freely diffuse into the cell and exert antioxidative effects. Calcium is an important booster of immune system and it can significantly contribute to healing process. Special interest is given to chronic wounds caused by diabetes mellitus and overcoming problems with the inflammation.

Efficacy of Paracrine Factors from Mesenchymal Stem Cells for Treating Biofilm-Infected Wounds in a Murine Model

Background: Chronic wounds are a serious medical condition affecting over 6 million people in the United States. Biofilms, which alter the host immune response and establish a microenvironment that prevents wound healing, are intimately associated with the development of chronic wounds. Current treatment options do not specifically target the underlying molecular mechanisms of biofilm pathology. Paracrine factors secreted by mesenchymal stem cells (MSCs) have been demonstrated to play an important role in wound healing. The objective of this study was to examine the effects of the paracrine factors secreted from MSCs on reducing infection and accelerating wound closure in biofilm-infected wounds.Methods: MSCs were cultured by seeding on an extracellular matrix (ECM). The supernatant from MSCs containing paracrine factors were applied to mature &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt; biofilms &lt;i&gt;in vitro&lt;/i&gt; and the number of viable bacteria were quantitated. BALB/cJ mice were wounded and infected with &lt;i&gt;P. aeruginosa&lt;/i&gt; biofilms and the paracrine factors from reprogrammed MSCs were applied topically. The wound surface area and colony forming units counts of the treatment group were compared to control (culture media) and biofilm (untreated) groups. Results: The paracrine factors from MSCs grown on ECM were found to reduce &lt;i&gt;P. aeruginosa&lt;/i&gt; biofilm growth significantly (P&lt;0.01). Wounds in the treatment group had lower bacterial counts and an increased rate of wound closure compared to non-treated mice wounds. Conclusion: The results indicate that paracrine factors from reprogrammed MSCs accelerated wound healing and reduced the bacterial burden in biofilm-infected wounds. Future studies are needed to further characterize this phenomenon.

Reduced Glutathione Antioxidant Stability in Polymer Solutions Toward Wound Bioactive Dressing Application

Reduced glutathione (GSH) is incorporated in polymeric wound dressings to prevent oxidative stress-induced cellular damage and the development of chronic wounds. The present study investigates the influence of polyvinyl alcohol (PVA), polyethylene oxide (PEO), and PVA/PEO blend polymeric solutions on the stability of GSH during the preparations or storage. The stability was studied in three concentrations which were 3%, 5% and 8%, after sometimes between 0 to 7 days. The level of GSH achieved the highest electron donor activity at day 7 in 8% PVA/PEO (95.42%) and 8% PVA (94.27%) solutions, whereas GSH activity decreased when incorporated with PEO solutions. Such a decrease in the GSH activity due to PEO being less water-resistant and hydrolytic degradation susceptibility could expose the GSH to an aqueous environment and lead to the loss of GSH activity. In conclusion, a higher concentration of polymer and less-water resistant polymers can shield the GSH from an aqueous environment and maintain its stability in the polymer solutions used in wound dressing applications.

53. Wound Edge Inversion Delays Healing and Contributes to Dystrophic Scar Formation in a Mouse Model

Purpose: Management of dystrophic scars often requires surgical excision in the delayed periods as there are few reliable options to prophylax against the formation off dystrophic scars during physiologic or pathologic wound healing. This is in part because of limitations in the availability of genetically tractable small-animal models which can reliably generate the desired dystrophic tissue architecture. While using small animal models of wound healing is desired, the nature of murine dermal healing through contracture makes it poorly suited to the study of later wound sequalae such as dystrophic scars. We have previously demonstrated that tissue-edge inward folding mimicking the architecture of epibole mitigates contracture, restricts epithelialization, and prolongs wound opening. Here we demonstrate that murine epibolous wounds generate an environment of sustained inflammatory infiltration and proliferative granulation and ultimately generate consistent and reliable dystrophic scars in mice. Methods: Male C57BL/6J control (wt/wt) and diabetic (db/db) mice received bilateral 6mm excisional wounds. Each wound was stratified as either untreated control or chronic model. Chronic wounds were generated by incising skin flaps, which were sutured to the dermis side to create a folded skin edge. A first (acute) cohort was s were maintained for 14-days until all control wounds had closed and/or epithelialized and were harvested for flow cytometry for neutrophils and/or macrophages and/or histology for pan-keratin (epithelium) and alpha-smooth-muscle actin (myofibroblasts). A second (delayed) cohort was maintained until closure up to 63 days. Photographs were taken at time of sacrifice and samples were collected for H&E and Masson’s Trichrome Stain. Results: The epibolous wound environment maintained prolonged neutrophil-dominant inflammatory infiltrate up to 2-weeks with simultaneous enrichment of macrophage/monocyte populations (p<0.05). Epibolous wounds demonstrated reduced frequency of epithelialization as defined by pan-keratin signaling. In epibolous wounds without epithelialization, strong alpha-smooth-muscle actin signal was noted. When allowed to proceed to maturation, scars from epibole injuries remained significantly larger (p<0.05). This was true in both control and diabetic models. All wound-edge inversion injuries demonstrated gross and histologic evidence of dystrophic healing and collagen deposition compared to controls. Conclusion: Previously we demonstrated that wound-edge inversion to mimic epibole prolongs wound opening. Here we demonstrate that this translates to prolongs inflammation and a transition of murine healing to a more human-relevant granulation pattern. Furthermore, the delay of closure results in a consistent dystrophic scar without need for thermal, radiological, chemical or biological interference. Consequently, this simple surgical maneuver enhances our ability to study and intervene in the process of acute and chronic wound development and dystrophic scar formation in a histologically humanized model while retaining access to the genetic tractability of murine stock.

The Role of Puerarin in Chronic Wounds: A Review of its Mechanism of Action and Potential Novel Applications.

Chronic wounds have a high disease burden and significantly influence patient quality of life. The development of chronic wounds is multifactorial and thus adequate management and care is often difficult to achieve. Chronic diseases, malnutrition, smoking, immune dysregulation, and age contribute to chronic wound development. Treatment options include adequately addressing underlying conditions and selecting appropriate topical preparations which enhance and promote healing of different wounds based on an understanding of wound healing pathophysiology. Puerarin, a naturally occurring flavinoid, may offer therapeutic potential for addressing etiologies as well as managing wound beds due to its anti-inflammatory, anti-oxidative, pro-angiogenic, and anesthetic properties.

Resveratrol-Induced Signal Transduction in Wound Healing.

Resveratrol is a well-known polyphenol that harbors various health benefits. Besides its well-known anti-oxidative potential, resveratrol exerts anti-inflammatory, pro-angiogenic, and cell-protective effects. It seems to be a promising adjuvant for various medical indications, such as cancer, vascular, and neurodegenerative diseases. Additionally, resveratrol was shown to display beneficial effects on the human skin. The polyphenol is discussed to be a feasible treatment approach to accelerate wound healing and prevent the development of chronic wounds without the drawback of systemic side effects. Despite resveratrol’s increasing popularity, its molecular mechanisms of action are still poorly understood. To take full advantage of resveratrol’s therapeutic potential, a profound knowledge of its interactions with its targets is needed. Therefore, this review highlights the resveratrol-induced molecular pathways with particular focus on the most relevant variables in wound healing, namely inflammation, oxidative stress, autophagy, collagen proliferation and angiogenesis.

Experimental Study of the Effect of Photobiomodulation Therapy on the Regulation of the Healing Process of Chronic Wounds

Currently, wound treatment is an urgent task of medicine around the world. In the process of wound healing, various types of cells are involved under the control and regulation of cytokines and growth factors. Disruption of the synchronization process between the various types of cells and intercellular mediators involved in the restoration of tissue damage can lead to impaired healing and the development of chronic wounds. Photobiomodulation (PBM) therapy promotes platelet activation and aggregation, reduces inflammation and oxidative stress, and accelerates cell migration and proliferation. PBM also induces the production of the extracellular matrix and the release of key growth factors, thereby improving tissue regeneration and accelerating wound healing. The aim of our work was to study the effect of photobiomodulation therapy on the regulation of reparative processes in chronic wounds monitored by biomarkers and platelet aggregation activity. 54 Wistar rats were divided into three groups. Intact animals were not manipulated. In animals of the control and experimental groups, a chronic wound was simulated by reproducing the conditions of local hypoxia and microcirculation disorders. The wounds of the experimental group received PBM therapy. The device Lika-therapist M (Ukraine) was used in a continuous mode at a wavelength of 660 nm, an output power of 10 mW, and an energy density of 1 J/cm2. The wounds of the animals in the control group were treated with sham. The animals were euthanized on days 3, 7, 14, and 28 after the surgery (6 animals, each from the control and experimental groups). Measurements of the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), the basic fibroblast growth factor (bFGF), and reactive oxygen species (ROS) were carried out by ELISA. Results revealed the multidirectional effect of PBM therapy on the expression of the studied biomarkers. The results of the histological examination indicated a positive effect of PBM therapy with the applied parameters on the repair processes of chronic wounds. We concluded that the use of PBM therapy made it possible to regulate disturbances in reparative processes by modulating ROS, cytokines, and platelet aggregation activity.

Fluorescent light energy modulates healing in skin grafted mouse model.

Skin grafting is often the only treatment for skin trauma when large areas of tissue are affected. This surgical intervention damages the deeper dermal layers of the skin with implications for wound healing and a risk of scar development. Photobiomodulation (PBM) therapy modulates biological processes in different tissues, with a positive effect on many cell types and pathways essential for wound healing. This study investigated the effect of fluorescent light energy (FLE) therapy, a novel type of PBM, on healing after skin grafting in a dermal fibrotic mouse model. Split-thickness human skin grafts were transplanted onto full-thickness excisional wounds on nude mice. Treated wounds were monitored, and excised xenografts were examined to assess healing and pathophysiological processes essential for developing chronic wounds or scarring. Results demonstrated that FLE treatment initially accelerated re-epithelialization and rete ridge formation, while later reduced neovascularization, collagen deposition, myofibroblast and mast cell accumulation, and connective tissue growth factor expression. While there was no visible difference in gross morphology, we found that FLE treatment promoted a balanced collagen remodeling. Collectively, these findings suggest that FLE has a conceivable effect at balancing healing after skin grafting, which reduces the risk of infections, chronic wound development, and fibrotic scarring.

Wound Healing: A Comprehensive Review.

Wound healing is an intricate, tightly regulated process that is critical to maintaining the barrier function of skin along with preserving all other skin functions. This process can be influenced by a variety of modifiable and nonmodifiable factors. As wound healing takes place in all parts of the human body, this review focuses on cutaneous wound healing and highlights the classical wound healing phases. Alterations in any of these phases can promote chronic wound development and may impede wound healing.