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Electric Factors in Wound Healing
Abstract
Significance:
Electric factors such as electric charges, electrodynamic field, skin battery and interstitial exclusion permeate wound healing physiology and physiopathology from injury to reepithelialization. The understanding of how electric factors contribute to wound healing and how treatments may interfere with them is fundamental for the development of better strategies for the management of pathological scarring and chronic wounds. Recent Advances: Angiogenesis, cell migration, macrophage activation hemorheology and microcirculation can interfere and be interfered with electric factors. New treatments with various types of electric currents, laser, LED, acupuncture and weak electric fields applied directly on the wound have been developed in order to improve wound healing.
Critical issues:
Despite the basic and clinical development, pathological scars as keloids and chronic wounds are still a challenge. Future Directions New treatments can be developed to improve skin wound healing taking into account the influence of electrical charges. Monitoring electrical activity during skin healing and the influence of treatments on hemorheology and microcirculation are examples of how to use knowledge of electrical factors to increase their effectiveness.
... Similar to endogenous EF, exogenous physiological EFs have also been widely developed to facilitate wound healing. 8,11 Some studies have shown that electric stimulation can promote the migration of keratinocytes 12,13 along with the proliferation and secretion of fibroblasts. [14][15][16] However, relatively only a few studies have focused on the effect of EF on macrophages. ...
... H&E-stained images were displayed in Fig. 8a, showing lesions discerned by the boundary between the normal epidermises and Fig. 8c, the scar lengths were significantly shorter in the 10, 100, and 1,000 ls pulse width groups compared to that of the control group. Electrical stimulation has been proven to improve scarring, 11 and a decrease in the scar area is necessary to ensure rapid recovery of the wound area for subsequent growth of hair follicles and nerve endings. 34,35 The control group exhibited a local bleeding area (indicated by a five-pointed star) and inflammatory cell mass (marked with a diamond), which were not observed in the PCCEF groups. ...
Objectives: Accelerating wound healing using continuous exogenous electrical stimulation is limited due to some serious side effects, including thermal damage. Many previous studies based on direct current contact stimulation may cause chemical burns or blisters, thereby increasing patients suffering. The aim of this study was to develop a safer and more convenient pulse capacitive coupling electrical field (PCCEF) stimulation to accelerate wound healing.
Approach: A PCCEF-generating platform was self-designed to facilitate wound healing. The promoting effects and appropriate pulse width were explored by applying PCCEFs (54 mV/mm, 60 Hz) of different pulse widths to various cells involved in wound healing and mouse models for 2 h daily.
Results: PCCEFs of ≥10 μs pulse width showed marked promotion of the migration and proliferation of human dermal fibroblasts and HaCaT cells, enhanced the M2-type polarization and YPA/TAZ expression of macrophages, and facilitated the wound healing of mouse models. Comprehensive histological results suggested that PCCEF of 100 μs pulse width exerted the most positive effects.
Innovation: A safe and effective PCCEF was developed to promote wound healing, which prevented prolonged stimulation and averted direct contact.
Conclusion: PCCEF accelerated wound healing, especially at the optimal 100 μs pulse width, and was expected to be translated to clinical application, helping alleviate patient suffering, while reducing side effects.
... Natural cell and tissue homeostasis generally takes place in the presence of mesoscopic fields up to the order of 10 V/cm. Intact skin, for instance, presents a transcutaneous potential difference ranging between about 15 to 40 mV, called the skin battery, which varies according to the anatomical site [180][181][182]. The skin surface maintains a negative potential relative to the dermis, generated and sustained by active Na + /K + ATPase pumps in the epidermis. ...
... This lateral field plays an essential role in the wound healing, and disrupting it also disrupts the healing process [183,184]. During the healing process, the lateral field declines and can therefore be used as a noninvasive indicator for the recovery stadium [182,185]. Analogous relationships are expected for burning wounds, although the healing process is likely complicated in this case by dead tissues at the injury, contamination and infection [181]. Remarkably, chronic wounds display a weaker lateral electric field than acute lesions, likely contributing to delayed healing [186,187]. ...
Cold atmospheric plasma and nanomedicine originally emerged as individual domains, but are increasingly applied in combination with each other. Most research is performed in the context of cancer treatment, with only little focus yet on the possible synergies. Many questions remain on the potential of this promising hybrid technology, particularly regarding regenerative medicine and tissue engineering. In this perspective article, we therefore start from the fundamental mechanisms in the individual technologies, in order to envision possible synergies for wound healing and tissue recovery, as well as research strategies to discover and optimize them. Among these strategies, we demonstrate how cold plasmas and nanomaterials can enhance each other’s strengths and overcome each other’s limitations. The parallels with cancer research, biotechnology and plasma surface modification further serve as inspiration for the envisioned synergies in tissue regeneration. The discovery and optimization of synergies may also be realized based on a profound understanding of the underlying redox- and field-related biological processes. Finally, we emphasize the toxicity concerns in plasma and nanomedicine, which may be partly remediated by their combination, but also partly amplified. A widespread use of standardized protocols and materials is therefore strongly recommended, to ensure both a fast and safe clinical implementation.
... One of the most important applications of Li is in energy storage as Li-ion batteries, which are the most promising electrochemical energy storage devices [161]. Electrotherapy creates new opportunities in wound healing [162], and wearable ionic triboelectric nanogenerator (iTENG) patches (created from a stretchable platform based on LiCl-loaded organogels and elastomeric microtubular structures) utilized the therapeutic effects of Li-ions in wound healing, and moreover contributed to creating and transmitting electrical stimulation ( Figure 4) [163], which is very promising in wound healing applications [164]. conduit on a rat sciatic nerve injury was observed to increase nerve regeneration in rats [172]. ...
... t. Biomater. 2022, 13,162 10 of 28 ...
Lithium (Li) is a metal with critical therapeutic properties ranging from the treatment of bipolar depression to antibacterial, anticancer, antiviral and pro-regenerative effects. This element can be incorporated into the structure of various biomaterials through the inclusion of Li chloride/carbonate into polymeric matrices or being doped in bioceramics. The biocompatibility and multifunctionality of Li-doped bioceramics present many opportunities for biomedical researchers and clinicians. Li-doped bioceramics (capable of immunomodulation) have been used extensively for bone and tooth regeneration, and they have great potential for cartilage/nerve regeneration, osteochondral repair, and wound healing. The synergistic effect of Li in combination with other anticancer drugs as well as the anticancer properties of Li underline the rationale that bioceramics doped with Li may be impactful in cancer treatments. The role of Li in autophagy may explain its impact in regenerative, antiviral, and anticancer research. The combination of Li-doped bioceramics with polymers can provide new biomaterials with suitable flexibility, especially as bio-ink used in 3D printing for clinical applications of tissue engineering. Such Li-doped biomaterials have significant clinical potential in the foreseeable future.
... This study presents significant findings regarding the effects of a 10 kV/m EF on a rat PI model, specifically detailing the relationships between histopathological parameters and the expression levels of growth factors (EGF, FGF2, VEGF, and eNOS) that are critical in wound healing. These markers play crucial roles in cell proliferation, angiogenesis, and tissue repair, offering insights into how their modulation over the treatment duration correlates with observed wound healing outcomes [20,21,25,26]. ...
Background: Pressure injuries are still an important health problem worldwide, although many therapies have been applied to date. This study aimed to determine the optimal duration of external application of a 10 kV/m direct current (DC, static) electric field in a pressure injury model in rats. Methods: Twelve male Wistar–Albino rats were divided into three groups: Grade-1, Grade-2, and Grade-3. Two round magnets were placed 4 h daily for one day in Grade-1, two days in Grade-2, and three days in Grade-3. Following wound formation, one rat from each group was designated the control, while the other rats were exposed to a 10 kV/m electric field for 15, 30, or 60 min. Results: Histopathological improvements were observed after 15 and 30 min of application, whereas a sharp decrease in the gene expression of growth factors at 30 min revealed that 15 min of application was optimal overall. Conclusions: According to the results of this study, 15 min applications of an external 10 kV/m electric field are promising for providing satisfactory results in wound healing. Further studies should examine in greater detail the effects of electric fields on growth factors and the mechanisms underlying these responses.
... Xie et al. further modeled this phenomenon in COMSOL, showing that aligned electrospun PVDF nanofibers produced a voltage of -21 mV under an approximate force of 10 nN force, compared to 18.9 mV for randomly oriented fibers verifying with measuring intracellular calcium levels [101,102]. Annealing PVDF-TrFE scaffolds at 140°C maximizes their energy harvesting potential, allowing them to generate electrical stimulation signals in the range of endogenous-like electrical fields (20 -300 mV/m) similar to those observed in human skin wounds under similar force and deformation estimates of nanofibers [103][104][105][106]. Thus, we expect PVDF-TrFE scaffolds annealed at 140°C to produce an even higher level of electrical response compared to PVDF and NT groups under similar activation forces. ...
This study investigates bioelectric stimulation's role in tissue regeneration by enhancing the piezoelectric properties of tissue-engineered grafts using annealed poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) scaffolds. Annealing at temperatures of 80°C, 100°C, 120°C, and 140°C was assessed for its impact on material properties and physiological utility. Analytical techniques such as Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) revealed increased crystallinity with higher annealing temperatures, peaking in β-phase content and crystallinity at 140°C. Scanning Electron Microscopy (SEM) showed that 140°C annealed scaffolds had enhanced lamellar structures, increased porosity, and maximum piezoelectric response. Mechanical tests indicated that 140°C annealing improved elastic modulus, tensile strength, and substrate stiffness, aligning these properties with physiological soft tissues. In vitro assessments in Schwann cells demonstrated favorable responses, with increased cell proliferation, contraction, and extracellular matrix attachment. Additionally, genes linked to extracellular matrix production, vascularization, and calcium signaling were upregulated. The foreign body response in C57BL/6 mice, evaluated through Hematoxylin and Eosin (H&E) and Picrosirius Red staining, showed no differences between scaffold groups, supporting the potential for future functional evaluation of the annealed group in tissue repair.
... Many physiological processes are due to internal electrical factors. These effects can apparently be positively influenced by the application of electrical stimulation [35], including an increase in microcirculation [36] and formation of intracellular pores [37]. In contrast, our data show that microcirculation enhancement was not exclusively caused by the electric fields, but that at least one other plasma component was required. ...
Cold atmospheric plasma (CAP) has been shown to be beneficial in various medical fields such as wound healing, oncology or dentistry. A prominent effect induced by CAP is the boost of microcirculation in human skin tissue. Being a complex cocktail of physical and chemically reactive components, the mechanisms by which CAP enhances microcirculation still remain unclear. Thus, this study aims to identify relevant CAP components involved in stimulation of dermal microcirculation. In a comparative approach, the application of the same CAP source was modified in such a way that three different treatment modalities could be realized, each with a characteristic composition of electrical current flow and concentration of reactive species. Microcirculation parameters oxygen saturation (StO2), tissue hemoglobin index, near-infrared perfusion index and tissue water index were recorded before and after each treatment on the lateral proximal left arm of 10 healthy volunteers by means of hyperspectral imaging. The maximum microcirculatory response to CAP was observed when all components were allowed to interact with skin tissue (standard treatment). In contrast, no upregulation was found as soon as electric currents and fields had been removed from the effective component spectrum. Application of the CAP source at reduced concentrations of reactive species compared to standard treatment led to significant but less pronounced enhancement of dermal microcirculation. The findings of this study indicate that a synergistic interplay of all CAP components promotes microcirculation in dermal tissue most effectively. Moreover, the findings support the hypothesis that electric currents and fields play a key role in enabling microcirculation boost whereas availability of reactive species in the gas phase is associated with the intensity of the tissue response to CAP treatment.
... For example, the visualization of the cell membrane surface charge can be used for clinical cytological diagnosis [4,5]. Monitoring the charge distribution of tissues could predict its associated wound healing process [6,7]. The surface charge of materials enables their functions in directing cell attachment, mobility, proliferation, differentiation, signaling and protein adsorption [8][9][10][11]. ...
Rapid surface charge mapping of a solid surface remains a challenge. In this study, we present a novel microchip based on liquid crystals for assessing the surface charge distribution of a planar or soft surface. This chip enables rapid measurements of the local surface charge distribution of a charged surface. The chip consists of a micropillar array fabricated on a transparent indium tin oxide substrate, while the liquid crystal is used to fill in the gaps between the micropillar structures. When an object is placed on top of the chip, the local surface charge (or zeta potential) influences the orientation of the liquid crystal molecules, resulting in changes in the magnitude of transmitted light. By measuring the intensity of the transmitted light, the distribution of the surface charge can be accurately quantified. We calibrated the chip in a three-electrode configuration and demonstrated the validity of the chip for rapid surface charge mapping using a borosilicate glass slide. This chip offers noninvasive, rapid mapping of surface charges on charged surfaces, with no need for physical or chemical modifications, and has broad potential applications in biomedical research and advanced material design.
... Bioelectricity is a basic attribute of living organisms and is necessary for regulating the vascular network during embryonic development, tissue repair, and tumor progression [10][11][12]. Thus, regulating the bioelectric balance of blood vessels might be an alternative strategy for normalizing tumor vasculature. ...
Pathological angiogenesis frequently occurs in tumor tissue, limiting the efficiency of chemotherapeutic drug delivery and accelerating tumor progression. However, traditional vascular normalization strategies are not fully effective and limited by the development of resistance. Herein, inspired by the intervention of endogenous bioelectricity in vessel formation, we propose a wireless electrical stimulation therapeutic strategy, capable of breaking bioelectric homeostasis within cells, to achieve tumor vascular normalization. Polarized barium titanate nanoparticles with high mechano-electrical conversion performance were developed, which could generate pulsed open-circuit voltage under low-intensity pulsed ultrasound. We demonstrated that wireless electrical stimulation significantly inhibited endothelial cell migration and differentiation in vitro. Interestingly, we found that the angiogenesis-related eNOS/NO pathway was inhibited, which could be attributed to the destruction of the intracellular calcium ion gradient by wireless electrical stimulation. In vivo tumor-bearing mouse model indicated that wireless electrical stimulation normalized tumor vasculature by optimizing vascular structure, enhancing blood perfusion, reducing vascular leakage, and restoring local oxygenation. Ultimately, the anti-tumor efficacy of combination treatment was 1.8 times that of the single chemotherapeutic drug doxorubicin group. This work provides a wireless electrical stimulation strategy based on the mechano-electrical conversion performance of piezoelectric nanoparticles, which is expected to achieve safe and effective clinical adjuvant treatment of malignant tumors.
Numerous studies have demonstrated the efficacy of extremely low frequency‐pulsed electromagnetic fields (ELF‐PEMF) in accelerating the wound healing process in vitro and in vivo. Our study focuses specifically on ELF‐PEMF applied with the Magnomega® device and aims to assess their effect during the main stages of the proliferative phase of dermal wound closure, in vitro. Thus, after the characterization of the EMFs delivered by the Magnomega® unit, primary culture of human dermal fibroblasts (HDFs) were exposed, or not for the control culture, to 10–12 and 100 Hz ELF‐PEMF. These parameters are used in clinical practice by physiotherapists in order to enhance healing of dermal lesions in patients. HDFs proliferation was first assessed and revealed an increase in the expression of one of the two genetic markers of cell proliferation tested (PCNA and MKI67), after initial exposure of the cells to 10–12 Hz PEMF. Next, migration of HDFs was investigated by performing scratch assays on HDF layers. The observed wound closure kinetics corroborate the early organization of actin stress fibers that was revealed in the cytoplasm of HDFs exposed to 100 Hz ELF‐PEMF. Also, maturation of HDFs into myofibroblasts was significantly increased in cells exposed to 10–12 or to 100 Hz PEMF. The present study is the first to demonstrate, in vitro, an early stimulation of HDFs, after their exposure to ELF‐PEMF delivered by the Magnomega® device, which could contribute to an acceleration of the wound healing process.
Spinal cord injury, traumatic brain injury, and neurosurgery procedures usually lead to neural tissue damage. Self‐assembled peptide (SAP) hydrogels, a type of innovative hierarchical nanofiber‐forming peptide sequences serving as hydrogelators, have emerged as a promising solution for repairing tissue defects and promoting neural tissue regeneration. SAPs possess numerous features such as adaptable morphologies, biocompatibility, injectability, tunable mechanical stability, and mimicking of the native extracellular matrix. This review explores the capacity of neural cells regeneration and examines the critical aspects of SAPs in neuroregeneration, including their biochemical composition, topology, mechanical behavior, conductivity, and degradability. Additionally, we delve into the latest strategies involving SAPs for central or peripheral neural tissue engineering. Finally, we discuss the future prospects of SAP hydrogel design and development in the realm of neuroregeneration.
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The treatment of chronic refractory wounds poses significant challenges and threats to both human society and the economy. Existing research studies demonstrate that electrical stimulation fosters cell proliferation and migration and promotes the production of cytokines that expedites the wound healing process. Presently, clinical settings utilize electrical stimulation devices for wound treatment, but these devices often present issues such as limited portability and the necessity for frequent recharging. A cutting-edge wound dressing employing the piezoelectric effect could transform mechanical energy into electrical energy, thereby providing continuous electrical stimulation and accelerating wound healing, effectively addressing these concerns. This review primarily reviews the selection of piezoelectric materials and their application in wound dressing design, offering a succinct overview of these materials and their underlying mechanisms. This study also provides a perspective on the current limitations of piezoelectric wound dressings and the future development of multifunctional dressings harnessing the piezoelectric effect.
Multifunctional hydrogel adhesives inhibiting infections and enabling the electrical stimulation (ES) of tissue reparation are highly desirable for the healing of surgical wounds and other skin injuries. Herein, a therapeutic nanocomposite hydrogel is designed by integrating β‐cyclodextrin‐embedded Ag nanoparticles (CDAgNPs) in a polyvinyl alcohol (PVA) matrix enhanced with free β‐cyclodextrin (CD) and an atypical macromolecule made of β‐glucan grafted with hyaluronic acid (HAG). The main objective is to develop a biocompatible dressing combining the electroconductivity and antibacterial activity of CDAgNPs with the cohesiveness and porosity of PVA and the anti‐inflammatory, moisturizing, and cell proliferation‐promoting properties of HAG. The last component, CD, is added to strengthen the network structure of the hydrogel. PVA/CD/HAG/CDAgNP exhibited excellent adhesion strength, biocompatibility, electroconductivity, and antimicrobial activity against a wide range of bacteria. In addition, the nanocomposite hydrogel has a swelling ratio and water retention capacity suitable to serve as a wound dressing. PVA/CD/HAG/CDAgNP promoted the proliferation of fibroblast in vitro, accelerated the healing of skin wounds in an animal model, and is hemostatic. Upon ES, the PVA/CD/HAG/CDAgNP nanocomposite hydrogel became more efficient both in vitro and in vivo further speeding up the skin healing process thus demonstrating its potential as a next‐generation electroconductive wound dressing.
Diabetic foot ulcer (DFU) is a major complication of diabetes and is associated with a high risk of lower limb amputation and mortality. During their lifetime, 19%–34% of patients with diabetes can develop DFU. It is estimated that 61% of DFU become infected and 15% of those with DFU require amputation. Furthermore, developing a DFU increases the risk of mortality by 50%–68% at 5 years, higher than some cancers. Current standard management of DFU includes surgical debridement, the use of topical dressings and wound decompression, vascular assessment, and glycemic control. Among these methods, local treatment with dressings builds a protective physical barrier, maintains a moist environment, and drains the exudate from DFU wounds. This review summarizes the development, pathophysiology, and healing mechanisms of DFU. The latest research progress and the main application of dressings in laboratory and clinical stage are also summarized. The dressings discussed in this review include traditional dressings (gauze, oil yarn, traditional Chinese medicine, and others), basic dressings (hydrogel, hydrocolloid, sponge, foam, film agents, and others), bacteriostatic dressings, composite dressings (collagen, nanomaterials, chitosan dressings, and others), bioactive dressings (scaffold dressings with stem cells, decellularized wound matrix, autologous platelet enrichment plasma, and others), and dressings that use modern technology (3D bioprinting, photothermal effects, bioelectric dressings, microneedle dressings, smart bandages, orthopedic prosthetics and regenerative medicine). The dressing management challenges and limitations are also summarized. The purpose of this review is to help readers understand the pathogenesis and healing mechanism of DFU, help physicians select dressings correctly, provide an updated overview of the potential of biomaterials and devices and their application in DFU management, and provide ideas for further exploration and development of dressings. Proper use of dressings can promote DFU healing, reduce the cost of treating DFU, and reduce patient pain.
Chronic wounds and scar formation are widespread due to limited suitable remedies. The macrophage is a crucial regulator in wound healing, controlling the onset and termination of inflammation and regulating other processes related to wound healing. The current breakthroughs in developing new medications and drug delivery methods have enabled the accurate targeting of macrophages in oncology and rheumatic disease therapies through clinical trials. These successes have cleared the way to utilize drugs targeting macrophages in various disorders. This review thus summarizes macrophage involvement in normal and pathologic wound healing. It further details the targets available for macrophage intervention and therapeutic strategies for targeting the behavior of macrophages in tissue repair and regeneration.
In this study, a conductive composite material, based on graphene oxide (GO), nanocellulose (CNF), and tannins (TA) from pine bark, reduced using polydopamine (PDA), was developed for wound dressing. The amount of CNF and TA was varied in the composite material, and a complete characterization including SEM, FTIR, XRD, XPS, and TGA was performed. Additionally, the conductivity, mechanical properties, cytotoxicity, and in vitro wound healing of the materials were evaluated. A successful physical interaction between CNF, TA, and GO was achieved. Increasing CNF amount in the composite reduced the thermal properties, surface charge, and conductivity, but its strength, cytotoxicity, and wound healing performance were improved. The TA incorporation slightly reduced the cell viability and migration, which may be associated with the doses used and the extract’s chemical composition. However, the in-vitro-obtained results demonstrated that these composite materials can be suitable for wound healing.
Poor wound healing on the face and neck can lead to significant morbidity and dissatisfaction in facial plastic surgery. With current advances in wound healing management and commercially available biologic and tissue-engineered products, there are several options available to optimize acute wound healing and treat delayed or chronic wounds. This article summarizes some of the key principals and recent developments in wound healing research in addition to potential future advancements in the field of soft tissue wound healing.
Plant extracts have been evaluated to determine their bioactivities and their potential use in wound healing. In this study, a conductive composite material, based on graphene oxide (GO), nanocellulose (CNF) and tannins (TA) from pine bark, reduced using polydopamine (PDA), was developed for wound dressing. The amount of CNF and TA was varied in the composite material and a complete characterization including SEM, FTIR, XRD, XPS, TGA was performed. Also, the conductivity, mechanical properties, cytotoxicity, and in vitro wound healing of the materials were evaluated. The results showed a successful physical interaction between CNF, TA and GO. In-creasing the CNF amount in the composite reduced the thermal properties, surface charge and conductivity of the material, but its strength, cytotoxicity and wound healing performance were improved. The TA incorporation slightly reduced the cell viability and migration, which may be associated with the doses used and the chemical composition of the extracts. However, the in vitro obtained results demonstrated that these composite materials can be suitable for wound healing.
Wound healing is characterized by complex, orchestrated, spatiotemporal dynamic processes. Recent findings demonstrated suitable local microenvironments were necessities for wound healing. Wound microenvironments include various biological, biochemical and physical factors, which are produced and regulated by endogenous biomediators, exogenous drugs, and external environment. Successful drug delivery to wound is complicated, and need to overcome the destroyed blood supply, persistent inflammation and enzymes, spatiotemporal requirements of special supplements, and easy deactivation of drugs. Triggered by various factors from wound microenvironment itself or external elements, stimuli-responsive biomaterials have tremendous advantages of precise drug delivery and release. Here, we discuss recent advances of stimuli-responsive biomaterials to regulate local microenvironments during wound healing, emphasizing on the design and application of different biomaterials which respond to wound biological/biochemical microenvironments (ROS, pH, enzymes, glucose and glutathione), physical microenvironments (mechanical force, temperature, light, ultrasound, magnetic and electric field), and the combination modes. Moreover, several novel promising drug carriers (microbiota, metal-organic frameworks and microneedles) are also discussed.
Insufficient angiogenesis frequently occurs after the implantation of orthopedic materials, which greatly increases the risk of bone defect reconstruction failure. Therefore, the development of bone implant with improved angiogenic properties is of great importance. Mimicking the extracellular matrix clues provides a more direct and effective strategy to modulate angiogenesis. Herein, inspired by the bioelectrical characteristics of the bone microenvironment, a piezoelectric bioactive glasses composite (P‐KNN/BG) based on the incorporation of polarized potassium sodium niobate is constructed, which could effectively promote angiogenesis. It is found that P‐KNN/BG has exceptional wireless electrical stimulation performance and sustained active ions release. In vitro cell experiments reveal that P‐KNN/BG enhances endothelial cell adhesion, migration, and differentiation via activating the eNOS/NO signaling pathway, which might be contributed to cell membrane hyperpolarization induced by wireless electrical stimulation increase the influx of active ions into the cells. In vivo chick chorioallantoic membrane experiment demonstrates that P‐KNN/BG shows excellent pro‐angiogenic capacity and biocompatibility. This work broadens the current understanding of bioactive materials with bionic electrical properties, which brings new insights into the clinical treatment of bone defect repair.
Surface potential of biomaterials is found to be important for wound healing. Here, poly(vinylidenefluoride-co-trifluoroethylene) (P(VDF-TrFE)) films with different surface potentials and piezoelectric responses were prepared and explored for the effect of surface potential on wound healing. The crystalline state of P(VDF-TrFE) films were characterized with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier-transformed infrared spectroscopy (FTIR), illustrated that the electric polarization will promote the crystallization of the β phase of P(VDF-TrFE), in which the content of β phase increased from 82.9% to 86.8% compared with the control. Then, Kelvin potential and piezoelectric coefficient d33 were to evaluate surface potential and polarization performance. Moreover, bovine serum albumin (BSA) adsorption and cell culture results showed that high surface potential can promote protein adsorption as well as fibroblast proliferation and macrophage polarization. Finally, in vivo experiments indicated that high voltage polarized P(VDF-TrFE) films can generate higher dynamic potential up to 2.3 V, and promoted wound healing from the phases of inflammation, proliferation and remodeling, the wound healing rate of which was 88.8% ± 0.8%, significantly higher than 79.1% ± 2.5% and 86.4% ± 1.8% of blank and control. In general, this work revealed that polarized P(VDF-TrFE) films can promote wound healing, shed light on designing wound healing materials with similar properties.
Collecting and utilizing various cytokines released by trauma and implantable materials for stimulating the body in producing a robust immune-inflammatory response would be a promising method. Therefore, an injectable “cytokine reservoir” hydrogel for cytokine management during tissue repair was developed by combining a dual network hydrogel of oxidized glucomannan aldehyde (KGM-CHO) and levodopa-grafted ε-polylysine (EPL-DOPA). The “cytokine reservoir” hydrogel actively recruited macrophages through electrostatic forces and regulated macrophages by mimicking “receptor-ligand” interactions to alter cytokine production patterns. Meanwhile, the dual network hydrogels recruited and stored cytokines by “charge” force then released them according to the degradation of hydrogels, leading to the change of cytokine release pattern. In conclusion, this study provided a unique insight in designing the cytokine management-based tissue engineering strategies for tissue repair.
The red blood cell (RBC) deformability is a critical aspect, and assessing the cell deformation characteristics is essential for better diagnostics of healthy and deteriorating RBCs. There is a need to explore the connection between the cell deformation characteristics, cell morphology, disease states, storage lesion and cell shape-transformation conditions for better diagnostics and treatments. A numerical approach inspired from the previous research for RBC morphology predictions and for analysis of RBC deformations is proposed for the first time, to investigate the deformation characteristics of different RBC morphologies. The present study investigates the deformability characteristics of stomatocyte, discocyte and echinocyte morphologies during optical tweezers stretching and provides the opportunity to study the combined contribution of cytoskeletal spectrin network and the lipid-bilayer during RBC deformation. The proposed numerical approach predicts agreeable deformation characteristics of the healthy discocyte with the analogous experimental observations and is extended to further investigate the deformation characteristics of stomatocyte and echinocyte morphologies. In particular, the computer simulations are performed to investigate the influence of direct stretching forces on different equilibrium cell morphologies on cell spectrin link extensions and cell elongation index, along with a parametric analysis on membrane shear modulus, spectrin link extensibility, bending modulus and RBC membrane–bead contact diameter. The results agree with the experimentally observed stiffer nature of stomatocyte and echinocyte with respect to a healthy discocyte at experimentally determined membrane characteristics and suggest the preservation of relevant morphological characteristics, changes in spectrin link densities and the primary contribution of cytoskeletal spectrin network on deformation behaviour of stomatocyte, discocyte and echinocyte morphologies during optical tweezers stretching deformation. The numerical approach presented here forms the foundation for investigations into deformation characteristics and recoverability of RBCs undergoing storage lesion.
Traumatic peripheral nerve injury represents a major clinical and public health problem that often leads to significant functional impairment and permanent disability. Despite modern diagnostic procedures and advanced microsurgical techniques, functional recovery after peripheral nerve repair is often unsatisfactory. Therefore, there is an unmet need for new therapeutic or adjunctive strategies to promote the functional recovery in nerve injury patients. In contrast to the central nervous system, Schwann cells in the peripheral nervous system play a pivotal role in several aspects of nerve repair such as degeneration, remyelination, and axonal growth. Several non‐surgical approaches, including pharmacological, electrical, cell‐based, and laser therapies, have been employed to promote myelination and enhance functional recovery after peripheral nerve injury. This review will succinctly discuss the potential therapeutic strategies in the context of myelination following peripheral neurotrauma.
The outcome of management of diabetic foot ulcers remains a challenge, and there remains continuing uncertainty concerning optimal approaches to management. It is for these reasons that in 2008 and 2012, the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing published systematic reviews of the evidence to inform protocols for routine care and to highlight areas, which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between June 2010 and June 2014. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following ten categories: sharp debridement and wound bed preparation with larvae or hydrother-apy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; oxygen and other gases, compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, electromagnetic, lasers, shockwaves and ultrasound and other systemic therapies, which did not fit in the aforementioned categories. Heterogeneity of studies prevented pooled analysis of results. Of the 2161 papers identified, 30 were selected for grading following full text review. The present report is an update of the earlier IWGDF systematic reviews, and the conclusion is similar: that with the possible exception of negative pressure wound therapy in post-operative wounds, there is little published evidence to justify the use of newer therapies. Analysis of the evidence continues to present difficulties in this field as controlled studies remain few and the majority continue to be of poor methodological quality.
Proper control of cell migration is critically important in many biologic processes, such as wound healing, immune surveillance, and development. Much progress has been made in the initiation of cell migration; however, little is known about termination and sometimes directional reversal. During active cell migration, as in wound healing, development, and immune surveillance, the integrin expression profile undergoes drastic changes. Here, we uncovered the extensive regulatory and even opposing roles of integrins in directional cell migration in electric fields (EFs), a potentially important endogenous guidance mechanism. We established cell lines that stably express specific integrins and determined their responses to applied EFs with a high throughput screen. Expression of specific integrins drove cells to migrate to the cathode or to the anode or to lose migration direction. Cells expressing αMβ2, β1, α2, αIIbβ3, and α5 migrated to the cathode, whereas cells expressing β3, α6, and α9 migrated to the anode. Cells expressing α4, αV, and α6β4 lost directional electrotaxis. Manipulation of α9 molecules, one of the molecular directional switches, suggested that the intracellular domain is critical for the directional reversal. These data revealed an unreported role for integrins in controlling stop, go, and reversal activity of directional migration of mammalian cells in EFs, which might ensure that cells reach their final destination with well‐controlled speed and direction.—Zhu, K., Takada, Y., Nakajima, K., Sun, Y., Jiang, J., Zhang, Y., Zeng, Q., Takada, Y., Zhao, M. Expression of integrins to control migration direction of electrotaxis. FASEB J. 33, 9131–9141 (2019). www.fasebj.org
Endogenous wound electric fields (EFs), an important and fundamental occurrence of wound healing, profoundly influence the directed migration of keratinocytes. Although numerous studies have unveiled the signals responsible for EF‐biased direction, the mechanisms by which EFs promote keratinocyte motility remains to be elucidated. In our study, EFs enhanced the directed migratory speed of keratinocytes by inducing autophagic activity, thereby facilitating skin barrier restoration. Initially, we found that electrical signals directed keratinocytes to the cathode with enhanced motility parameters [i.e., trajectory distance, trajectory speed, displacement distance, and displacement speed (Td/t)] and more efficient migration (directionality and Td/t along the x axis, among others). Meanwhile, EFs induced a time‐dependent increase in autophagic activity in keratinocytes, with constant autophagic flux, accompanied by increased transcription of numerous autophagy‐related genes. Deficiency in Atg5, a key protein necessary for autophagosome formation, led to significant reduction of autophagy, which was accompanied by a substantial reduction in EF‐stimulated directed motility. These results demonstrated a causal relationship between autophagy and EF‐directed migratory speed. In addition, both cell migration under normal conditions and EF‐biased directionality were autophagy independent. Thus, our findings define autophagy as an important functional regulator of electrically enhanced directed motility, adding to a growing understanding of EFs.—Yan, T., Jiang, X., Lin, G., Tang, D., Zhang, J., Guo, X., Zhang, D., Zhang, Q., Jia, J., Huang, Y. Autophagy is required for the directed motility of keratinocytes driven by electric fields. FASEB J. 33, 3922–3935 (2019). www.fasebj.org
Skin wound healing is a major health care issue. While electric stimulations have been known for decades to be effective for facilitating skin wound recovery, practical applications are still largely limited by the clumsy electrical systems. Here, we report an efficient electrical bandage for accelerated skin wound healing. On the bandage, an alternating discrete electric field is generated by a wearable nanogenerator by converting mechanical displacement from skin movements into electricity. Rat studies demonstrated rapid closure of a full-thickness rectangular skin wound within 3 days as compared to 12 days of usual contraction-based healing processes in rodents. From in vitro studies, the accelerated skin wound healing was attributed to electric field-facilitated fibroblast migration, proliferation, and transdifferentiation. This self-powered electric-dressing modality could lead to a facile therapeutic strategy for nonhealing skin wound treatment.
[This corrects the article DOI: 10.1371/journal.pone.0191074.].
Electrical stimulation induces significant neovessel formation in vivo We have shown that electrical stimulation of endothelial cells functions as an important contributor to angiogenesis in monolayer culture. Because angiogenesis occurs in a three-dimensional (3D) environment, in this study we investigated the effects of a direct current (DC) electrical field (EF) on endothelial neovessel formation in 3D culture. There was a significant increase in tube formation when endothelial cells were stimulated with EF for 4 h. The lengths of the tube-like structures were augmented further by the continued EF exposure. The lengths of the tubes also increased dose-dependently in the EF-treated cultures in the field strengths of 50 mV/mm∼200 mV/mm for 6 h. Electrical fields of small physiological magnitude enhanced VEGF expression by endothelial cells in 3D culture. EF treatment also resulted in activation of VEGFR2, Akt, extracellular regulated kinase 1,2 (Erk1/2), as well as the c-Jun NH2-terminal kinase (JNK). The tyrosine kinase inhibitor SU1498 that blocks VEGFR2 activity exhibited a potent inhibition of tube growth, and the Akt inhibitor MK-2206 2HCl, the Erk1/2 inhibitor U0126 and the JNK inhibitor SB203580 significantly reduced EF-stimulated tubulogenesis. These results suggest the importance of the VEGFR2 signaling pathway during EF-induced angiogenesis. The results of this study provide novel evidence that endogenous EFs may promote blood vessel formation of endothelial cells by activating the VEGF receptor signaling pathway.
During wound healing, cells migrate with electrotactic bias as a collective entity. Unlike the case of EF-induced single cell migration, the sensitivity of electrotactic response depends primarily on the integrity of the cell-cell junctions in the monolayer. Although there exist biochemical clues on how cells sense EF, well-defined physical portrait to illustrate how collective cells respond to directional EF remains elusive. Here, we developed an EF stimulating system integrated with a hydrogel-based traction measurement platform to quantify the EF-induced changes in cellular tractions, from which the complete in-plane intercellular stress tensor can be calculated. We chose immortalized human keratinocyte, HaCaT, as our model cells to elucidate the role of electric field in epithelial migration during wound healing. With the onset of 0.5 V/cm EF, HaCaT monolayer immediately migrated toward anode with ordered directedness and enhanced speed as early as 15mins. Cellular traction and intercellular stresses were aligned perpendicular to the direction of EF within 30mins. The EF-induced reorientation of physical stresses was then followed by the lagged cell body reorientation in the direction perpendicular to the EF. Once the intercellular stresses were aligned, the reversal of the EF direction induced the reversed migration of the cells without any apparent disruption of the intercellular stress, suggesting that the dislodging of the physical stress alignment along the adjacent cells not be necessary for changing the direction of monolayer migration. Movie S1 Movie S1 Collective HaCaT migration in the absence of EF stimulation. Movie S2 Movie S2 Collective HaCaT migration with the onset of EF stimulation. (Anode on top, cathode at the bottom) Movie S3 Movie S3 Redirecting migration of HaCaT monolayer during the EF direction reversal. (New anode at the bottom, new cathode on top).
Erythrocytes must maintain a biconcave discoid shape in order to efficiently deliver oxygen (O2 ) molecules and to recycle carbon dioxide (CO2 ) molecules. The erythrocyte is a small toroidal dielectrophoretic (DEP) electromagnetic field (EMF) driven cell that maintains its zeta potential (ζ) with a dielectric constant (ԑ) between a negatively charged plasma membrane surface and the positively charged adjacent Stern layer. Here, we propose that zeta potential is also driven by both ferroelectric influences (chloride ion) and ferromagnetic influences (serum iron driven). The Golden Ratio, a function of Phi φ, offers a geometrical mathematical measure within the distinct and desired curvature of the red blood cell that is governed by this zeta potential and is required for the efficient recycling of CO2 in our bodies. The Bio-Field Array (BFA) shows potential to both drive/fuel the zeta potential and restore the Golden Ratio in human erythrocytes thereby leading to more efficient recycling of CO2 . Live Blood Analyses and serum CO2 levels from twenty human subjects that participated in immersion therapy sessions with the BFA for 2 weeks (six sessions) were analyzed. Live Blood Analyses (LBA) and serum blood analyses performed before and after the BFA immersion therapy sessions in the BFA pilot study participants showed reversal of erythrocyte rheological alterations (per RBC metric; P = 0.00000075), a morphological return to the Golden Ratio and a significant decrease in serum CO2 (P = 0.017) in these participants. Immersion therapy sessions with the BFA show potential to modulate zeta potential, restore this newly defined Golden Ratio and reduce rheological alterations in human erythrocytes.
Objective:
This review focusses on the erythrocytes (RBCs) and their structural changes during inflammation and impaired blood rheology. We discuss systemic inflammation and the effects of dysregulated inflammatory molecules. These pro-inflammatory molecules directly affect the haematological system, and particularly the RBCs, platelets and plasma proteins. We focus on the three main changes; increased RBC eryptosis (programmed cell death, similar to apoptosis) and pathological deformability, platelet hyperreactivity and anomalous blood clotting, due to pathological changes to fibrin(ogen) protein structure. This pro-inflammatory haematological system directly affects blood rheology. In turn, hemorheological parameters such as RBC deformability are important parameters in hypercoagulation, which is a hallmark of inflammation. For RBC deformation to happen during blood flow, the RBC membrane needs to be elastic to elongate sufficiently to squeeze through small capillaries. However, of greater importance is that the cell must return to its original biconcave shape after exiting the small diameter capillaries.
Conclusion:
Hemorheological parameters such as RBC deformability are of great importance clinically, to both identify the presence and extent of inflammation, and to study these parameters during intervention therapies. RBC rheology and deformability may therefore be a useful cell model for pharmaceutical testing.
Introduction:
Severe burns benefit from skin grafting, and grafting surgery is of great importance in the treatment of these injuries. As a result, there is formation of an additional wound at the donor site, which is painful and susceptible to infection. However, the therapeutic approach to these problems at donor sites for skin grafting is insufficiently explored in the literature.
Aim:
To evaluate electrical stimulation of the donor sites of burn patients treated by grafting surgery.
Methods:
This work evaluated 30 donor sites of cutaneous graft burn patients treated with high-voltage electrical stimulation. Subjects were randomized into two groups: electrical stimulation (GES), treated with electrostimulation (50min, 100Hz, twin pulses 15 us, monophasic), and the sham group (GS), treated by the same procedures but without current. Pain was assessed by visual analog scale daily before and after the electrical stimulation. The time elapsed until complete epithelization was evaluated (time of primary dressing detached spontaneously). Skin temperature was measured by thermography. The characteristics of donor sites were qualitatively evaluated using images and the plug-in CaPAS® (Carotid Plaque Analysis Software).
Results:
The results showed a significant decrease in pain, which was absent on the third day in the GES and the sixth day in the GS. The time the primary dressing detached spontaneously in days decreased (p<0.05) (4.7±0.2) compared to the GS group (7.0±1.3). Donor site healing characteristics such as vascularization, pigmentation, height, the quantity of crust formed, irregularities, and the quality of healing was better in the GES; moreover, homogeneity and inertia of the images confirmed higher healing quality.
Conclusion:
As a result of the study, the technology shows promise and merits a larger study with objective assessments and different physical variables.
Skin graft is a standard therapeutic technique in patients with deep ulcers, but managing donor site after grafting is very important. Although several modern dressings are available to enhance the comfort of donor site, using techniques that accelerate wound healing may enhance patient satisfaction. Low-level laser therapy (LLLT) has been used in several medical fields, including healing of diabetic, surgical, and pressure ulcers, but there is not any report of using this method for healing of donor site in burn patients. The protocols and informed consent were reviewed according to Medical Ethics Board of Shahid Beheshti University of Medical Sciences (IR.SBMU.REC.1394.363) and Iranian Registry of Clinical Trials (IRCT2016020226069N2). Eighteen donor sites in 11 patients with grade 3 burn ulcer were selected. Donor areas were divided into 2 parts, for laser irradiation and control randomly. Laser area was irradiated by a red, 655-nm laser light, 150 mW, 2 J/cm², on days 0 (immediately after surgery), 3, 5, and 7. Dressing and other therapeutic care for both sites were the same. The patients and the person who analyzed the results were blinded. The size of donor site reduced in both groups during the 7-day study period (P < 0.01) and this reduction was significantly greater in the laser group (P = 0.01). In the present study, for the first time, we evaluate the effects of LLLT on the healing process of donor site in burn patients. The results showed that local irradiation of red laser accelerates wound healing process significantly.
The present study investigated the effects of pulsed electromagnetic field (PEMF) on the tensile biomechanical properties of diabetic wounds at different phases of healing. Two intensities of PEMF were adopted for comparison.
We randomly assigned 111 10-week-old male streptozotocin-induced diabetic Sprague-Dawley rats to two PEMF groups and a sham control group. Six-millimetre biopsy punched full thickness wounds were made on the lateral side of their hindlimbs. The PEMF groups received active PEMF delivered at 25 Hz with intensity of either 2 mT or 10 mT daily, while the sham group was handled in a similar way except they were not exposed to PEMF. Wound tissues were harvested for tensile testing on post-wounding days 3, 5, 7, 10, 14 and 21. Maximum load, maximum stress, energy absorption capacity, Young’s modulus and thickness of wound tissue were measured.
On post-wounding day 5, the PEMF group that received 10-mT intensity had significantly increased energy absorption capacity and showed an apparent increase in the maximum load. However, the 10-mT PEMF group demonstrated a decrease in Young’s modulus on day 14. The 10-mT PEMF groups showed a significant increase in the overall thickness of wound tissue whereas the 2-mT group showed a significant decrease in the overall maximum stress of the wounds tissue.
The present findings demonstrated that the PEMF delivered at 10 mT can improve energy absorption capacity of diabetic wounds in the early healing phase. However, PEMF (both 2-mT and 10-mT) seemed to impair the material properties (maximum stress and Young’s modulus) in the remodelling phase. PEMF may be a useful treatment for promoting the recovery of structural properties (maximum load and energy absorption capacity), but it might not be applied at the remodelling phase to avoid impairing the recovery of material properties.
The study of the effects of low-level laser (LLL) radiation on blood is important for elucidating the mechanisms behind the interaction of LLL radiation and biologic tissues. Different therapy methods that involve blood irradiation have been developed and used for clinical purposes with beneficial effects. The aim of this study was to compare the effects of different irradiation protocols using a diode-pumped solid-state LLL (λ = 405 nm) on samples of human blood by measuring the erythrocyte sedimentation rate (ESR). Human blood samples were obtained through venipuncture into tubes containing EDTA as an anticoagulant. Every sample was divided into two equal aliquots to be used as an irradiated sample and a non-irradiated control sample. The irradiated aliquot was subjected to a laser beam with a wavelength of 405 nm and an energy density of 72 J/cm2. The radiation source had a fixed irradiance of 30 mW/cm2. The ESR change was observed for three different experimental protocols: irradiated whole blood, irradiated red blood cells (RBCs) samples re-suspended in non-irradiated blood plasma, and non-irradiated RBCs re-suspended in irradiated blood plasma. The ESR values were measured after laser irradiation and compared with the non-irradiated control samples. Irradiated blood plasma in which non-radiated RBCs were re-suspended was found to result in the largest ESR decrease for healthy human RBCs, 51%, when compared with RBCs re-suspended in non-irradiated blood plasma. The decrease in ESR induced by LLL irradiation of the plasma alone was likely related to changes in the plasma composition and an increase in the erythrocyte zeta potential upon re-suspension of the RBCs in the irradiated blood plasma.
Collective cell migration is important in various physiological processes such as morphogenesis, cancer metastasis and cell regeneration. Such migration can be induced and guided by different chemical and physical cues. Electrotaxis, referring to the directional migration of adherent cells under stimulus of electric fields, is believed to be highly involved in the wound-healing process. Electrotactic experiments are conventionally conducted in Petri dishes or cover glasses wherein cells are cultured and electric fields are applied. However, these devices suffer from evaporation of the culture medium, non-uniformity of electric fields and low throughput. To overcome these drawbacks, micro-fabricated devices composed of micro-channels and fluidic components have lately been applied to electrotactic studies. Microfluidic devices are capable of providing cells with a precise micro-environment including pH, nutrition, temperature and various stimuli. Therefore, with the advantages of reduced cell/reagent consumption, reduced Joule heating and uniform and precise electric fields, microfluidic chips are perfect platforms for observing cell migration under applied electric fields. In this paper, I review recent developments in designing and fabricating microfluidic devices for studying electrotaxis, aiming to provide critical updates in this rapidly-growing, interdisciplinary field.
New developments in accelerating wound healing can have immense beneficial socioeconomic impact. The wound healing process is a highly orchestrated series of mechanisms where a multitude of cells and biological cascades are involved. The skin battery and current of injury mechanisms have become topics of interest for their influence in chronic wounds. Electrostimulation therapy of wounds has shown to be a promising treatment option with no-device-related adverse effects. This review presents an overview of the understanding and use of applied electrical current in various aspects of wound healing. Rapid clinical translation of the evolving understanding of biomolecular mechanisms underlying the effects of electrical simulation on wound healing would positively impact upon enhancing patient’s quality of life.
The purpose of this study is to investigate the effect of pulsed electrical field (PEF) and photobiomodulation laser (PBM) on the viability of the TRAM flap in diabetic rats. Fifty Wistar rats were divided into five homogeneous groups: Group 1—control; Group 2—diabetics; Group 3—diabetics + PEF; Group 4—diabetic + laser 660 nm, 10 J/cm2, 0.27 J; Group 5—diabetic + laser 660 nm, 140 J/cm2, 3.9 J. The percentage of necrotic area was evaluated using software Image J®. The peripheral circulation of the flap was evaluated by infrared thermography FLIR T450sc (FLIR® Systems—Oregon USA). The thickness of the epidermis (haematoxylin-eosin), mast cell (toluidine blue), leukocytes, vascular endothelial growth factor, fibroblast and newly formed blood vessels were evaluated. For the statistical analysis, the Kruskal-Wallis test was applied followed by Dunn and ANOVA test followed by Tukey with critical level of 5% (p < 0.05). The PEF reduced the area of necrosis, decreased the leukocytes, increased the mast cells, increased the thickness of epidermis and increased newly formed blood vessels when it was compared to the untreated diabetic group of animals. Laser 660 nm, fluence 140 J/cm2 (3.9 J) showed better results than the 10 J/cm2 (0.27 J) related to reduction of the area of necrosis and the number of leukocytes, increased mast cells, increased thickness of the epidermis, increased vascular endothelial growth factor, increased fibroblast growth factor and increase of newly formed blood vessels in diabetic animals. The laser and pulsed electrical field increase the viability of the musculocutaneous flap in diabetic rats.
The aim of this study was to evaluate the effects of low-level laser therapy (LLT) in pressure ulcers (PU) in humans through a systematic review of randomized studies. The search includes the databases MEDLINE, PEDro, Cochrane CENTRAL, and Lilacs, as well a manual search until May, 2016. This included randomized clinical trials of LLT compared with other interventions, different types of LLT, LLT placebo, or control in the treatment of PU. The outcomes evaluated were the ulcer area, healing rate, and overall healing rate. The risk of bias was evaluated using the tool of the Cochrane Collaboration, and the results were analyzed descriptively. From the 386 articles identified, only four studies were included, with two LLT used with single wavelength (1: 904 nm vs. control and 2: 940 nm vs. 808 nm vs. 658 nm vs. placebo) and two LLT used to probe cluster. One study compared to different single wavelengths showed a significant 71% reduction of the PU and an improved healing rate in which 47% of PU healed completely after 1 month of therapy with the use of LLT with a wavelength of 658 nm compared with other lengths. The other analyzed wavelengths were not significant in the assessed outcomes. Significant results were observed in the use of LLT with a 658 nm wavelength, and no evidence was found for use of wavelengths above that for the treatment of PU. Therefore, we also found no evidence in the laser used to probe the cluster.
Registration number: CRD42016036648.
The aim of this study was to investigate the effect of laser photobiomodulation (PBM) on the viability of the transverse rectus abdominis musculocutaneous (TRAM) flap in rats subjected to the action of nicotine. We evaluated 60 albino Wistar rats, divided into six groups of ten animals. Group 1 (saline) underwent the surgical technique to obtain a TRAM flap; group 2 (laser 830 nm) underwent the surgical technique and was irradiated with a laser 830 nm; group 3 (laser 660 nm) underwent the surgical technique and was irradiated with a laser 660 nm; group 4 was treated with nicotine subcutaneously (2 mg/kg/2×/day/4 weeks) and underwent surgery; group 5 (nicotine + laser 830 nm) was exposed to nicotine, underwent the surgical technique, and was irradiated with a laser 830 nm; group 6 (nicotine + laser 660 nm) was exposed to nicotine, underwent the surgical technique, and was irradiated with a laser 660 nm. The application of PBM occurred immediately after surgery and on the two following days. The percentage of necrosis was assessed using the AxioVision® software. The number of mast cells (toluidine blue staining) was evaluated, and immunohistochemistry was performed to detect vascular endothelial growth factor expression (anti-VEGF-A), fibroblasts (anti-basic FGF), and neoformed vessels (anti-CD34). PBM with a wavelength of 830 nm increased the viability of the TRAM flap, with a smaller area of necrosis, increased number of mast cells, and higher expression of VEGF and CD34. PBM increases the viability of musculocutaneous flaps treated with to nicotine.
Chronic wounds represent a significant burden to health services and are associated with patient morbidity. Novel methods to diagnose and/or treat problematic wounds are needed. Interleukin (IL)-15 is a cytokine involved in a number of biological processes and disease states such as inflammation, healing and cancer progression. The current study explores the expression profile of IL-15 and IL-15 receptor α (IL-15Rα) in chronic wounds and its impact on keratinocytes. IL-15 and IL-15Rα expression were examined in healing and non-healing chronic wounds using qPCR and immunohistochemical analysis. The impact of recombinant IL-15 (rhIL-15) on human adult low calcium temperature (HaCaT) keratinocyte growth and migratory potential was further examined. IL-15 transcript expression was slightly, though non-significantly elevated in healing chronic wounds compared with non-healing chronic wounds. IL-15 protein staining was minimal in both subtypes of chronic wounds. By contrast, IL-15Rα transcript and protein expression were both observed to be enhanced in non-healing chronic wounds compared with healing chronic wounds. The treatment of HaCaT cells with rhIL-15 generally enhanced cell growth and promoted migration. Analysis with small molecule inhibitors suggested that the pro-migratory effect of rhIL-15 may be associated with ERK, AKT, PLCγ and FAK signalling. IL-15 may promote healing traits in keratinocytes and the differential expression of IL-15Rα is observed in chronic wounds. Together, this may imply a complex role for this interleukin in wound healing.
Laser biostimulation in medicine has become widespread supporting the idea of therapeutic effects of photobiomodulation in biological tissues. The aim of this study was to investigate the biostimulation effect of laser irradiation on healing of cutaneous skin wounds, in vivo, by means of bioimpedance measurements and histological examinations. Cutaneous skin wounds on rats were subjected to 635 nm diode laser irradiations at two energy densities of 1 and 3 J/cm2 separately. Changes in the electrical properties of the wound sites were examined with multi-frequency electrical impedance measurements performed on the 3rd, 7th, 10th, and 14th days following the wounding. Tissue samples were both morphologically and histologically examined to determine the relationship between electrical properties and structure of tissues during healing. Laser irradiations of both energy densities stimulated the wound healing process. In particular, laser irradiation of lower energy density had more evidence especially for the first days of healing process. On the 7th day of healing, 3 J/cm2 laser-irradiated tissues had significantly smaller wound areas compared to non-irradiated wounds (p < 0.05). The electrical impedance results supported the idea of laser biostimulation on healing of cutaneous skin wounds. Thus, bioimpedance measurements may be considered as a non-invasive supplementary method for following the healing process of laser-irradiated tissues.
Macrophages are key cells in inflammation and repair, and their activity requires close regulation. The characterization of cues coordinating macrophage function has focused on biologic and soluble mediators, with little known about their responses to physical stimuli, such as the electrical fields that are generated naturally in injured tissue and which accelerate wound healing. To address this gap in understanding, we tested how properties of human monocyte-derived macrophages are regulated by applied electrical fields, similar in strengths to those established naturally. With the use of live-cell video microscopy, we show that macrophage migration is directed anodally by electrical fields as low as 5 mV/mm and is electrical field strength dependent, with effects peaking ∼300 mV/mm. Monocytes, as macrophage precursors, migrate in the opposite, cathodal direction. Strikingly, we show for the first time that electrical fields significantly enhance macrophage phagocytic uptake of a variety of targets, including carboxylate beads, apoptotic neutrophils, and the nominal opportunist pathogen Candida albicans, which engage different classes of surface receptors. These electrical field-induced functional changes are accompanied by clustering of phagocytic receptors, enhanced PI3K and ERK activation, mobilization of intracellular calcium, and actin polarization. Electrical fields also modulate cytokine production selectively and can augment some effects of conventional polarizing stimuli on cytokine secretion. Taken together, electrical signals have been identified as major contributors to the coordination and regulation of important human macrophage functions, including those essential for microbial clearance and healing. Our results open up a new area of research into effects of naturally occurring and clinically applied electrical fields in conditions where macrophage activity is critical.
Objective: Optical microangiography (OMAG)-based optical coherence tomography is a noninvasive technique capable of imaging functional microvasculature innervating scanned tissue volume. In this study, we utilize OMAG to investigate dynamic changes of microcirculation during the healing process of a burn. Approach: A soft-contact superficial burn injury was induced on a mouse ear with 1 μL 70°C hot water. Microangiograms were generated by using OMAG before and after the burn. Results: Vessel recruitment and remodeling were observed in the healing process. Burn injury reached to the worst extent within the first 24 h and had no expansion thereafter. The interrupted microcirculation in the mouse ear was progressively recovered in the consequent postburn days and completely healed on postburn day 7. Innovation: OMAG provides a novel way for noninvasive visualization and quantification of vasculature changes over time after burn injuries. The high resolution achieved by the imaging system reveals microvascular details down to capillary level. Conclusion: Our results demonstrated that OMAG has great potential to improve the understanding of microcirculatory responses to burns and thus benefit the development of effective therapeutics.
Background:
In microcirculation, the non-Newtonian behavior of blood and the complexity of the microvessel network are responsible for the high flow resistance and the large reduction of the blood pressure. Red blood cell aggregation along with inward radial migration are two significant mechanisms determining the former. Yet, their impact on hemodynamics in non-straight vessels is not well understood.
Objective:
In this study, the steady state blood flow in stenotic rigid vessels is examined, employing a sophisticated non-homogeneous constitutive law. The effect of red blood cells migration on the hydrodynamics is quantified and the constitutive model's accuracy is evaluated.
Methods:
A numerical algorithm based on the two-dimensional mixed finite element method and the EVSS/SUPG technique for a stable discretization of the mass and momentum conservation equations in addition to the constitutive model is employed.
Results:
The numerical simulations show that a cell-depleted layer develops along the vessel wall with an almost constant thickness for slow flow conditions. This causes the reduction of the drag force and the increase of the pressure gradient as the constriction ratio decreases.
Conclusions:
Viscoelastic effects in blood flow were found to be responsible for steeper decreases of tube and discharge hematocrits as decreasing function of constriction ratio.
Peripheral nerve injury afflicts individuals from all walks of life. Despite the peripheral nervous system's intrinsic ability to regenerate, many patients experience incomplete functional recovery. Surgical repair aims to expedite this recovery process in the most thorough manner possible. However, full recovery is still rarely seen especially when nerve injury is compounded with polytrauma where surgical repair is delayed. Pharmaceutical strategies supplementary to nerve microsurgery have been investigated but surgery remains the only viable option. Brief low-frequency electrical stimulation of the proximal nerve stump after primary repair has been widely investigated. This article aims to review the currently known biological basis for the regenerative effects of acute brief low-frequency electrical stimulation on axonal regeneration and outline the recent clinical applications of the electrical stimulation protocol to demonstrate the significant translational potential of this modality for repairing peripheral nerve injuries. The review concludes with a discussion of emerging new advancements in this exciting area of research. The current literature indicates the imminent clinical applicability of acute brief low-frequency electrical stimulation after surgical repair to effectively promote axonal regeneration as the stimulation has yielded promising evidence to maximize functional recovery in diverse types of peripheral nerve injuries.
Central and peripheral nerve injuries pose a great threat to people. Complications such as inflammation, muscle atrophy, traumatic neuromas and delayed reinnervation can bring huge challenges to clinical practices and barriers to complete nerve regrowth. Physical interventions such as electrical and magnetic stimulation show satisfactory results with varying parameters for acute and chronic nerve damages. The biological basis of electrical and magnetic stimulation mainly relies on protein synthesis, ion channel regulation and growth factor secretion. This review focuses on the various paradigms used in different models of electrical and magnetic stimulation and their regenerative potentials and underlying mechanisms in nerve injuries. The combination of physical stimulation and conductive biomaterial scaffolds displays an infinite potentiality in translational application in nerve regeneration.
Background and objectives:
Photobiomodulation (PBM) therapy with 830 nm wavelength or 660 wavelength to compare the effects with parameters of 30 mW, 0.028 cm2 , 9.34 seconds, and 3.64 J on the total integration of total skin grafts in rats submitted to nicotine.
Study design/materials and methods:
Sixty male Wistar rats were divided in six groups: Sham-skin-grafting surgery; 830 nm-skin-grafting followed by 830 nm irradiation; 660 nm-skin grafting followed by 660 nm irradiation; Nicotine-subjected to subcutaneous nicotine injection (2 mg/kg twice a day for 4 weeks), followed by skin grafting; Group Nicotine/830 nm-similar to Group Nicotine, followed by 830 nm irradiation; Group Nicotine/660 nm-similar to Group Nicotine, followed by 660 nm irradiation. The percentage contraction of the grafting tissue was evaluated through ImageJ®. The thickness of the epidermis, inflammatory infiltrates, and the space between the implanted tissue and receptor bed were determined by histology; and the expression of vascular growth factor and blood vessel density (factor VIII) were evaluated by immunohistochemistry.
Results:
The PBM at both wavelengths promoted a facilitating effect on the integration of the skin graft under nicotine and had a more significant effect on the thickness of the epidermis and expression of angiogenesis without nicotine at a wavelength of 830 nm. Different wavelengths influence responses related to the viability of cutaneous grafts in rats submitted to nicotine.
Conclusions:
The PBM with 830 nm and 660 nm promoted beneficial results in skin grafts submitted to the deleterious action of nicotine. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Endogenous electric fields (EFs) direct the migration (electrotaxis) of keratinocytes in skin wounds, and the exogenous application of EFs may therefore improve wound healing, but the potential benefits are limited by the side effects of constant direct current (DC) passing through tissues. In contrast, with pulsed DC (characterized by intermittent output), parameters can be adjusted to minimize the adverse effects of electric currents. However, it remains unknown whether pulsed DC can reliably induce keratinocyte electrotaxis. In this study, using primary keratinocytes in an electrotaxis chamber, we found that a pulsed DCEF at physiological strength (EF = 150 mV/mm, duty cycle = 60%, frequency = 0.1 Hz) could induce robust electrotaxis. This effect was dependent on both voltage and duty cycle, but not on frequency. As predicted, fewer electrochemical reactions and cytotoxic reactions were detected with pulsed DCEF than with constant DCEF. In summary, we here demonstrate for the first time, that pulsed DCEF can trigger keratinocyte electrotaxis comparable to that induced by constant DCEF, while minimizing the electrochemical side effects. These findings support the future development of a pulsed DCEF device to improve wound healing in human patients.
Electric fields are among physical stimuli that have revolutionized therapy. Occurring endogenously or exogenously, the electric field can be used as a trigger for controlled drug release from electroresponsive drug delivery systems, can stimulate wound healing and cell proliferation, may enhance endocytosis or guide stem cell differentiation. Electric field pulses may be applied to induce cell fusion, can increase the penetration of therapeutic agents into cells, or can be applied as a standalone therapy to ablate tumors. This review describes the main therapeutic trends and overviews the main physical, chemical and biological mechanisms underlying the actions of electric fields. Overall, the electric field can be used in therapeutic approaches in several ways. The electric field can act on drug carriers, cells and tissues. Understanding the multiple effects of this powerful tool will help harnessing its full therapeutic potential in an efficient and safe way.
This review was conducted to determine and quantify the efficacy of high-voltage monophasic pulsed current (HVMPC) in the treatment of stage II-IV pressure ulcers (PrUs), identify the details of HVMPC intervention parameters and the superior protocol, and ascertain other potential benefits and the safety of HVMPC intervention. Eleven studies, nine randomized controlled trials (RCTs) and two case series studies, matched the criteria and were included in the systematic review, whereas, only level 1 evidence RCTs were included in the meta-analysis. The percentage of wound surface area reduction per week was 12.39%; 95% CI, [10.43-14.37] for HVMPC plus standard wound care (SWC) and 6.96%; 95% CI, [5.56-8.38] for SWC alone or SWC plus sham HVMPC. The net effect of HVMPC was 5.4% per week (an increase of 78% greater than SWC alone or SWC plus sham HVMPC). Level 1, 2 and 4 evidence studies have consistently indicated that HVMPC plus SWC were more effective than SWC alone or SWC plus sham HVMPC in treating stage II-IV PrUs. Level 1 evidence studies showed that HVMPC intervention improved the healing of PrUs (reduced wound surface area), and combined with SWC, increased the probability of complete healing and almost eliminated the probability of worsening of healing. HVMPC intervention was shown to be relatively safe, with rare adverse reactions.
It is well documented that physiological electric fields provide the earliest signals necessary to initiate cell proliferation, migration, and ultimately re-epithelialization of wounds. Additionally, electricity is known to exert an antimicrobial effect. An electric field-generating wound dressing designed to mimic physiological electric fields has not been described in the small animal clinic. This manuscript retrospectively reviews the use of a microcell battery-impregnated bioelectric dressing (BED) in five small animal patients with complex wounds. For each patient, product application and wound healing progress was monitored and documented over several weeks. Despite the severity of the wounds and being at high risk for infection, all presenting wounds treated with BED achieved complete closure within 4 weeks without becoming infected or requiring grafting. These cases provide early evidence that use of the BED is feasible in a small animal clinic and may support healing while providing topical, non-antibiotic activity against wound pathogens.
Voltages across various glabrous (and gland-free) regions of cavy skin range from 30 to 100 mV, inside positive; across hairy ones, 0 to 10 mV. (moreover, hairy areas also tend to maintain lower transcutaneous voltages in man.) When an incision is made through the glabrous epidermis of the cavy, a microampere flows through each millimeter of the cut's edge. These wound currents generate lateral, intraepidermal voltage gradients or fields of about 100-200 mV/mm near the cut; fields which decline with distance from the cut with a space constant of 0.3-0.4 mm. It is deduced from these data that the epidermis near a cut drives up to 300 microA/cm2 across itself; moreover, these currents and potentials can be grossly, rapidly, and (to some extent) reversibly reduced by amiloride. It is concluded that the hair and gland-free skin of cavies has a battery comparable in power and character to that of frogs; but it is suggested that this mammalian battery may primarily subserve epidermal wound healing rather than salt uptake.
Objective:
This study was designed to employ electroceutical principles, as an alternative to pharmacological intervention, to manage wound biofilm infection. Mechanism of action of a United States Food and Drug Administration-cleared wireless electroceutical dressing (WED) was tested in an established porcine chronic wound polymicrobial biofilm infection model involving inoculation with Pseudomonas aeruginosa PAO1 and Acinetobacter baumannii 19606.
Background:
Bacterial biofilms represent a major wound complication. Resistance of biofilm toward pharmacologic interventions calls for alternative therapeutic strategies. Weak electric field has anti-biofilm properties. We have previously reported the development of WED involving patterned deposition of Ag and Zn on fabric. When moistened, WED generates a weak electric field without any external power supply and can be used as any other disposable dressing.
Methods:
WED dressing was applied within 2 hours of wound infection to test its ability to prevent biofilm formation. Alternatively, WED was applied after 7 days of infection to study disruption of established biofilm. Wounds were treated with placebo dressing or WED twice a week for 56 days.
Results:
Scanning electron microscopy demonstrated that WED prevented and disrupted wound biofilm aggregates. WED accelerated functional wound closure by restoring skin barrier function. WED blunted biofilm-induced expression of (1) P. aeruginosa quorum sensing mvfR (pqsR), rhlR and lasR genes, and (2) miR-9 and silencing of E-cadherin. E-cadherin is critically required for skin barrier function. Furthermore, WED rescued against biofilm-induced persistent inflammation by circumventing nuclear factor kappa B activation and its downstream cytokine responses.
Conclusion:
This is the first pre-clinical porcine mechanistic study to recognize the potential of electroceuticals as an effective platform technology to combat wound biofilm infection.
Objective:
Targeted electrical energy applied to wounds has been shown to improve wound-healing rates. However, the mechanisms are poorly understood. The aim of this study was to identify genes that are responsive to electrical stimulation (ES) in healthy subjects with undamaged skin.
Methods:
To achieve this objective, study authors used a small, noninvasive ES medical device to deliver a continuous, specific, set sequence of electrical energy impulses over a 48-hour period to the skin of healthy volunteers and compared resultant gene expression by microarray analysis.
Main results:
Application of this specific ES resulted in differential expression of 105 genes, the majority of which were down-regulated. Postmicroarray analyses revealed there was commonality with a small number of genes that have previously been shown to be up-regulated in skin wounds, including venous leg ulcers.
Conclusions:
The specific sequence of ES applied continuously for 48 hours to the skin of healthy patients has the effect of modifying expression in a number of identified genes. The identification of the differential expression in this subset of genes in healthy subjects provides new potential lines of scientific inquiry for identifying similar responses in subjects with slow or poorly healing wounds.
Burns are a very painful skin injury, or injury of soft tissues. The development of post-traumatic stress disorder can develop, even in those with minor injuries (Ia–IIb degree). Development of problems is very rapid and intense since, according to developmental embryology, the skin and central nervous system (CNS) descend from the same germ layer—ectoderm.
This clinical report presents the results acquired from the data of 1008 patients suffering from burns treated by the acupuncture (ACU)—from 1983–2015 in the surgery ward of the hospital in Vysoke Myto in the Czech Republic.
The data of 1008 patients were processed and evaluated.
1. The report demonstrates a positive effect of ACU treatment signs on the skin were monitored, i.e. reddening, pigmentation, scars. During the treatment the elimination of many of these signs was observed.
Improvement of healing process and improvement in the final wound healing were evaluated and shown by the statistical method—the χ² test. For demonstrating the effect of ACU treatment of BT the Pearson's and the Cramer's contingency coefficient were examined.
2. The time of the first application of the ACU treatment after burn was followed and evaluated with a random set. The best results were achieved when the first ACU treatment was applied as soon as possible after BT injury (ideally immediately, optimally within 48 h). The positive effect of ACU on burns is medical, economical and biopsychosocial.
Background:
The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention. Chronic conditions such as diabetes mellitus or peripheral vascular disease can lead to impaired wound healing. Acute trauma such as degloving or large-scale thermal injuries are followed by a loss of skin organ function rendering the organism vulnerable to infections, thermal dysregulation, and fluid loss.
Methods:
For this update article, we have reviewed the actual literature on skin wound healing purposes focusing on the main phases of wound healing, i.e., inflammation, proliferation, epithelialization, angiogenesis, remodeling, and scarring.
Results:
The reader will get briefed on new insights and up-to-date concepts in skin wound healing. The macrophage as a key player in the inflammatory phase will be highlighted. During the epithelialization process, we will present the different concepts of how the wound will get closed, e.g., leapfrogging, lamellipodial crawling, shuffling, and the stem cell niche. The neovascularization represents an essential component in wound healing due to its fundamental impact from the very beginning after skin injury until the end of the wound remodeling. Here, the distinct pattern of the neovascularization process and the special new functions of the pericyte will be underscored. At the end, this update will present 3 topics of high interest in skin wound healing issues, dealing with scarring, tissue engineering, and plasma application.
Conclusion:
Although wound healing mechanisms and specific cell functions in wound repair have been delineated in part, many underlying pathophysiological processes are still unknown. The purpose of the following update on skin wound healing is to focus on the different phases and to brief the reader on the current knowledge and new insights. Skin wound healing is a complex process, which is dependent on many cell types and mediators interacting in a highly sophisticated temporal sequence. Although some interactions during the healing process are crucial, redundancy is high and other cells or mediators can adopt functions or signaling without major complications.
The lecture was presented during the Fåhraeus award ceremony for 2016 at the University of Lisbon. It summarizes the main results and some of the more important hemorheological contributions achieved in the Laboratory of Biodynamics and Biorheology of the Institute of Mechanics to BAS and in collaboration with other laboratories of the research group, involved in many studies explaining hemorheological disturbances in various clinical conditions. An original method for the study of microstructural changes in the biological fluids by measuring the electrical conductivity simultaneously with the the rheological properties of red blood cells (RBC) in the whole blood and red blood cell suspensions in a viscometric flow was suggested. The influence of the disturbed hemorheological parameters on the common carotid artery and cerebral blood flow was studied. Analysis of blood flow in the common carotid artery bifurcation with stenosis was done. This lecture does not claim to be a comprehensive review, and many important studies were not cited. The author would like to acknowledge the valuable collaboration of all those cited in the reference list.
Significance
Angiogenesis is essential for the health of all vertebrates, but the outgrowth of new blood vessels also plays a role in disease by facilitating tumorigenesis, boosting inflammation, and causing blindness. Despite intensive investigation, pathological angiogenesis remains a formidable clinical challenge. Here we adopted an experimental strategy focusing on the bioelectric impact of neovascularization. Surprisingly, although the transmembrane voltage of vascular cells is known to regulate blood flow, no previous electrophysiological analysis of pathological angiogenesis has been reported. Using animal models and human specimens of retinal neovascularization, we discovered that neovascular complexes generate an extremely high voltage, whose transmission into the retinovascular network exerts a function-altering impact. Uncovering bioelectric mechanisms in the pathogenesis of neovascularization is likely to reveal new therapeutic targets.
Objective:
This study evaluated the effects of high- (HF) and low-frequency (LF) transcutaneous electrical nerve stimulation on angiogenesis and myofibroblast proliferation in acute excisional wounds in rat skin.
Design:
This was an experimental controlled and randomized study.
Participants:
An excisional wound was made on the back of 90 adult male EPM1-Wistar rats using an 8-mm punch.
Interventions:
The animals were randomly assigned to the HF group (80 Hz), LF group (5 Hz), or control group. Transcutaneous electrical nerve stimulation (pulse duration, 200 microseconds; current amplitude, 15 mA) was delivered (session length, 60 minutes) on 3 consecutive days.
Mean outcome measure:
Immunohistochemistry was performed on postoperative days 3, 7, and 14 for counting blood vessels and myofibroblasts.
Mean outcome results:
The LF group had significantly more blood vessels than the HF group on day 3 (P = .004). The HF group had significantly less blood vessels than did the control group on days 7 (P = .002) and 14 (P = .034) and less myofibroblasts than did both the LF and control groups on day 3 (P = .004) and less than did the control group on day 7 (P = .001).
Conclusion:
There seems to be a benefit to the use of LF transcutaneous electrical nerve stimulation in the healing of acute excisional wounds, but further studies are warranted.
Venous leg ulcer (VLU) is one of the most common lower extremity ulcerated wound, and is a significant healthcare problem with implications that affect social, economic, and the well-being of a patient. VLU can have debilitating related problems which require weekly medical care and may take months to years to heal. The pathophysiology of VLU is complex, and healing is delayed in many patients due to a persistent inflammatory condition. Patient genetic and environmental factors predispose individuals to chronic venous diseases including VLU. Changes in shear stress affecting the glycocalyx are likely initiating events, leading to activation of adhesion molecules on endothelial cells, and leukocyte activation with attachment and migration into vein wall, microcirculation, and in the interstitial space. Multiple chemokines, cytokines, growth factors, proteases and matrix metalloproteinases are produced. The pathology of VLU involves an imbalance of inflammation, inflammatory modulators, oxidative stress, and proteinase activity. Understanding the cellular and biochemical events that lead to the progression of VLU is critical. With further understanding of inflammatory pathways and potential mechanisms, certain biomarkers could be revealed and studied as both involvement in the pathophysiology of VLU but also as therapeutic targets for VLU healing.
Background:
Diabetic foot disease carries a high morbidity and is a leading cause of lower limb amputation. This may in part be due to the effect diabetes mellitus (DM) has on the microcirculation including in the skin.
Method:
We conducted a review of studies that have examined the relationship between microcirculatory function and wound healing in patients with DM. A search of the Medline, Embase, and Web of Science databases was performed coupled with a review of references for the period 1946 to March 2015.
Results:
Nineteen studies of diverse methodology and cohort selection were identified. Poor function of the microcirculation was related to poor outcome. Transcutaneous oxygen pressure (TcPO2) was the most commonly used method to measure the microcirculation and thresholds for poor outcome proposed ranged from 10 mmHg to <34 mmHg. Two studies reexamined microcirculatory function following revascularization. Both found an increase in TcPO2, however only 1 reached statistical significance. No significant difference in the results of microcirculation tests was found between diabetic and nondiabetic patients.
Conclusions:
While it is not possible to draw firm conclusions from the evidence currently available there are clear areas that warrant research. Good microcirculation unsurprisingly appears to associate with better wound healing. The influence of DM is not clear, and neither is the degree of improvement required to achieve healing. Studies that examine a clearly defined cohort both with and without DM are urgently required. Accurate quantitative assessment of microcirculation will aid prediction of wound healing identifying those at greatest risk of amputation.
Data used in Figure 5 (“Focused Doughnut” (FD) pulses) in Papasimakis, N., Fedotov, V.A., Savinov, V., Raybould, T.A. and Zheludev, N.I. (2016) Electromagnetic toroidal excitations in matter and free space. Nature Materials.
The toroidal dipole is a localized electromagnetic excitation independent from the familiar magnetic and electric dipoles. While the electric dipole can be understood as separated opposite charges and the magnetic dipole as a current loop, the toroidal dipole corresponds to currents flowing on the surface of a torus. Resonant interactions of induced toroidal dipoles with electromagnetic waves have recently been observed at microwave, terahertz and optical frequencies. They provide distinct and physically significant contributions to the basic characteristics of matter including absorption, dispersion, and optical activity, the origin of which cannot be comprehensively interpreted in the context of standard multipoles alone.
Interference of radiating induced toroidal and electric dipoles leads to transparency windows in artificial materials as a manifestation of the dynamic anapole. Toroidal excitations also exist in free-space as spatially and temporally localized electromagnetic pulses propagating at the speed of light and interacting with matter.
Diabetes mellitus (DM) is a significant international health concern affecting more than 387 million individuals. A diabetic person has a 25% lifetime risk of developing a diabetic foot ulcer (DFU), leading to limb amputation in up to one in six DFU patients. Low-level light therapy (LLLT) uses low-power lasers or light-emitting diodes to alter cellular function and molecular pathways, and may be a promising treatment for DFU. The goal of this systematic review is to examine whether the clinical use of LLLT is effective in the healing of DFU at 12 weeks and 20 weeks in comparison with the standard of care, and to provide evidence-based recommendation and future clinical guidelines for the treatment of DFU using LLLT. On September 30th 2015, we searched PubMed, EMBASE, CINAHL, and Web of Science databases using the following terms: “diabetic foot” AND “low level light therapy,” OR “light emitting diode,” OR “phototherapy,” OR “laser.” The relevant articles that met the following criteria were selected for inclusion: randomized control trials (RCTs) that investigated the use of LLLT for treatment of DFU. Four RCTs involving 131 participants were suitable for inclusion based upon our criteria. The clinical trials used sham irriadiation, low dose, or non-therapeutic LLLT as placebo or control in comparison to LLLT. The endpoints included ulcer size and time to complete healing with follow-up ranging from 2 weeks to 16 weeks. Each article was assigned a level of evidence (LOE) and graded according to the Oxford Center for Evidence-based Medicine Levels of Evidence Grades of Recommendation criteria. Limitations of reviewed RCTs include a small sample size (N<100), unclear allocation concealment, lack of screening phase to exclude rapid healers, unclear inclusion/exclusion criteria, short (<30 days) follow-up period, and unclear treatment settings (wavelength and treatment time). However, all reviewed RCTs demonstrated therapeutic outcomes with no adverse events using LLLT for treatment of DFU. This systematic review reports that LLLT has significant potential to become a portable, minimally invasive, easy-to-use, and cost effective modality for treatment of DFU. To enthusiastically recommend LLLT for treatment of DFU, additional studies with comparable laser parameters, screening period to exclude rapid healers, larger sample sizes and longer follow-up periods are required. We envision future stringent RCTs may validate LLLT for treatment of DFU. Systematic review registration number: PROSPERO CRD42015029825. This article is protected by copyright. All rights reserved.
Background:
The musculocutaneous flap of the transverse rectus abdominis muscle is a technique used for breast reconstruction, and one of the complications of this procedure is tissue necrosis. The objective of the study is to determine the effect of high-voltage electrical stimulation (HVES) in the transverse rectus abdominis muscle flap in rats.
Methods:
Fourteen rats underwent surgery for obtaining the flap. The rats were distributed into 2 homogeneous groups: group 1 underwent both surgery and the use of HVES, whereas group 2 underwent just the surgery (control). Electrical stimulation was applied immediately after surgery and for 2 consecutive days. The percentage of necrotic area was analyzed using the Image J software, and blood flow was assessed by infrared thermography in different regions of the flap, divided into 4 zones according to the proximity of the pedicle of the inferior epigastric artery.
Results:
The results were analyzed using a Student t test, where group 1 experienced a necrotic area of 26.2%, and group 2 had an area of 54.5%. Regarding the temperature, the 2 groups showed increase in the minimum and maximum temperature on the fourth postoperative day.
Conclusion:
The HVES appeared to have a positive influence on the viability of the flap.